Scientists at the University of Michigan Comprehensive Cancer Center have uncovered an important link between inflammation and breast cancer stem cells that suggests a new way to target cells that are resistant to current treatments.
The researchers identified a receptor, CXCR1, on the cancer stem cells which triggers growth of stem cells in response to inflammation and tissue damage. A drug originally developed to prevent organ transplant rejection blocks this receptor, killing breast cancer stem cells and preventing their metastasis in mice, according to the study.
Cancer stem cells, the small number of cells that fuel a tumor's growth, are believed to be resistant to current chemotherapies and radiation treatment, which researchers say may be the reason cancer so often returns after treatment.
"Developing treatments to effectively target the cancer stem cell population is essential for improving outcomes. This work suggests a new strategy to target cancer stem cells that can be readily translated into the clinic," says senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center. Wicha was part of the team that first identified stem cells in breast cancer.
Results of the current study appear online Jan. 4 in the Journal of Clinical Investigation and will appear in the journal's February print issue.
CXCR1 is a receptor for Interleukin-8, or IL-8, a protein produced during chronic inflammation and tissue injury. When tumors are exposed to chemotherapy, the dying cells produce IL-8, which stimulates cancer stem cells to replicate. Addition of the drug repertaxin to chemotherapy specifically targets and kills breast cancer stem cells by blocking CXCR1.
Mice treated with repertaxin or the combination of repertaxin and chemotherapy had dramatically fewer cancer stem cells than those treated with chemotherapy alone. In addition, repertaxin-treated mice developed significantly fewer metastases than mice treated with chemotherapy alone.
"These studies suggest that important links between inflammation, tissue damage and breast cancer may be mediated by cancer stem cells. Furthermore, anti-inflammatory drugs such as repertaxin may provide a means of blocking these interactions, thereby targeting breast cancer stem cells," Wicha says.
Repertaxin has been tested in early phase clinical trials to prevent rejection after organ transplantation. In these studies, side effects seem to be minimal. There are no reports of using repertaxin to treat cancer.
Notes:
This work was done in cell cultures and mice. Repertaxin is not available to patients at this time and no clinical trials are yet planned.
Breast cancer statisitics: 194,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease, according to the American Cancer Society.
Additional authors: Christophe Ginestier, Suling Liu, Mark Diebel, Hasan Korkaya, Ming Luo, Marty Brown, Jun-Lin Guan, Gabriela Dontu, all from U-M; and Julien Wicinski, Olivier Cabaud, Emmanuelle Charafe-Jauffret, Daniel Birnbaum, all from Universite de la Mediterranee, Marseille, France
Funding: National Institutes of Health, Breast Cancer Foundation, Taubman Institute, Department of Defense, Inserm, Institut Paoli-Calmettes, Institut National du Cancer, Ligue Nationale Contre le Cancer
Disclosure: The University of Michigan has filed for patent protection on this technology, and is currently looking for a commercialization partner to help bring the technology to market.
Reference: Journal of Clinical Investigation, Vol. 120, No. 2, February 2010; doi:10.1172/JCI39397
Source: Nicole Fawcett
University of Michigan Health System
пятница, 27 мая 2011 г.
четверг, 26 мая 2011 г.
Breast, Prostate Cancer Resources Now Available In Spanish
In an effort to reach a greater audience, and help patients and their families understand their cancer treatment options, the American Society for Therapeutic Radiology and Oncology now offers Spanish versions of their popular brochures Radiation Therapy for Breast Cancer and Radiation Therapy for Prostate Cancer.
ASTRO's award-winning patient brochures are part of the public awareness campaign that the Society launched in 2003 to help patients learn more about their treatment options. Although nearly two-thirds of all people living with cancer will receive radiation therapy at some point during their treatment, it is the least understood of the three main cancer treatment modalities, behind surgery and chemotherapy. The new brochures join the growing catalog of patient materials ASTRO has to offer with several of the existing brochures slated for future Spanish translation.
"Trying to understand cancer and the treatments to cure it can be overwhelming for patients and their loved ones," said Thomas J. Eichler, M.D., Chair of ASTRO's Communications Committee and a radiation oncologist at CJW Medical Center at the Thomas Johns Cancer Center in Richmond, Va. "We hope that offering more Spanish language materials will help those grappling with cancer to make well-informed treatment decisions."
The brochures are available free to patients and patient support organizations by visiting ASTRO's patient-dedicated Web site rtanswers. The site also contains more detailed information and pictures explaining how radiation therapy is used to treat cancer and has a "Doctor Finder" feature allowing patients to search for a radiation oncologist by location and specialty.
ASTRO is the largest radiation oncology society in the world, with more than 8,600 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to the advancement of the practice of radiation oncology by promoting excellence in patient care, providing opportunities for educational and professional development, promoting research and disseminating research results and representing radiation oncology in a rapidly evolving socioeconomic healthcare environment.
The American Society for Therapeutic Radiology and Oncology
8280 Willow Oaks Corporate Drive, Suite 500
Fairfax, VA 22031
astro
rtanswers
ASTRO's award-winning patient brochures are part of the public awareness campaign that the Society launched in 2003 to help patients learn more about their treatment options. Although nearly two-thirds of all people living with cancer will receive radiation therapy at some point during their treatment, it is the least understood of the three main cancer treatment modalities, behind surgery and chemotherapy. The new brochures join the growing catalog of patient materials ASTRO has to offer with several of the existing brochures slated for future Spanish translation.
"Trying to understand cancer and the treatments to cure it can be overwhelming for patients and their loved ones," said Thomas J. Eichler, M.D., Chair of ASTRO's Communications Committee and a radiation oncologist at CJW Medical Center at the Thomas Johns Cancer Center in Richmond, Va. "We hope that offering more Spanish language materials will help those grappling with cancer to make well-informed treatment decisions."
The brochures are available free to patients and patient support organizations by visiting ASTRO's patient-dedicated Web site rtanswers. The site also contains more detailed information and pictures explaining how radiation therapy is used to treat cancer and has a "Doctor Finder" feature allowing patients to search for a radiation oncologist by location and specialty.
ASTRO is the largest radiation oncology society in the world, with more than 8,600 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to the advancement of the practice of radiation oncology by promoting excellence in patient care, providing opportunities for educational and professional development, promoting research and disseminating research results and representing radiation oncology in a rapidly evolving socioeconomic healthcare environment.
The American Society for Therapeutic Radiology and Oncology
8280 Willow Oaks Corporate Drive, Suite 500
Fairfax, VA 22031
astro
rtanswers
среда, 25 мая 2011 г.
Predicting Tumors In Women With Common Pre-Breast Cancer
A specific biological response to cellular stress may predict the likelihood of future tumor formation of the most common, non-invasive form of pre-malignant breast cancer-- ductal carcinoma in situ, or DCIS.
This information could potentially be used in a clinical setting to determine which women should receive more or less aggressive therapy when initially diagnosed with DCIS, according to a study led by researchers from the University of California, San Francisco.
The research results are also significant because traditional tests available today are not strong enough to predict whether or not a woman will develop a future cancer after diagnosis with DCIS. By identifying this particular biological response in patients, physicians may now be able to predict subsequent tumor formation years before it actually occurs.
The study is the cover story of the November 13, 2007 issue of Cancer Cell. It is a translational study that brings together an integrated team of basic and clinical scientists in an attempt to find molecular markers to aid women and their physicians in determining the best treatment option following a diagnosis of DCIS.
"We were very excited by the results," said senior author Thea Tlsty, PhD, professor of pathology and co-leader of the Cell Cycling and Signaling Program of the UCSF Comprehensive Cancer Center. "Until now, little has been known about the molecular pathways that may cause a differential risk in women diagnosed with this type of breast pre- malignancy."
DCIS is a type of breast cancer where cancer cells form inside the milk ducts of the breast but have not spread to surrounding breast tissue. DCIS accounts for nearly 25 percent of all breast cancer diagnoses, according to the American Cancer Society.
In the absence of this new information, the researchers said, women diagnosed with DCIS today are often offered a gamut of treatment options that extend from a full mastectomy to watchful waiting. A majority of women usually opt for a lumpectomy with or without additional treatments such as radiation, hormonal therapy or chemotherapy. However, since the majority of DCIS lesions are not associated with formation of subsequent invasive tumors, it is likely that many women diagnosed with DCIS are being over treated.
"Conversely, since some women still get subsequent invasive carcinomas following these therapies, we may be under-treating a group of women diagnosed with DCIS," said Tlsty. Approximately 12-15 percent of women diagnosed with DCIS develop a subsequent invasive tumor within 10 years after undergoing surgical lumpectomy.
As noted in the study, it is well recognized that normal cellular responses to stress are important barriers to cancer formation and therefore also provide researchers with molecular candidates to help identify lesions that will not progress to a malignancy. To determine if stress-associated biomarkers in this response could provide insight into the likelihood of subsequent tumor formation in DCIS, the researchers examined several biomarkers in biopsies of DCIS tissue both in isolation and in conjunction to determine their effects.
They found that the presence of high amounts of two biomarkers, p16 and COX-2, played a critical role in the biological response to cellular stress. In particular, they found that tumors with high p16 and/or high COX-2 in the absence of cell proliferation reflected correct stress activation and a protective response to cellular stress.
"This phenotype begins to identify women less likely to have a subsequent tumor event after a diagnosis of DCIS," said Tlsty. "It supports the hypothesis that the senescent program is a barrier to tumor growth."
In a second group, DCIS tissue with high p16 and/or high COX-2 in the presence of ongoing cell proliferation corresponded to a short-circuited response to cellular stress. The lesions in this group had lost functional p16/retinoblastoma (Rb) signaling, allowing cells to proliferate unchecked and thus likely to lead to subsequent tumor formation. This finding positively identified the Rb pathway as a key regulator in these responses.
Study findings showed that the expression of biomarkers indicative of the short-circuited response was also a defining characteristic of basal-like invasive tumors, a more aggressive form of breast cancer, which was a striking discovery, according to Tlsty.
"We found that the expression of biomarkers of a stress-associated response is conditional and can reflect two distinct processes distinguished by the absence or presence of a proliferation of cells," added Tlsty. "We anticipate that these phenotypes have the potential to accurately predict the occurrence of future tumor events in women diagnosed with DCIS."
The biological phenotypes identified in this study are now being validated in a large, independent study of women diagnosed with DCIS. Initial results are expected within the next year.
This study was supported by the National Cancer Institutes Breast Cancer Specialized Program of Research Excellence (SPORE) grant and the Cancer League.
Study co-leaders were Mona Gauthier, PhD, and Hal Berman, MD, both of the UCSF Department of Pathology, and Karla Kerlikowske, MD, San Francisco VA Medical Center. Additional investigators were Karen Chew, UCSF Comprehensive Cancer Center; Dan Moore, PhD, California Pacific Medical Center; Caroline Miller, Krystyna Kozakiewicz, PhD, Joseph Rabban, MD, and Yunn Yi Chen, MD, PhD all of the UCSF Department of Pathology.
UCSF is a leading university dedicated to defining health worldwide through advanced biomedical research, graduate level education in the life sciences and health professions, and excellence in patient care.
Source: Vanessa deGier
University of California - San Francisco
This information could potentially be used in a clinical setting to determine which women should receive more or less aggressive therapy when initially diagnosed with DCIS, according to a study led by researchers from the University of California, San Francisco.
The research results are also significant because traditional tests available today are not strong enough to predict whether or not a woman will develop a future cancer after diagnosis with DCIS. By identifying this particular biological response in patients, physicians may now be able to predict subsequent tumor formation years before it actually occurs.
The study is the cover story of the November 13, 2007 issue of Cancer Cell. It is a translational study that brings together an integrated team of basic and clinical scientists in an attempt to find molecular markers to aid women and their physicians in determining the best treatment option following a diagnosis of DCIS.
"We were very excited by the results," said senior author Thea Tlsty, PhD, professor of pathology and co-leader of the Cell Cycling and Signaling Program of the UCSF Comprehensive Cancer Center. "Until now, little has been known about the molecular pathways that may cause a differential risk in women diagnosed with this type of breast pre- malignancy."
DCIS is a type of breast cancer where cancer cells form inside the milk ducts of the breast but have not spread to surrounding breast tissue. DCIS accounts for nearly 25 percent of all breast cancer diagnoses, according to the American Cancer Society.
In the absence of this new information, the researchers said, women diagnosed with DCIS today are often offered a gamut of treatment options that extend from a full mastectomy to watchful waiting. A majority of women usually opt for a lumpectomy with or without additional treatments such as radiation, hormonal therapy or chemotherapy. However, since the majority of DCIS lesions are not associated with formation of subsequent invasive tumors, it is likely that many women diagnosed with DCIS are being over treated.
"Conversely, since some women still get subsequent invasive carcinomas following these therapies, we may be under-treating a group of women diagnosed with DCIS," said Tlsty. Approximately 12-15 percent of women diagnosed with DCIS develop a subsequent invasive tumor within 10 years after undergoing surgical lumpectomy.
As noted in the study, it is well recognized that normal cellular responses to stress are important barriers to cancer formation and therefore also provide researchers with molecular candidates to help identify lesions that will not progress to a malignancy. To determine if stress-associated biomarkers in this response could provide insight into the likelihood of subsequent tumor formation in DCIS, the researchers examined several biomarkers in biopsies of DCIS tissue both in isolation and in conjunction to determine their effects.
They found that the presence of high amounts of two biomarkers, p16 and COX-2, played a critical role in the biological response to cellular stress. In particular, they found that tumors with high p16 and/or high COX-2 in the absence of cell proliferation reflected correct stress activation and a protective response to cellular stress.
"This phenotype begins to identify women less likely to have a subsequent tumor event after a diagnosis of DCIS," said Tlsty. "It supports the hypothesis that the senescent program is a barrier to tumor growth."
In a second group, DCIS tissue with high p16 and/or high COX-2 in the presence of ongoing cell proliferation corresponded to a short-circuited response to cellular stress. The lesions in this group had lost functional p16/retinoblastoma (Rb) signaling, allowing cells to proliferate unchecked and thus likely to lead to subsequent tumor formation. This finding positively identified the Rb pathway as a key regulator in these responses.
Study findings showed that the expression of biomarkers indicative of the short-circuited response was also a defining characteristic of basal-like invasive tumors, a more aggressive form of breast cancer, which was a striking discovery, according to Tlsty.
"We found that the expression of biomarkers of a stress-associated response is conditional and can reflect two distinct processes distinguished by the absence or presence of a proliferation of cells," added Tlsty. "We anticipate that these phenotypes have the potential to accurately predict the occurrence of future tumor events in women diagnosed with DCIS."
The biological phenotypes identified in this study are now being validated in a large, independent study of women diagnosed with DCIS. Initial results are expected within the next year.
This study was supported by the National Cancer Institutes Breast Cancer Specialized Program of Research Excellence (SPORE) grant and the Cancer League.
Study co-leaders were Mona Gauthier, PhD, and Hal Berman, MD, both of the UCSF Department of Pathology, and Karla Kerlikowske, MD, San Francisco VA Medical Center. Additional investigators were Karen Chew, UCSF Comprehensive Cancer Center; Dan Moore, PhD, California Pacific Medical Center; Caroline Miller, Krystyna Kozakiewicz, PhD, Joseph Rabban, MD, and Yunn Yi Chen, MD, PhD all of the UCSF Department of Pathology.
UCSF is a leading university dedicated to defining health worldwide through advanced biomedical research, graduate level education in the life sciences and health professions, and excellence in patient care.
Source: Vanessa deGier
University of California - San Francisco
вторник, 24 мая 2011 г.
ARUP Laboratories Announces Availability Of A New Laboratory Developed Test For Subtyping Breast Cancer
ARUP Laboratories, a leading national clinical and anatomic pathology reference laboratory and a leader in innovative laboratory research and development, today announced the availability of a new laboratory developed test designed to classify breast cancer into clinically significant molecular subtypes that are important for the management of the disease.
The new test is a RT-qPCR assay that measures the expression of 50 classifier genes and five control genes to identify the intrinsic subtypes known as Luminal A, Luminal B, HER2-enriched and Basal-like. Along with a categorical classification of breast cancer subtype, it also provides quantitative values for proliferation, luminal gene expression, ESR1, PGR and ERBB2. The test is listed in ARUP Laboratories' Laboratory Test Directory (LTD) as the PAM50 Breast Cancer Intrinsic Classifier™.
The PAM50 test offered by ARUP is the first clinical iteration of this gene expression signature, which has already been extensively validated in the research setting. "Although many gene sets have been used as surrogates for biologic subtyping of breast cancer, the PAM50 has proven to be a more accurate predictor of patient outcome than standard methods," said Philip Bernard, MD, medical director for the Molecular Pathology Laboratory at ARUP Laboratories and a co-inventor of the new assay.
The development of the PAM50 signature was the culmination of a decade of work that became a multi-institutional project with investigators from the University of Utah (Dr. Philip Bernard), the University of North Carolina at Chapel Hill (Dr. Charles Perou), the University of British Columbia (Dr. Torsten Nielsen), and the Washington University School of Medicine in St. Louis (Dr. Matthew Ellis).
Standard methods for diagnosing and treating breast cancer include anatomic staging, histological assessment, and molecular testing for ER, PR and HER2/neu protein expression. The PAM50 test is performed from formalin-fixed, paraffin-embedded tissues so that specimens are handled within routine clinical practice. "Having additional information about the tumor biology and quantitative data on biomarkers already used for treatment decisions is the first step towards personalized health care in oncology," said Bernard.
The PAM50 is the beginning of a suite of multi-analyte gene expression oncology tests offered by ARUP Laboratories and is complemented by other mutation tests (e.g., EGFR, KRAS and PIK3CA) that are already available.
"Our goal at ARUP Laboratories has always been to improve the quality and efficacy of medical care by providing accurate and actionable information derived from diagnostic laboratory tests," said Sherrie Perkins, MD, PhD, chief medical officer and director of laboratories at ARUP Laboratories. "This test represents our efforts to promote the right test for the right patient at the right time."
Source:
ARUP Laboratories
The new test is a RT-qPCR assay that measures the expression of 50 classifier genes and five control genes to identify the intrinsic subtypes known as Luminal A, Luminal B, HER2-enriched and Basal-like. Along with a categorical classification of breast cancer subtype, it also provides quantitative values for proliferation, luminal gene expression, ESR1, PGR and ERBB2. The test is listed in ARUP Laboratories' Laboratory Test Directory (LTD) as the PAM50 Breast Cancer Intrinsic Classifier™.
The PAM50 test offered by ARUP is the first clinical iteration of this gene expression signature, which has already been extensively validated in the research setting. "Although many gene sets have been used as surrogates for biologic subtyping of breast cancer, the PAM50 has proven to be a more accurate predictor of patient outcome than standard methods," said Philip Bernard, MD, medical director for the Molecular Pathology Laboratory at ARUP Laboratories and a co-inventor of the new assay.
The development of the PAM50 signature was the culmination of a decade of work that became a multi-institutional project with investigators from the University of Utah (Dr. Philip Bernard), the University of North Carolina at Chapel Hill (Dr. Charles Perou), the University of British Columbia (Dr. Torsten Nielsen), and the Washington University School of Medicine in St. Louis (Dr. Matthew Ellis).
Standard methods for diagnosing and treating breast cancer include anatomic staging, histological assessment, and molecular testing for ER, PR and HER2/neu protein expression. The PAM50 test is performed from formalin-fixed, paraffin-embedded tissues so that specimens are handled within routine clinical practice. "Having additional information about the tumor biology and quantitative data on biomarkers already used for treatment decisions is the first step towards personalized health care in oncology," said Bernard.
The PAM50 is the beginning of a suite of multi-analyte gene expression oncology tests offered by ARUP Laboratories and is complemented by other mutation tests (e.g., EGFR, KRAS and PIK3CA) that are already available.
"Our goal at ARUP Laboratories has always been to improve the quality and efficacy of medical care by providing accurate and actionable information derived from diagnostic laboratory tests," said Sherrie Perkins, MD, PhD, chief medical officer and director of laboratories at ARUP Laboratories. "This test represents our efforts to promote the right test for the right patient at the right time."
Source:
ARUP Laboratories
понедельник, 23 мая 2011 г.
Phase III Trial Will Study Efficacy Of Incorporating Mind-Body Intervention Into Breast Cancer Treatment, Cost-Benefit And Work Productivity
In an ongoing effort to scientifically validate the age-old belief that mind-body interventions have a beneficial impact on the health of patients, The University of Texas M. D. Anderson Cancer Center has been awarded more than $4.5 million to study the efficacy of incorporating yoga into the treatment program of women with breast cancer.
The grant, the largest ever awarded by the National Cancer Institute for the study of yoga in cancer, will allow researchers to conduct a Phase III clinical trial in women with breast cancer to determine the improvement in physical function and quality-of-life during and after radiation treatment. It will also investigate if such stress reduction programs result in economic and/or work productivity benefit.
Lorenzo Cohen, Ph.D., professor and director of M. D. Anderson's integrative medicine program, received the funding.
"Research has shown that yoga and other types of mind-body practices, incorporated into the standard of care, can help improve patient outcomes, particularly quality-of-life," said Cohen, the study's principal investigator. "However, none have become standard of care, or are on the clinical care pathway for cancer patients. This funding will allow us to definitively determine the benefit of incorporating yoga into treatment plan for women with breast cancer."
The research is being done in collaboration with the Vivekananda Yoga Anusandhana Samsthana (VYASA), a yoga research foundation and university in Bangalore, India. M. D. Anderson has been collaboration with VYASA for more than six years.
Two previous studies led by Cohen and colleagues investigating yoga in similar populations of breast cancer patients have shown benefits in physical function, compared to women who did simple stretching and/or those who did not participate in any such program. Patients who participated in the yoga program reported that their ability to engage in everyday activities - walking a flight of stairs or around the block, carrying a bag of groceries - all improved, said Cohen. The study also found an indication of improved sleep and reduced fatigue levels, and preliminary analysis suggests lowered stress hormone levels in the yoga group.
Building on such research, the Phase III study will enroll 600 women with stage 0-3 breast cancer, all undergoing radiation at M. D. Anderson. The women will be randomized to one of three groups: yoga (YG), stretching/relaxation (STR) or those who receive the standard of care and do not enroll in any exercise program, the waitlist control (WLC). Participants in both the yoga and stretching groups will attend sessions three days a week throughout their six weeks of radiation.
Participants will self-report quality-of-life aspects, including physical function, mental health and fatigue levels. In addition to reporting their sleep quality, patients also will wear an activity watch monitor that objectively monitors the restfulness of their sleep. Cortisol levels will also be collected and studied, as blunted cortisol slopes have been linked to worse outcomes in breast cancer, said Cohen.
A secondary aim of the trial, but one of great importance, stressed Cohen, is assessing cost efficiency analysis for the hospital, and health care utilization costs in general, as well as examining work productivity of patients.
"In this age of health care reform, it's very important to determine the cost savings, not only to the hospital, but to also to women's lives and their ability to engage in their work in a productive fashion, whether that's the work of being a mother and running a household or working outside the home," said Cohen. "By including such data as cost-effectiveness analyses, we may be able to change the standard of care the way women with breast cancer are treated in this country."
Source:
Laura Sussman
University of Texas M. D. Anderson Cancer Center
The grant, the largest ever awarded by the National Cancer Institute for the study of yoga in cancer, will allow researchers to conduct a Phase III clinical trial in women with breast cancer to determine the improvement in physical function and quality-of-life during and after radiation treatment. It will also investigate if such stress reduction programs result in economic and/or work productivity benefit.
Lorenzo Cohen, Ph.D., professor and director of M. D. Anderson's integrative medicine program, received the funding.
"Research has shown that yoga and other types of mind-body practices, incorporated into the standard of care, can help improve patient outcomes, particularly quality-of-life," said Cohen, the study's principal investigator. "However, none have become standard of care, or are on the clinical care pathway for cancer patients. This funding will allow us to definitively determine the benefit of incorporating yoga into treatment plan for women with breast cancer."
The research is being done in collaboration with the Vivekananda Yoga Anusandhana Samsthana (VYASA), a yoga research foundation and university in Bangalore, India. M. D. Anderson has been collaboration with VYASA for more than six years.
Two previous studies led by Cohen and colleagues investigating yoga in similar populations of breast cancer patients have shown benefits in physical function, compared to women who did simple stretching and/or those who did not participate in any such program. Patients who participated in the yoga program reported that their ability to engage in everyday activities - walking a flight of stairs or around the block, carrying a bag of groceries - all improved, said Cohen. The study also found an indication of improved sleep and reduced fatigue levels, and preliminary analysis suggests lowered stress hormone levels in the yoga group.
Building on such research, the Phase III study will enroll 600 women with stage 0-3 breast cancer, all undergoing radiation at M. D. Anderson. The women will be randomized to one of three groups: yoga (YG), stretching/relaxation (STR) or those who receive the standard of care and do not enroll in any exercise program, the waitlist control (WLC). Participants in both the yoga and stretching groups will attend sessions three days a week throughout their six weeks of radiation.
Participants will self-report quality-of-life aspects, including physical function, mental health and fatigue levels. In addition to reporting their sleep quality, patients also will wear an activity watch monitor that objectively monitors the restfulness of their sleep. Cortisol levels will also be collected and studied, as blunted cortisol slopes have been linked to worse outcomes in breast cancer, said Cohen.
A secondary aim of the trial, but one of great importance, stressed Cohen, is assessing cost efficiency analysis for the hospital, and health care utilization costs in general, as well as examining work productivity of patients.
"In this age of health care reform, it's very important to determine the cost savings, not only to the hospital, but to also to women's lives and their ability to engage in their work in a productive fashion, whether that's the work of being a mother and running a household or working outside the home," said Cohen. "By including such data as cost-effectiveness analyses, we may be able to change the standard of care the way women with breast cancer are treated in this country."
Source:
Laura Sussman
University of Texas M. D. Anderson Cancer Center
воскресенье, 22 мая 2011 г.
BSI-201 Enters Phase III In Metastatic Triple Negative Breast Cancer
Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) and its wholly owned subsidiary, BiPar Sciences, announced the initiation of the pivotal Phase III trial for BSI-201 in combination with chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC), defined by tumors lacking expression of estrogen, progesterone receptors and without over-expression of HER2. BSI-201 is a novel investigational targeted therapy which inhibits poly (ADP-ribose) polymerase (PARP1), an enzyme involved in DNA damage repair.
The Phase III trial is a multi-center, randomized trial designed to evaluate the safety and efficacy of BSI-201 when combined with gemcitabine and carboplatin (GC) in women with mTNBC. A total of 420 mTNBC patients, who have received 0-2 prior therapies in the metastatic setting, will be randomized to receive GC with or without BSI-201.
The co-primary objectives of this study are to assess improvement in progression-free survival and overall survival. The secondary objectives are to assess objective response rate and safety. An estimated 60-75 sites will be distributed throughout the United States. Importantly, this trial will have a crossover provision that will ensure that all patients enrolled in the BSI-201 Phase III clinical trial have the potential opportunity to receive BSI-201 (patients randomly assigned to the control arm may receive BSI-201 upon disease progression).
The decision to commence with the Phase III study was made based on Phase II study results presented during the Plenary Session of the American Society of Clinical Oncology (ASCO) annual conference on May 31, 2009. The randomized Phase II clinical trial involved 116 women with metastatic TNBC who were randomly assigned to receive GC in combination with the investigational agent BSI-201 or GC alone.
Approximately 62 percent of patients receiving BSI-201 in combination with GC showed clinical benefit, compared with 21 percent in the group receiving chemotherapy alone (p= 0.0002). Tumor response (complete or partial response) was observed in 48 percent of patients who received BSI-201 combined with chemotherapy, whereas patients receiving chemotherapy alone showed a response rate of 16 percent. Women who received BSI-201 had a median progression-free survival of 6.9 months and overall survival of 9.2 months compared with 3.3 and 5.7 months, respectively, for women who received chemotherapy alone. The hazard ratios for progression-free survival and overall survival were 0.342 (p< 0.0001) and 0.348 (p=0.0005), respectively.
The most common severe (grades 3 and 4) side effects included neutropenia [25/57 in patients treated with GC and BSI-201; 31/59 patients treated with GC alone], thrombocytopenia and anemia. No febrile neutropenia was observed in patients receiving BSI-201 combined with chemotherapy. BSI-201 did not add to the frequency or severity of adverse events associated with chemotherapy.
About BSI-201
Among other investigational PARP inhibitors in the industry, BSI-201 is the furthest along in clinical development in metastatic TNBC. BSI-201 is currently being evaluated for its potential to enhance the effect of chemotherapy-induced DNA damage.
About TNBC
When patients are diagnosed with breast cancer, their tumors are routinely tested for the presence of estrogen and progesterone receptors and for the over-expression of HER2. Commonly used breast cancer therapies target these receptors; for example, tamoxifen for estrogen receptor and trastuzumab (Herceptin®) for HER2. However, 15-20 percent of all breast cancers lack over-expression of all three proteins, thus giving rise to the term "triple-negative breast cancer" or "TNBC."
TNBC can be an aggressive disease, with higher rates of metastases and poorer survival rates than other breast cancer subtypes. No treatment has been approved specifically for TNBC.
About BiPar Sciences
BiPar Sciences is a biopharmaceutical organization pioneering novel tumor-selective therapies designed to address urgent unmet needs of cancer patients. In addition to BSI-201, the company also has two additional compounds in preclinical development. BiPar Sciences, located in South San Francisco, California, is a wholly owned subsidiary of sanofi-aventis.
About Sanofi Aventis
Sanofi-aventis is a leading global pharmaceutical company that discovers, develops and distributes therapeutic solutions to help improve the lives of patients. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include product development, product potential projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMEA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such products candidates, the absence of guarantee that the products candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives as well as those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2008. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.
Source: Sanofi Aventis
View drug information on Herceptin.
The Phase III trial is a multi-center, randomized trial designed to evaluate the safety and efficacy of BSI-201 when combined with gemcitabine and carboplatin (GC) in women with mTNBC. A total of 420 mTNBC patients, who have received 0-2 prior therapies in the metastatic setting, will be randomized to receive GC with or without BSI-201.
The co-primary objectives of this study are to assess improvement in progression-free survival and overall survival. The secondary objectives are to assess objective response rate and safety. An estimated 60-75 sites will be distributed throughout the United States. Importantly, this trial will have a crossover provision that will ensure that all patients enrolled in the BSI-201 Phase III clinical trial have the potential opportunity to receive BSI-201 (patients randomly assigned to the control arm may receive BSI-201 upon disease progression).
The decision to commence with the Phase III study was made based on Phase II study results presented during the Plenary Session of the American Society of Clinical Oncology (ASCO) annual conference on May 31, 2009. The randomized Phase II clinical trial involved 116 women with metastatic TNBC who were randomly assigned to receive GC in combination with the investigational agent BSI-201 or GC alone.
Approximately 62 percent of patients receiving BSI-201 in combination with GC showed clinical benefit, compared with 21 percent in the group receiving chemotherapy alone (p= 0.0002). Tumor response (complete or partial response) was observed in 48 percent of patients who received BSI-201 combined with chemotherapy, whereas patients receiving chemotherapy alone showed a response rate of 16 percent. Women who received BSI-201 had a median progression-free survival of 6.9 months and overall survival of 9.2 months compared with 3.3 and 5.7 months, respectively, for women who received chemotherapy alone. The hazard ratios for progression-free survival and overall survival were 0.342 (p< 0.0001) and 0.348 (p=0.0005), respectively.
The most common severe (grades 3 and 4) side effects included neutropenia [25/57 in patients treated with GC and BSI-201; 31/59 patients treated with GC alone], thrombocytopenia and anemia. No febrile neutropenia was observed in patients receiving BSI-201 combined with chemotherapy. BSI-201 did not add to the frequency or severity of adverse events associated with chemotherapy.
About BSI-201
Among other investigational PARP inhibitors in the industry, BSI-201 is the furthest along in clinical development in metastatic TNBC. BSI-201 is currently being evaluated for its potential to enhance the effect of chemotherapy-induced DNA damage.
About TNBC
When patients are diagnosed with breast cancer, their tumors are routinely tested for the presence of estrogen and progesterone receptors and for the over-expression of HER2. Commonly used breast cancer therapies target these receptors; for example, tamoxifen for estrogen receptor and trastuzumab (Herceptin®) for HER2. However, 15-20 percent of all breast cancers lack over-expression of all three proteins, thus giving rise to the term "triple-negative breast cancer" or "TNBC."
TNBC can be an aggressive disease, with higher rates of metastases and poorer survival rates than other breast cancer subtypes. No treatment has been approved specifically for TNBC.
About BiPar Sciences
BiPar Sciences is a biopharmaceutical organization pioneering novel tumor-selective therapies designed to address urgent unmet needs of cancer patients. In addition to BSI-201, the company also has two additional compounds in preclinical development. BiPar Sciences, located in South San Francisco, California, is a wholly owned subsidiary of sanofi-aventis.
About Sanofi Aventis
Sanofi-aventis is a leading global pharmaceutical company that discovers, develops and distributes therapeutic solutions to help improve the lives of patients. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include product development, product potential projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMEA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such products candidates, the absence of guarantee that the products candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives as well as those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2008. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.
Source: Sanofi Aventis
View drug information on Herceptin.
суббота, 21 мая 2011 г.
No Association Between Estrogen, Lung Cancer Incidence And Mortality Among Postmenopausal Women
Use of estrogen alone did not increase lung cancer mortality in postmenopausal women, according to a study published online in The Journal of the National Cancer Institute.
In the Women's Health Initiative (WHI) trial, which consisted of several clinical trials on postmenopausal women, one study showed women with previous hysterectomy taking combined estrogen plus progestin therapy had a statistically significant increase in lung cancer mortality, but not incidence. Other studies with combined hormone therapy have had conflicting results. But the influence of estrogen alone was unclear.
To determine whether use of estrogen alone was associated with lung cancer incidence and increased lung cancer mortality, Rowan T. Chlebowski, M.D., Ph.D., of the Los Angeles Biomedical Research Institute, and colleagues, in a post-hoc analysis examined data from a previous randomized, double-blind, placebo-controlled trial in the WHI. This trial was conducted in 40 centers in the U.S., in which 10,739 postmenopausal women aged 50-79 years with a hysterectomy were randomly assigned to groups receiving estrogen alone or placebo.
The researchers found there was only one more death from lung cancer in the estrogen group (34 deaths) compared with the placebo group (33 deaths). Their conclusion was that use of estrogen alone was not associated with lung cancer incidence or death from lung cancer in women with hysterectomies.
The researchers also found that although the effects of combined estrogen and progestin and estrogen alone on coronary heart disease were similar, there were differences in the two therapies' effect on various types of cancer. Combined therapy showed a statistically significant increase of breast cancer incidence, whereas estrogen alone showed a reduced incidence. However, combined therapy showed a statistically significant reduction in colorectal cancer, whereas estrogen alone was not associated with colorectal cancer.
The authors say that a limitation of the study was the small sample size and that further investigation comparing combined therapy to estrogen alone is needed. However, they write, "These findings should be reassuring for women with previous hysterectomy, who use estrogen alone for climacteric symptom management."
Source:
Kristine Crane
Journal of the National Cancer Institute
In the Women's Health Initiative (WHI) trial, which consisted of several clinical trials on postmenopausal women, one study showed women with previous hysterectomy taking combined estrogen plus progestin therapy had a statistically significant increase in lung cancer mortality, but not incidence. Other studies with combined hormone therapy have had conflicting results. But the influence of estrogen alone was unclear.
To determine whether use of estrogen alone was associated with lung cancer incidence and increased lung cancer mortality, Rowan T. Chlebowski, M.D., Ph.D., of the Los Angeles Biomedical Research Institute, and colleagues, in a post-hoc analysis examined data from a previous randomized, double-blind, placebo-controlled trial in the WHI. This trial was conducted in 40 centers in the U.S., in which 10,739 postmenopausal women aged 50-79 years with a hysterectomy were randomly assigned to groups receiving estrogen alone or placebo.
The researchers found there was only one more death from lung cancer in the estrogen group (34 deaths) compared with the placebo group (33 deaths). Their conclusion was that use of estrogen alone was not associated with lung cancer incidence or death from lung cancer in women with hysterectomies.
The researchers also found that although the effects of combined estrogen and progestin and estrogen alone on coronary heart disease were similar, there were differences in the two therapies' effect on various types of cancer. Combined therapy showed a statistically significant increase of breast cancer incidence, whereas estrogen alone showed a reduced incidence. However, combined therapy showed a statistically significant reduction in colorectal cancer, whereas estrogen alone was not associated with colorectal cancer.
The authors say that a limitation of the study was the small sample size and that further investigation comparing combined therapy to estrogen alone is needed. However, they write, "These findings should be reassuring for women with previous hysterectomy, who use estrogen alone for climacteric symptom management."
Source:
Kristine Crane
Journal of the National Cancer Institute
пятница, 20 мая 2011 г.
Recurring Mutation Found In Breast, Colorectal And Ovarian Cancers That May Alter Tumor Cell Proliferation
Researchers from Eli Lilly & Company and the Phoenix-based Translational Genomics Research Institute (TGen) have announced finding a novel recurring mutation of the gene AKT1 in breast, colorectal and ovarian cancers. The altered form of AKT1 appears to cause tumor cell proliferation and may play a role in making cells resistant to certain types of therapies. The findings are reported in an advance online publication (AOP) of the journal Nature.
The PI3-Kinase/AKT pathway is among the most commonly activated cellular pathways in human cancers and members of this pathway are among the most frequently targeted for new cancer drug discovery efforts. Activation of this pathway results in cancer cell growth and cell survival. Although AKT1 is central to pathway activation, its role in cancer has been that of an intermediary between mutated upstream regulatory proteins and downstream survival signaling proteins. This is the first evidence of direct mutation of AKT1 in human cancer tumors: it was discovered in clinical samples from cancer patients, yet has never been detected in cancer cell lines.
"This discovery is a seminal finding in cancer biology that confirms AKT1 as an oncogene in breast, colorectal and ovarian cancer. The mutation alters the electrostatics of binding pocket in the pleckstrin homology domain, the portion of the enzyme that docks with phospholipids on the cell membrane," said Kerry L. Blanchard, PhD, MD, Executive Director, Discovery Biology Research, Eli Lilly & Company.
To identify the AKT1 mutation, the researchers analyzed 150 tumor samples from patients with either breast, colorectal or ovarian cancer (50 samples from each tumor type). Analysis of the data showed that 8 percent of breast, 6 percent of colorectal and 2 percent of ovarian tumors had the AKT1 mutation in the samples that were screened in their study.
"Recently, molecular features such as the AKT1 mutation are beginning to change drug development efforts. This discovery adds to the short but growing list of molecular features that may help guide both current and future cancer drug development," said John Carpten, PhD, Senior Investigator and Director of TGen's Integrated Cancer Genomics Division and the study's lead author. "The next step is to determine the prevalence of the AKT1 mutation in different populations and, hopefully, use the information gained to stratify patients going into clinical trials for AKT inhibitors."
If validated by further studies, the identification of this recurring mutation has the potential to impact cancer treatment and drug development.
"This is a gorgeous study that used a variety of sophisticated techniques to provide new insights into the tumorigenic process," said Bert Vogelstein, MD, Director of the Ludwig Center for Cancer Genetics & Therapeutics at The Johns Hopkins Kimmel Cancer Center.
James E. Thomas, PhD, of Lilly's Cancer Discovery Research division, explained, "AKT1 is a protein kinase or enzyme that plays a key role in activating survival, proliferation and metabolic pathways. Interestingly, other cellular proteins that regulate this network have also been shown to be mutated in a variety of cancers including lung, breast ovary, prostate, colorectal and brain cancers. This mutation in AKT1 is striking direct evidence for the role of AKT1 in cancer formation."
The identification of the AKT1 mutation was a collaborative effort between Eli Lilly & Company and TGen. "This discovery demonstrates the importance of studying the genetic make up of cancers at the clinical level rather than relying on model systems," adds Jeffrey Trent, PhD, Scientific Director of TGen.
"This is a key study highlighting Lilly's commitment to translational research approaches in cancer drug discovery and development. Furthermore, this work is a great example of a successful public-private partnership at a global level that involves Lilly Research Laboratories in Indianapolis, TGen in Phoenix, Lilly Singapore Centre for Drug Discovery, and the Economic Development Board of Singapore", adds Richard Gaynor, MD, Vice President of Oncology Discovery at Eli Lilly & Company. He added, "This mutation further validates AKT1 as an attractive drug target, and it also will be a valuable tool for the stratification of patients for targeted therapies. This paradigm of identifying specific defects in cancer cells to successfully develop innovative therapies has been validated with oncology drugs such as Gleevec in leukemia and Herceptin in breast cancer."
About Lilly
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers -- through medicines and information -- for some of the world's most urgent medical needs. Additional information about Lilly is available at lilly/.
About TGen
The Translational Genomics Research Institute (TGen), a non-profit 501(c)(3) organization, is focused on developing earlier diagnoses and smarter treatments. Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project and applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. TGen's research is based on personalized medicine and the institute plans to accomplish its goals through robust and disease-focused research. tgen/
Source: Amy Erickson
The Translational Genomics Research Institute
View drug information on Gleevec; Herceptin.
The PI3-Kinase/AKT pathway is among the most commonly activated cellular pathways in human cancers and members of this pathway are among the most frequently targeted for new cancer drug discovery efforts. Activation of this pathway results in cancer cell growth and cell survival. Although AKT1 is central to pathway activation, its role in cancer has been that of an intermediary between mutated upstream regulatory proteins and downstream survival signaling proteins. This is the first evidence of direct mutation of AKT1 in human cancer tumors: it was discovered in clinical samples from cancer patients, yet has never been detected in cancer cell lines.
"This discovery is a seminal finding in cancer biology that confirms AKT1 as an oncogene in breast, colorectal and ovarian cancer. The mutation alters the electrostatics of binding pocket in the pleckstrin homology domain, the portion of the enzyme that docks with phospholipids on the cell membrane," said Kerry L. Blanchard, PhD, MD, Executive Director, Discovery Biology Research, Eli Lilly & Company.
To identify the AKT1 mutation, the researchers analyzed 150 tumor samples from patients with either breast, colorectal or ovarian cancer (50 samples from each tumor type). Analysis of the data showed that 8 percent of breast, 6 percent of colorectal and 2 percent of ovarian tumors had the AKT1 mutation in the samples that were screened in their study.
"Recently, molecular features such as the AKT1 mutation are beginning to change drug development efforts. This discovery adds to the short but growing list of molecular features that may help guide both current and future cancer drug development," said John Carpten, PhD, Senior Investigator and Director of TGen's Integrated Cancer Genomics Division and the study's lead author. "The next step is to determine the prevalence of the AKT1 mutation in different populations and, hopefully, use the information gained to stratify patients going into clinical trials for AKT inhibitors."
If validated by further studies, the identification of this recurring mutation has the potential to impact cancer treatment and drug development.
"This is a gorgeous study that used a variety of sophisticated techniques to provide new insights into the tumorigenic process," said Bert Vogelstein, MD, Director of the Ludwig Center for Cancer Genetics & Therapeutics at The Johns Hopkins Kimmel Cancer Center.
James E. Thomas, PhD, of Lilly's Cancer Discovery Research division, explained, "AKT1 is a protein kinase or enzyme that plays a key role in activating survival, proliferation and metabolic pathways. Interestingly, other cellular proteins that regulate this network have also been shown to be mutated in a variety of cancers including lung, breast ovary, prostate, colorectal and brain cancers. This mutation in AKT1 is striking direct evidence for the role of AKT1 in cancer formation."
The identification of the AKT1 mutation was a collaborative effort between Eli Lilly & Company and TGen. "This discovery demonstrates the importance of studying the genetic make up of cancers at the clinical level rather than relying on model systems," adds Jeffrey Trent, PhD, Scientific Director of TGen.
"This is a key study highlighting Lilly's commitment to translational research approaches in cancer drug discovery and development. Furthermore, this work is a great example of a successful public-private partnership at a global level that involves Lilly Research Laboratories in Indianapolis, TGen in Phoenix, Lilly Singapore Centre for Drug Discovery, and the Economic Development Board of Singapore", adds Richard Gaynor, MD, Vice President of Oncology Discovery at Eli Lilly & Company. He added, "This mutation further validates AKT1 as an attractive drug target, and it also will be a valuable tool for the stratification of patients for targeted therapies. This paradigm of identifying specific defects in cancer cells to successfully develop innovative therapies has been validated with oncology drugs such as Gleevec in leukemia and Herceptin in breast cancer."
About Lilly
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers -- through medicines and information -- for some of the world's most urgent medical needs. Additional information about Lilly is available at lilly/.
About TGen
The Translational Genomics Research Institute (TGen), a non-profit 501(c)(3) organization, is focused on developing earlier diagnoses and smarter treatments. Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project and applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. TGen's research is based on personalized medicine and the institute plans to accomplish its goals through robust and disease-focused research. tgen/
Source: Amy Erickson
The Translational Genomics Research Institute
View drug information on Gleevec; Herceptin.
четверг, 19 мая 2011 г.
Avastin(R) (bevacizumab) Now Approved For Use In Combination With Docetaxel For The First Line Treatment Of Metastatic Breast Cancer, UK
More patients with metastatic breast cancer could benefit from Avastin (bevacizumab) as a result of a broader label announced by the European Commission that allows bevacizumab to be combined with either docetaxel or paclitaxel chemotherapy1. This is an important announcement, as although bevacizumab has been approved for use in the UK in combination with paclitaxel for the treatment of metastatic breast cancer since March 2007, a higher proportion of metastatic breast cancer patients in the UK are treated with docetaxel.
This new licence extension provides physicians who may have used docetaxel alone to treat their metastatic breast cancer patients with an additional treatment option - the data for which show that half of patients were alive without their disease progressing for at least 10 months when treated with bevacizumab plus docetaxel (compared to 8 months with docetaxel alone). Nearly two thirds of patients (64%) receiving bevacizumab-based therapy also experienced major shrinkage in their tumour2. These data re-enforce previous findings that show bevacizumab in addition to paclitaxel increased progression free survival to 11.3 months compared to 5.8 months with paclitaxel alone3.
'Bevacizumab is changing the way cancer is treated, and it has already demonstrated significant benefits across multiple tumour types including breast cancer,' said William M. Burns, CEO of Roche's Pharmaceuticals Division. 'This approval is positive news as more patients with advanced breast cancer could benefit from bevacizumab since physicians will now have more treatment options.'
Breast cancer is the most common cancer in the UK (excluding non-melanoma skin cancer) and the treatment aims for metastatic breast cancer are to control rather than cure the disease; prolong life, improve symptoms and maintain quality of life4. Despite earlier diagnosis and the treatment improvements that have already been made, there are still around 12,000 breast cancer deaths in the UK each year4.
Bevacizumab has a well-established tolerability profile and the most frequently observed drug reactions in clinical trials were hypertension, fatigue, neuropathy and proteinuria. Bevacizumab does not markedly increase chemotherapy-related toxicities, and the most common side effects are generally manageable.
About AVADO (BO17708)2
AVADO is an international phase III trial where 736 patients who did not receive previous chemotherapy for their metastatic breast cancer were randomised to one of three treatment groups:
- Bevacizumab 15 mg/kg every 3 weeks in combination with docetaxel 100 mg/m2
- Bevacizumab 7.5 mg/kg every 3 weeks in combination with docetaxel 100 mg/m2
- Placebo in combination with docetaxel 100 mg/m2 as control arm
The primary objective of the study was to demonstrate superiority in progression free survival in one or both of bevacizumab containing treatment arms compared to the control arm. Secondary endpoints for the study included response rate, duration of response, time to treatment failure, overall survival, 1-year survival, quality of life, safety and tolerability. Based on the updated analysis the combination of bevacizumab and docetaxel resulted in:
- Nearly two thirds of patients (64%) receiving bevacizumab based therapy experienced major shrinkage in their tumour.
- Half the patients were alive without their disease progressing for more than 10 months when treated with bevacizumab plus docetaxel compared to 8 months with docetaxel alone.
- In the 1-year survival analysis there were significantly more patients alive when treated with bevacizumab + docetaxel (84%) compared to docetaxel alone (76%).
- Overall survival data, reflecting ~ 45% of events, show no difference between the treatment arms.
- No new safety signals, confirming the safety and tolerability profile seen in previous studies. Furthermore, bevacizumab had only a limited impact on the known toxicity profile of docetaxel.
About Avastin (bevacizumab)
Avastin is an antibody that specifically binds and blocks VEGF (vascular endothelial growth factor). VEGF is the key driver of tumour angiogenesis - an essential process of development and maintenance of blood vessels which is required for a tumour to grow and to spread (metastasize) to other parts of the body. Avastin's precise mode of action helps control tumour growth and metastases with only a limited impact on side effects of chemotherapy.
Bevacizumab has now demonstrated a progression-free and/or overall survival benefit for patients in four types of metastatic/advanced cancer: colorectal, breast cancer, lung and renal cell cancer.
Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of bevacizumab in various tumour types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma and others) and different settings (advanced and adjuvant i.e. post-operation). The total development programme is expected to include over 40,000 patients worldwide.
References
1. CHMP bevacizumab metastatic breast cancer positive opinion 29 July 2009
2. Roche Products Ltd, Data on File BO17708 001/09.
3. Cameron D. Bevacizumab in the first-line treatment of metastatic breast cancer. European journal of cancer, supplement, 2008, 6: 21-8
4. Cancer Research UK - Breast cancer - UK accessed on 29 July 2009
Source
Roche
View drug information on Avastin.
This new licence extension provides physicians who may have used docetaxel alone to treat their metastatic breast cancer patients with an additional treatment option - the data for which show that half of patients were alive without their disease progressing for at least 10 months when treated with bevacizumab plus docetaxel (compared to 8 months with docetaxel alone). Nearly two thirds of patients (64%) receiving bevacizumab-based therapy also experienced major shrinkage in their tumour2. These data re-enforce previous findings that show bevacizumab in addition to paclitaxel increased progression free survival to 11.3 months compared to 5.8 months with paclitaxel alone3.
'Bevacizumab is changing the way cancer is treated, and it has already demonstrated significant benefits across multiple tumour types including breast cancer,' said William M. Burns, CEO of Roche's Pharmaceuticals Division. 'This approval is positive news as more patients with advanced breast cancer could benefit from bevacizumab since physicians will now have more treatment options.'
Breast cancer is the most common cancer in the UK (excluding non-melanoma skin cancer) and the treatment aims for metastatic breast cancer are to control rather than cure the disease; prolong life, improve symptoms and maintain quality of life4. Despite earlier diagnosis and the treatment improvements that have already been made, there are still around 12,000 breast cancer deaths in the UK each year4.
Bevacizumab has a well-established tolerability profile and the most frequently observed drug reactions in clinical trials were hypertension, fatigue, neuropathy and proteinuria. Bevacizumab does not markedly increase chemotherapy-related toxicities, and the most common side effects are generally manageable.
About AVADO (BO17708)2
AVADO is an international phase III trial where 736 patients who did not receive previous chemotherapy for their metastatic breast cancer were randomised to one of three treatment groups:
- Bevacizumab 15 mg/kg every 3 weeks in combination with docetaxel 100 mg/m2
- Bevacizumab 7.5 mg/kg every 3 weeks in combination with docetaxel 100 mg/m2
- Placebo in combination with docetaxel 100 mg/m2 as control arm
The primary objective of the study was to demonstrate superiority in progression free survival in one or both of bevacizumab containing treatment arms compared to the control arm. Secondary endpoints for the study included response rate, duration of response, time to treatment failure, overall survival, 1-year survival, quality of life, safety and tolerability. Based on the updated analysis the combination of bevacizumab and docetaxel resulted in:
- Nearly two thirds of patients (64%) receiving bevacizumab based therapy experienced major shrinkage in their tumour.
- Half the patients were alive without their disease progressing for more than 10 months when treated with bevacizumab plus docetaxel compared to 8 months with docetaxel alone.
- In the 1-year survival analysis there were significantly more patients alive when treated with bevacizumab + docetaxel (84%) compared to docetaxel alone (76%).
- Overall survival data, reflecting ~ 45% of events, show no difference between the treatment arms.
- No new safety signals, confirming the safety and tolerability profile seen in previous studies. Furthermore, bevacizumab had only a limited impact on the known toxicity profile of docetaxel.
About Avastin (bevacizumab)
Avastin is an antibody that specifically binds and blocks VEGF (vascular endothelial growth factor). VEGF is the key driver of tumour angiogenesis - an essential process of development and maintenance of blood vessels which is required for a tumour to grow and to spread (metastasize) to other parts of the body. Avastin's precise mode of action helps control tumour growth and metastases with only a limited impact on side effects of chemotherapy.
Bevacizumab has now demonstrated a progression-free and/or overall survival benefit for patients in four types of metastatic/advanced cancer: colorectal, breast cancer, lung and renal cell cancer.
Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of bevacizumab in various tumour types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma and others) and different settings (advanced and adjuvant i.e. post-operation). The total development programme is expected to include over 40,000 patients worldwide.
References
1. CHMP bevacizumab metastatic breast cancer positive opinion 29 July 2009
2. Roche Products Ltd, Data on File BO17708 001/09.
3. Cameron D. Bevacizumab in the first-line treatment of metastatic breast cancer. European journal of cancer, supplement, 2008, 6: 21-8
4. Cancer Research UK - Breast cancer - UK accessed on 29 July 2009
Source
Roche
View drug information on Avastin.
среда, 18 мая 2011 г.
HER-2 Status Predicts Success Of Chemotherapy In Breast Cancer Treatment
Researchers have found they can potentially target chemotherapy for breast cancer to only those women most likely to benefit, sparing the majority of patients from unnecessary side effects.
The multicenter study, led by University of Michigan Comprehensive Cancer Center researchers, found women whose breast cancer expressed a protein called HER-2 were most likely to benefit from adding the drug Taxol to the chemotherapy regimen, while women whose tumors were fueled by estrogen but did not express HER-2 did not get any benefit from the added Taxol. About 15 percent to 20 percent of breast cancers express HER-2, and as many as three-quarters of breast cancers are so-called estrogen-receptor-positive.
Results of the study appear in the Oct. 11 issue of the New England Journal of Medicine.
"In general, chemotherapy for breast cancer has been a one-size-fits-all approach. Our decision to recommend it is based on whether a woman is at high risk of the breast cancer recurring, without any idea of whether she would benefit from the additional therapy. With this data we hope we will be able to focus chemotherapy on patients whom it's most likely to help," says lead study author Daniel Hayes, M.D., clinical director of the breast oncology program at the U-M Comprehensive Cancer Center. Hayes was the lead investigator on the study, which was run by the Cancer and Leukemia Group B through the Breast Cancer Intergroup of North America.
The study looked at tissue samples and data from 1,500 women who had previously participated in a study looking at the benefit of adding Taxol after four cycles of the drugs Adriamycin and Cytoxan, so-called AC chemotherapy. Cancer had spread to the lymph nodes in all of the women, which is a standard indication to recommend chemotherapy. All the women were given AC chemotherapy for four cycles, after which half the women received four cycles of Taxol and the other half did not receive any more chemotherapy. A previous analysis had shown that adding Taxol decreased the chances of cancer recurring and improved survival when all patients were considered, with no consideration of HER-2 status.
But, previous studies have also suggested that women whose tumors were estrogen-receptor-positive did not seem to benefit as much from chemotherapy as those women whose tumors do not need estrogen.
In this recent analysis, researchers found that the addition of Taxol improved survival rates in women who were HER-2-positive, regardless of their estrogen receptor status. But women whose tumors were HER-2-negative and estrogen-receptor-positive had no additional benefit from the Taxol. More than half of the patients in the study fell into this category.
The researchers do not recommend a change in treatment at this point, stating that more research must be done to confirm that Taxol does not benefit estrogen-receptor-positive breast cancer.
"This is the first such observation that's been made, and it was made retrospectively, meaning we looked backwards instead of forwards. We are not recommending at this time that women with positive lymph nodes, for whom we would currently recommend Taxol, but who are estrogen receptor positive and HER-2 negative not take the Taxol. We think the stakes are too high," Hayes says.
"We've seen mortality from breast cancer dropping in recently years because we've applied these new and better therapies. But now we believe, if these results are confirmed and validated in other studies, that perhaps we could pull out half the patients in that study and save them from the toxicities and the cost of receiving a drug that might not do them any good," he continues.
Doctors have been able to use newer drugs, such as tamoxifen, aromatase inhibitors or Herceptin, to treat only some women with breast cancer, based on whether their tumor expresses estrogen receptor or HER-2. But this method of targeting treatment had not been possible with traditional chemotherapy. This new study suggests doctors might be able to consider estrogen receptor status and HER-2 status together to determine what treatment will be most effective, sparing some women from the toxic side effects of drugs that are not likely to be effective.
"Determining who doesn't need chemotherapy and can be spared some portion of toxic therapy is one of the biggest issues facing breast cancer today," says senior study author Donald Berry, Ph.D., professor and head of the Division of Quantitative Sciences at The University of Texas M. D. Anderson Cancer Center. "In oncology, we are very good at adding therapies to a patient's regimen, but we are not as confident subtracting treatment. Hopefully, in time, we'll be able to limit therapies to those that will truly benefit from the additional regimen."
In addition to Hayes and Berry, study authors were Ann Thor, M.D., from the University of Colorado; Lynn Dressler, Dr.Ph., David Cowan and Susan Edgerton all from the University of North Carolina, Chapel Hill; Donald Weaver, M.D., from the University of Vermont; Gloria Broadwater, Duke University; Lori Goldstein, M.D., from Fox Chase Comprehensive Cancer Center; Silvana Martino, D.O., from the Angeles Clinic and Research Institute; James Ingle, M.D., from the Mayo clinic; I. Craig Henderson, M.D., from the University of California at San Francisco; Larry Norton, M.D., and Clifford Hudis, M.D., both from Memorial Sloan-Kettering Cancer Center; Eric Winer, M.D., from the Dana-Farber Cancer Institute; and Matthew Ellis, Ph.D., from Washington University.
Funding for the study was from the National Institutes of Health, the Breast Cancer Research Foundation, the National Cancer Institute and the Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale.
Note for patients: The researchers are not suggesting a change in recommended treatment based on these study results. Patients with questions about their specific treatment should consult their oncologists. For general questions about breast cancer treatment options, call the U-M Cancer AnswerLine at 800-865-1125.
Reference: New England Journal of Medicine, Vol. 357, No. 15, pp. 1496-1506
University of Michigan Health System
2901 Hubbard St., Ste. 2400
Ann Arbor, MI 48109-2435
United States
med.umich
View drug information on Herceptin; Taxol.
The multicenter study, led by University of Michigan Comprehensive Cancer Center researchers, found women whose breast cancer expressed a protein called HER-2 were most likely to benefit from adding the drug Taxol to the chemotherapy regimen, while women whose tumors were fueled by estrogen but did not express HER-2 did not get any benefit from the added Taxol. About 15 percent to 20 percent of breast cancers express HER-2, and as many as three-quarters of breast cancers are so-called estrogen-receptor-positive.
Results of the study appear in the Oct. 11 issue of the New England Journal of Medicine.
"In general, chemotherapy for breast cancer has been a one-size-fits-all approach. Our decision to recommend it is based on whether a woman is at high risk of the breast cancer recurring, without any idea of whether she would benefit from the additional therapy. With this data we hope we will be able to focus chemotherapy on patients whom it's most likely to help," says lead study author Daniel Hayes, M.D., clinical director of the breast oncology program at the U-M Comprehensive Cancer Center. Hayes was the lead investigator on the study, which was run by the Cancer and Leukemia Group B through the Breast Cancer Intergroup of North America.
The study looked at tissue samples and data from 1,500 women who had previously participated in a study looking at the benefit of adding Taxol after four cycles of the drugs Adriamycin and Cytoxan, so-called AC chemotherapy. Cancer had spread to the lymph nodes in all of the women, which is a standard indication to recommend chemotherapy. All the women were given AC chemotherapy for four cycles, after which half the women received four cycles of Taxol and the other half did not receive any more chemotherapy. A previous analysis had shown that adding Taxol decreased the chances of cancer recurring and improved survival when all patients were considered, with no consideration of HER-2 status.
But, previous studies have also suggested that women whose tumors were estrogen-receptor-positive did not seem to benefit as much from chemotherapy as those women whose tumors do not need estrogen.
In this recent analysis, researchers found that the addition of Taxol improved survival rates in women who were HER-2-positive, regardless of their estrogen receptor status. But women whose tumors were HER-2-negative and estrogen-receptor-positive had no additional benefit from the Taxol. More than half of the patients in the study fell into this category.
The researchers do not recommend a change in treatment at this point, stating that more research must be done to confirm that Taxol does not benefit estrogen-receptor-positive breast cancer.
"This is the first such observation that's been made, and it was made retrospectively, meaning we looked backwards instead of forwards. We are not recommending at this time that women with positive lymph nodes, for whom we would currently recommend Taxol, but who are estrogen receptor positive and HER-2 negative not take the Taxol. We think the stakes are too high," Hayes says.
"We've seen mortality from breast cancer dropping in recently years because we've applied these new and better therapies. But now we believe, if these results are confirmed and validated in other studies, that perhaps we could pull out half the patients in that study and save them from the toxicities and the cost of receiving a drug that might not do them any good," he continues.
Doctors have been able to use newer drugs, such as tamoxifen, aromatase inhibitors or Herceptin, to treat only some women with breast cancer, based on whether their tumor expresses estrogen receptor or HER-2. But this method of targeting treatment had not been possible with traditional chemotherapy. This new study suggests doctors might be able to consider estrogen receptor status and HER-2 status together to determine what treatment will be most effective, sparing some women from the toxic side effects of drugs that are not likely to be effective.
"Determining who doesn't need chemotherapy and can be spared some portion of toxic therapy is one of the biggest issues facing breast cancer today," says senior study author Donald Berry, Ph.D., professor and head of the Division of Quantitative Sciences at The University of Texas M. D. Anderson Cancer Center. "In oncology, we are very good at adding therapies to a patient's regimen, but we are not as confident subtracting treatment. Hopefully, in time, we'll be able to limit therapies to those that will truly benefit from the additional regimen."
In addition to Hayes and Berry, study authors were Ann Thor, M.D., from the University of Colorado; Lynn Dressler, Dr.Ph., David Cowan and Susan Edgerton all from the University of North Carolina, Chapel Hill; Donald Weaver, M.D., from the University of Vermont; Gloria Broadwater, Duke University; Lori Goldstein, M.D., from Fox Chase Comprehensive Cancer Center; Silvana Martino, D.O., from the Angeles Clinic and Research Institute; James Ingle, M.D., from the Mayo clinic; I. Craig Henderson, M.D., from the University of California at San Francisco; Larry Norton, M.D., and Clifford Hudis, M.D., both from Memorial Sloan-Kettering Cancer Center; Eric Winer, M.D., from the Dana-Farber Cancer Institute; and Matthew Ellis, Ph.D., from Washington University.
Funding for the study was from the National Institutes of Health, the Breast Cancer Research Foundation, the National Cancer Institute and the Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale.
Note for patients: The researchers are not suggesting a change in recommended treatment based on these study results. Patients with questions about their specific treatment should consult their oncologists. For general questions about breast cancer treatment options, call the U-M Cancer AnswerLine at 800-865-1125.
Reference: New England Journal of Medicine, Vol. 357, No. 15, pp. 1496-1506
University of Michigan Health System
2901 Hubbard St., Ste. 2400
Ann Arbor, MI 48109-2435
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View drug information on Herceptin; Taxol.
вторник, 17 мая 2011 г.
Circulating Tumor Cells Prove To Be Key Predictors of Survival in Newly Diagnosed Metastatic Breast Cancer Patients
Homogenous test group reinforces value of information gleaned through simple blood test -
Veridex LLC, a Johnson & Johnson company, today announced that a study published in the Journal of Clinical Oncology (March
1, 2005) found that the presence of circulating tumor cells (CTCs) in the blood of patients newly diagnosed with metastatic
breast cancer is highly predictive of progression-free, overall survival, and is associated with significant prognostic
information. Further, the results indicate that the company's CellSearch™ System, which was used to identify and enumerate
CTCs - cancer cells that detach from solid tumors and enter the bloodstream - may one day allow for design of tailored
treatments earlier than ever before possible.
Researchers worked with an 83-patient subset of the 177 patients with metastatic breast cancer who were involved in a
multi-institution, double blind study recently published in The New England Journal of Medicine (August 19, 2004). In order
to obtain the most directly comparable results possible, the subset was limited to patients whose cancer had recurred but who
had not yet received any treatment, thereby eliminating complicating factors such as differences among prior therapies, or
stage and timing of treatments. Patients were tested for a CTC count prior to initial therapy, then approximately every four
weeks and were followed clinically out to 18 months.
Patients with five or more CTCs per 7.5mL (the equivalent of one blood draw) at baseline and first follow-up (four weeks)
ultimately had significantly shorter progression-free survival and overall survival. Patients with five or more CTC had a
median PFS of 4.9 months and a median OS of 14.2 months OS prior to the administration of therapy versus patients with fewer
than five CTCs prior to therapy (median PFS of 9.5 months and more than 18 months OS). At first follow-up after the
administration of the first cycle of therapy, patients with five or more CTC had a median PFS of 2.1 months and 11.1 months
OS versus patients with less than five CTC had median PFS of 8.9 months and more than 18 months OS.
"By studying a subpopulation of patients who are at precisely the same point in their illness, without having to take into
account a variety of outside factors, we could have a clear picture of the biology of metastatic breast cancer and the role
that CTCs played," said lead author Massimo Cristofanilli, M.D., associate professor in the Department of Medical Oncology at
the University of Texas M. D. Anderson Cancer Center. "Our findings with this homogenous group of patients reinforce the
value of this technology in identifying patients who might be resistant to a particular therapy and those who could benefit
from early treatment change or a more investigational approach."
The CellSearch™ Circulating Tumor Cell Test requires only a simple blood draw from a patient, but its sensitivity and
specificity allow physicians to observe true changes in CTCs that are greater than or less than the five CTC cutoff. This
information may help physicians predict, with a high degree of certainty, progression-free and overall survival in individual
patients both before and following a single cycle of therapy, develop individual patient treatment strategies and counsel and
advise patients appropriately.
"Scientists have long believed that circulating tumor cells held a wealth of information, but there was no method to
efficiently and objectively evaluate and utilize them for decision making in routine medical practice," said Robert T.
McCormack, Ph.D., general manager, Cellular Diagnostics for Veridex, LLC. "We're pleased that this study has shown that our
technology will go a long way toward addressing an unmet need in the cancer field and could change the course of treatment
for many critically ill patients."
Immunicon Corp., of Huntingdon Valley, PA, developed the CellSearch™ System under a Development, License and Supply Agreement
with Veridex, LLC.
About Veridex, LLC
Veridex, LLC, a Johnson & Johnson company, develops cancer diagnostic products that will enable earlier disease detection as
well as more accurate staging, monitoring and therapeutic selection. The company is initially developing two complementary
product lines: CellSearch™ assays that identify, enumerate and characterize circulating tumor cells directly from whole
blood; and GeneSearch™ assays that use molecular technology to diagnose, stage and more accurately characterize tumors. For
more information, visit veridex.
Veridex LLC, a Johnson & Johnson company, today announced that a study published in the Journal of Clinical Oncology (March
1, 2005) found that the presence of circulating tumor cells (CTCs) in the blood of patients newly diagnosed with metastatic
breast cancer is highly predictive of progression-free, overall survival, and is associated with significant prognostic
information. Further, the results indicate that the company's CellSearch™ System, which was used to identify and enumerate
CTCs - cancer cells that detach from solid tumors and enter the bloodstream - may one day allow for design of tailored
treatments earlier than ever before possible.
Researchers worked with an 83-patient subset of the 177 patients with metastatic breast cancer who were involved in a
multi-institution, double blind study recently published in The New England Journal of Medicine (August 19, 2004). In order
to obtain the most directly comparable results possible, the subset was limited to patients whose cancer had recurred but who
had not yet received any treatment, thereby eliminating complicating factors such as differences among prior therapies, or
stage and timing of treatments. Patients were tested for a CTC count prior to initial therapy, then approximately every four
weeks and were followed clinically out to 18 months.
Patients with five or more CTCs per 7.5mL (the equivalent of one blood draw) at baseline and first follow-up (four weeks)
ultimately had significantly shorter progression-free survival and overall survival. Patients with five or more CTC had a
median PFS of 4.9 months and a median OS of 14.2 months OS prior to the administration of therapy versus patients with fewer
than five CTCs prior to therapy (median PFS of 9.5 months and more than 18 months OS). At first follow-up after the
administration of the first cycle of therapy, patients with five or more CTC had a median PFS of 2.1 months and 11.1 months
OS versus patients with less than five CTC had median PFS of 8.9 months and more than 18 months OS.
"By studying a subpopulation of patients who are at precisely the same point in their illness, without having to take into
account a variety of outside factors, we could have a clear picture of the biology of metastatic breast cancer and the role
that CTCs played," said lead author Massimo Cristofanilli, M.D., associate professor in the Department of Medical Oncology at
the University of Texas M. D. Anderson Cancer Center. "Our findings with this homogenous group of patients reinforce the
value of this technology in identifying patients who might be resistant to a particular therapy and those who could benefit
from early treatment change or a more investigational approach."
The CellSearch™ Circulating Tumor Cell Test requires only a simple blood draw from a patient, but its sensitivity and
specificity allow physicians to observe true changes in CTCs that are greater than or less than the five CTC cutoff. This
information may help physicians predict, with a high degree of certainty, progression-free and overall survival in individual
patients both before and following a single cycle of therapy, develop individual patient treatment strategies and counsel and
advise patients appropriately.
"Scientists have long believed that circulating tumor cells held a wealth of information, but there was no method to
efficiently and objectively evaluate and utilize them for decision making in routine medical practice," said Robert T.
McCormack, Ph.D., general manager, Cellular Diagnostics for Veridex, LLC. "We're pleased that this study has shown that our
technology will go a long way toward addressing an unmet need in the cancer field and could change the course of treatment
for many critically ill patients."
Immunicon Corp., of Huntingdon Valley, PA, developed the CellSearch™ System under a Development, License and Supply Agreement
with Veridex, LLC.
About Veridex, LLC
Veridex, LLC, a Johnson & Johnson company, develops cancer diagnostic products that will enable earlier disease detection as
well as more accurate staging, monitoring and therapeutic selection. The company is initially developing two complementary
product lines: CellSearch™ assays that identify, enumerate and characterize circulating tumor cells directly from whole
blood; and GeneSearch™ assays that use molecular technology to diagnose, stage and more accurately characterize tumors. For
more information, visit veridex.
понедельник, 16 мая 2011 г.
Breast Radiation Exposure Reduced By 50 Percent Using Angled Gantry Technique
A novel angled gantry approach to coronary CT angiography reduced radiation exposure to the breast by more than 50%, according to Thomas Jefferson University researchers.
Ethan Halpern, M.D., associate professor of Radiology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, presented the research at the 94th Scientific Assembly and Annual Meeting of the Radiological Society of North America.
"Radiation dose to the breast during coronary CT is especially a concern for young women as the dose may increase the risk for breast cancer," Dr. Halpern said. "Physicians are working diligently to reduce the patient radiation dose related to coronary CT."
Dr. Halpern and colleagues retrospectively reviewed 100 consecutive coronary CT angiography images that were obtained with a 64 detector helical scanner. They evaluated sagital images to: 1) define the position of the breasts and the gantry angulation required to perform a CT examination parallel to the long axis of the heart; and 2) determine the reduction in breast exposure to radiation that might be accomplished by imaging the heart with an angled gantry acquisition.
The standard axial imaging plane for coronary CT angiography required a 6.5cm. В± 1.8 cm. overlap with the lower breast. The overlap with the lower breast using the angled scan was reduced in half to 3.2 cm В± 1.6 cm (P
Ethan Halpern, M.D., associate professor of Radiology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, presented the research at the 94th Scientific Assembly and Annual Meeting of the Radiological Society of North America.
"Radiation dose to the breast during coronary CT is especially a concern for young women as the dose may increase the risk for breast cancer," Dr. Halpern said. "Physicians are working diligently to reduce the patient radiation dose related to coronary CT."
Dr. Halpern and colleagues retrospectively reviewed 100 consecutive coronary CT angiography images that were obtained with a 64 detector helical scanner. They evaluated sagital images to: 1) define the position of the breasts and the gantry angulation required to perform a CT examination parallel to the long axis of the heart; and 2) determine the reduction in breast exposure to radiation that might be accomplished by imaging the heart with an angled gantry acquisition.
The standard axial imaging plane for coronary CT angiography required a 6.5cm. В± 1.8 cm. overlap with the lower breast. The overlap with the lower breast using the angled scan was reduced in half to 3.2 cm В± 1.6 cm (P
воскресенье, 15 мая 2011 г.
American Cancer Society Plans To Shift Message About Benefits Of Screening For Breast, Other Cancers
The American Cancer Society is working to modify its message about screenings for breast and prostate cancers to say that the benefits of early detection might have been overstated, the New York Times reports. According to the Times, the new message will caution that screenings can lead to overtreatment of small cancers while overlooking potentially deadly cancers.
The cancer society's decision to reconsider its message about the risks and benefits of screening was in part spurred by an analysis published Wednesday in the Journal of the American Medical Association . Authors Laura Esserman of the University of California-San Francisco's Carol Frank Buck Breast Cancer Center and Ian Thompson of the Department of Urology at the University of Texas Health Science Center reported that a 40% increase in breast cancer diagnoses and a nearly 100% increase in early-stage cancers have coincided with just a 10% decline in cancers that have spread to the lymph nodes or to other parts of the body. According to the analysis, screenings are contributing to huge increases in breast and prostate cancer diagnoses because they are finding innocuous tumors that have no risk of spreading and do not necessarily require treatment. The key is to distinguish between those tumors that are innocuous and those that need aggressive treatment. The analysis noted that if screenings were really as beneficial as they are promised to be, the significant increase in detection of early cancers would correspond to a massive decline in late-stage cancers -- which has been the case for colon and cervical cancer screenings but not for breast or prostate cancers.
ACS chief medical officer Otis Brawley said, "The issue here is, as we look at cancer medicine over the last 35 or 40 years, we have always worked to treat cancer or to find cancer early," but "we never sat back and actually thought, 'Are we treating the cancers that need to be treated?'" Barnett Kramer, associate director for disease prevention at NIH, said that the notion that some cancers are not dangerous and could go away on their own is "so counterintuitive that it raises debate every time it comes up and every time it has been observed." According to Kramer, "Overdiagnosis is pure, unadulterated harm."
However, the researchers don't believe that screening should go away - but that people should better understand the risks and benefits. ACS plans to revamp its screening message on its Web site next year. Currently, the site states that a mammogram is "one of the best things a woman can do to protect her health." Brawley said, "We don't want people to panic." However, he added, "I'm admitting that American medicine has overpromised when it comes to screening. The advantages to screening have been exaggerated" (Kolata, New York Times, 10/21).
Reprinted with kind permission from nationalpartnership. You can view the entire Daily Women's Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women's Health Policy Report is a free service of the National Partnership for Women & Families, published by The Advisory Board Company.
© 2009 The Advisory Board Company. All rights reserved.
суббота, 14 мая 2011 г.
Department Of Health And Children Statement On Misdiagnosis Of Breast Cancer, Ireland
The Minister for Health and Children, Mary Harney, TD, was made aware in recent days by the HSE about the misdiagnosis of breast cancer in a woman who resides in the Mid-Western region. She is aware that the woman presented to Barrington's Hospital, Limerick, initially in 2005, and again in 2007, and that there is specific concern surrounding two pathology tests performed in University College Hospital, Galway during that time.
The Minister apologises to this woman and her family for the distress and trauma caused to them.
The Minister has decided that a prompt investigation is required into all aspects of this woman's care, and any other issues that may arise, in line with best international practice following reports of adverse clinical events. She has asked officials to examine the most appropriate and effective mechanism for this investigation, including the option of a statutory inquiry under the Commissions of Investigations Act, 2004, which would require Government approval.
She also intends that the Medical Council be fully briefed on the circumstances surrounding this case and to request it to examine relevant aspects under its own statutory powers.
Role of HIQA
The powers of the recently established Health Information and Quality Authority (HIQA) extend to publicly-provided services. HIQA is, therefore, in a position to undertake an inquiry only into the components of this woman's care provided in HSE-funded institutions.
The Minister has consulted with HIQA on how a prompt and wide ranging review of all aspects of this woman's care, including those components provided in the independent hospital sector can be progressed. She plans to draw on the expertise of HIQA to advise on and support any resulting process.
HIQA is taking part in the Commission on Patient Safety, established by the Minister in January and chaired by Dr Deirdre Madden. Its work, which has an 18 month timeframe, includes developing proposals for greater accountability within our health system for performance in relation to patient safety, more effective reporting of adverse clinical events and complaints in order to learn from them, and a statutory system of licensing of all providers of health care.
The best advice made available to the Minister has been that a licensing system for independent providers should be in place in order for HIQA to carry out investigations into non-publicly-funded health care provision.
Standards for Breast Cancer Care
In May this year, the Minister approved "Quality Assurance Standards for Symptomatic Breast Disease Services in Ireland", which were prepared by a multi-disciplinary expert group and submitted to the Minister by HIQA. The Minister accepts the strong advice of HIQA and the expert group that care provided in accordance with these standards enhances quality reduces the likelihood of clinical errors and improves a woman's chance of surviving her cancer and maximising her quality of life.
These standards require significant reorganisation of breast cancer services to ensure that each centre providing breast cancer care
-- Manages a minimum of 150 new cases each year
-- Ensures that such care is provided by a team made up of a surgeon, a radiologist and a pathologist
-- Has a minimum of three consultants in each of these specialties
The Department of Health and Children has asked the HSE to progress the full and prompt implementation of these standards. HIQA will monitor and review the HSE's implementation of these standards and report directly to the Minister.
The Minister calls on hospitals in the independent sector and on the organisations that fund and insure care in that sector to take immediate steps to ensure that breast cancer services provided in non-HSE funded institutions are in compliance with these standards.
dohc.ie
The Minister apologises to this woman and her family for the distress and trauma caused to them.
The Minister has decided that a prompt investigation is required into all aspects of this woman's care, and any other issues that may arise, in line with best international practice following reports of adverse clinical events. She has asked officials to examine the most appropriate and effective mechanism for this investigation, including the option of a statutory inquiry under the Commissions of Investigations Act, 2004, which would require Government approval.
She also intends that the Medical Council be fully briefed on the circumstances surrounding this case and to request it to examine relevant aspects under its own statutory powers.
Role of HIQA
The powers of the recently established Health Information and Quality Authority (HIQA) extend to publicly-provided services. HIQA is, therefore, in a position to undertake an inquiry only into the components of this woman's care provided in HSE-funded institutions.
The Minister has consulted with HIQA on how a prompt and wide ranging review of all aspects of this woman's care, including those components provided in the independent hospital sector can be progressed. She plans to draw on the expertise of HIQA to advise on and support any resulting process.
HIQA is taking part in the Commission on Patient Safety, established by the Minister in January and chaired by Dr Deirdre Madden. Its work, which has an 18 month timeframe, includes developing proposals for greater accountability within our health system for performance in relation to patient safety, more effective reporting of adverse clinical events and complaints in order to learn from them, and a statutory system of licensing of all providers of health care.
The best advice made available to the Minister has been that a licensing system for independent providers should be in place in order for HIQA to carry out investigations into non-publicly-funded health care provision.
Standards for Breast Cancer Care
In May this year, the Minister approved "Quality Assurance Standards for Symptomatic Breast Disease Services in Ireland", which were prepared by a multi-disciplinary expert group and submitted to the Minister by HIQA. The Minister accepts the strong advice of HIQA and the expert group that care provided in accordance with these standards enhances quality reduces the likelihood of clinical errors and improves a woman's chance of surviving her cancer and maximising her quality of life.
These standards require significant reorganisation of breast cancer services to ensure that each centre providing breast cancer care
-- Manages a minimum of 150 new cases each year
-- Ensures that such care is provided by a team made up of a surgeon, a radiologist and a pathologist
-- Has a minimum of three consultants in each of these specialties
The Department of Health and Children has asked the HSE to progress the full and prompt implementation of these standards. HIQA will monitor and review the HSE's implementation of these standards and report directly to the Minister.
The Minister calls on hospitals in the independent sector and on the organisations that fund and insure care in that sector to take immediate steps to ensure that breast cancer services provided in non-HSE funded institutions are in compliance with these standards.
dohc.ie
пятница, 13 мая 2011 г.
Medifocus Inc. Announces That It Has Received Approval For Its Amended Phase III Clinical Trial For Treatment Of Breast Cancer From Health Canada
Medifocus Inc. (OTC:MDFZF.PK and TSXV:MFS) is pleased to announce that it has received approval from Health Canada to amend its pivotal Phase III study design and clinical protocol to conform to the study design and clinical protocol as approved by the Food and Drug Administration (FDA) in the USA for the Company's pivotal Phase III clinical trial on treatment of breast cancer. Medifocus received the full Investigational Testing Authorization (ITA) from Health Canada to initiate the pivotal Phase III trial in Canada in June 2009 and also received the Investigational Device Exemption to initiate the same pivotal trial in the USA from the FDA in March, 2010.
Medifocus' pivotal Phase III clinical trial design is based on results from four (4) clinical studies performed in the USA with the Company's Microfocus APA 1000 Breast Cancer Thermotherapy System. The patient data leading to the design of the pivotal trial were summarized and published online on December 22, 2009 in the journal Annals of Surgical Oncology. The article is titled "Focused Microwave Thermotherapy for Preoperative Treatment of Invasive Breast Cancer: A Review of Clinical Studies" by William C. Dooley, MD, Hernan I. Vargas, MD, Alan J. Fenn, PhD, Mary Beth Tomaselli, MD, and Jay K. Harness, MD.
As summarized in the above mentioned review article, the clinical data showed that when the Medifocus focused heat treatment was used in combination with the Standard of Care (SoC) chemotherapy, the median tumor shrinkage in the thermo-chemotherapy arm was 88.4% while for chemotherapy alone, the median tumor shrinkage was only 58.8%. This increase in median tumor shrinkage was statistically significant with a P value equal to 0.048. In addition, the data indicated that for the thermo-chemotherapy treatment arm, almost 80% of all breast tumors treated had a tumor volume reduction of 80% or more compared to only 20% for the chemotherapy alone arm. The Company's focused heat treatment, once commercialized, may be in a position to help these patients to improve their chance of breast conservation thus reducing the need for mastectomy.
The pivotal Phase III clinical trial is designed to assess the safety and improvement in efficacy, as measured by increased tumor shrinkage, using the Company's focused microwave heat energy in combination with neo-adjuvant (pre-operative) chemotherapy over chemotherapy alone on large breast cancer tumors. A total of 238 patients will be entered into the pivotal study at six medical institutions in the USA and Canada as approved by the FDA. Institutional Review Board (IRB) approval will be required at the participating USA medical institutions.
This Health Canada approval allows the Company to conduct the USA and Canada studies simultaneously using the same study design and clinical protocol, so that patient data obtained from both USA and Canada can be shared and used towards obtaining commercial approval for the system from both countries
Source
Medifocus, Inc.
Medifocus' pivotal Phase III clinical trial design is based on results from four (4) clinical studies performed in the USA with the Company's Microfocus APA 1000 Breast Cancer Thermotherapy System. The patient data leading to the design of the pivotal trial were summarized and published online on December 22, 2009 in the journal Annals of Surgical Oncology. The article is titled "Focused Microwave Thermotherapy for Preoperative Treatment of Invasive Breast Cancer: A Review of Clinical Studies" by William C. Dooley, MD, Hernan I. Vargas, MD, Alan J. Fenn, PhD, Mary Beth Tomaselli, MD, and Jay K. Harness, MD.
As summarized in the above mentioned review article, the clinical data showed that when the Medifocus focused heat treatment was used in combination with the Standard of Care (SoC) chemotherapy, the median tumor shrinkage in the thermo-chemotherapy arm was 88.4% while for chemotherapy alone, the median tumor shrinkage was only 58.8%. This increase in median tumor shrinkage was statistically significant with a P value equal to 0.048. In addition, the data indicated that for the thermo-chemotherapy treatment arm, almost 80% of all breast tumors treated had a tumor volume reduction of 80% or more compared to only 20% for the chemotherapy alone arm. The Company's focused heat treatment, once commercialized, may be in a position to help these patients to improve their chance of breast conservation thus reducing the need for mastectomy.
The pivotal Phase III clinical trial is designed to assess the safety and improvement in efficacy, as measured by increased tumor shrinkage, using the Company's focused microwave heat energy in combination with neo-adjuvant (pre-operative) chemotherapy over chemotherapy alone on large breast cancer tumors. A total of 238 patients will be entered into the pivotal study at six medical institutions in the USA and Canada as approved by the FDA. Institutional Review Board (IRB) approval will be required at the participating USA medical institutions.
This Health Canada approval allows the Company to conduct the USA and Canada studies simultaneously using the same study design and clinical protocol, so that patient data obtained from both USA and Canada can be shared and used towards obtaining commercial approval for the system from both countries
Source
Medifocus, Inc.
среда, 11 мая 2011 г.
European Breast Cancer Conference, Barcelona, Spain
The 7th European Breast Cancer Conference (EBCC-7) will be held in Barcelona, Spain (Centre Convencions Internacional (CCIB - FORUM), Rambla Prim 1-17, ES-08019) from Wednesday 24 - Saturday 27 March 2010.
The most exciting breast cancer conference in Europe, it is the only one that involves all the major players in breast cancer. The conference encourages interaction and collaboration between clinicians, scientists and patients in a partnership of equals to talk not just about scientific advances, but also the ethical, social, political, and practical issues associated with caring for patients with breast cancer. EBCC-7 is expected to attract over 5000 delegates from around 90 countries worldwide.
The conference covers the entire spectrum of breast cancer and highlights what is new across fields as diverse as:
the impact of lifestyle on breast cancer
is tailored chemotherapy becoming a reality?
breast cancer during and after pregnancy
gene profiling and treatment of disease
the impact of chemotherapy on cognitive function
To find details of the programme: Visit the EBCC-7 web site.
Source: Mary Rice
ECCO-the European CanCer Organisation
The most exciting breast cancer conference in Europe, it is the only one that involves all the major players in breast cancer. The conference encourages interaction and collaboration between clinicians, scientists and patients in a partnership of equals to talk not just about scientific advances, but also the ethical, social, political, and practical issues associated with caring for patients with breast cancer. EBCC-7 is expected to attract over 5000 delegates from around 90 countries worldwide.
The conference covers the entire spectrum of breast cancer and highlights what is new across fields as diverse as:
the impact of lifestyle on breast cancer
is tailored chemotherapy becoming a reality?
breast cancer during and after pregnancy
gene profiling and treatment of disease
the impact of chemotherapy on cognitive function
To find details of the programme: Visit the EBCC-7 web site.
Source: Mary Rice
ECCO-the European CanCer Organisation
вторник, 10 мая 2011 г.
Study Identifies Mechanism Which May Help Tamoxifen Work Better
The "crosstalk" between estrogen and a special protein responsible for cell development (Notch) helps breast cancer cells proliferate and spread, a new study shows.
"Breast cancer cells respond to loss of estrogen, which is caused by commonly used hormonal therapy, by increasing the Notch signal," said senior study investigator Dr. Lucio Miele, professor, departments of pathology, pharmacology and experimental therapeutics, Loyola University Chicago Stritch School of Medicine, Maywood, Ill. "This helps the cancer cells survive the loss of estrogen."
"Blocking the Notch pathway with a Notch inhibitor offers a new strategy to stopping breast cancer," said Miele, director, breast cancer basic science program, Cardinal Bernardin Cancer Center, Loyola University Health System. He presented the findings here today at the 29th annual San Antonio Breast Cancer Symposium.
Notch inhibitors are currently in early human clinical trials.
"Results of our study shows that in estrogen receptor positive cancers, a drug which inhibits the Notch protein should be used in combination with estrogen inhibitors," said Miele. "In estrogen receptor negative cancers, the Notch inhibitor can be used alone or with chemotherapy."
A significant number of people currently become resistant to the breast cancer drug tamoxifen. "For tamoxifen to work better, you need to inhibit the Notch pathway," said co-author Dr. Kathy S. Albain, professor, division of hematology/oncology, department of medicine, Loyola University Chicago Stritch School of Medicine.
"This can be done by using a novel drug to block the Notch pathway while simultaneously controlling estrogen signaling through the estrogen receptor," said Albain, director, thoracic oncology clinical research program; director, breast clinical research program; and co-director, multidisciplinary breast oncology center; Loyola University Health System, Maywood, Ill.
Albain also said this research suggests new therapeutic strategies for women with breast cancer.
Co-authors of the study are principal investigator Paola Rizzo, Ph.D., department of pathology, Loyola University Chicago Stritch School of Medicine, Maywood, Ill.; Jieun Yun, department of biopharmaceutical sciences, University of Illinois at Chicago; Lu Hao, Oncology Institute, Loyola University Health System; Debra Tonetti, Ph.D., biopharmaceutical sciences, University of Illinois at Chicago; Albain; and Miele.
For more information on Loyola University Health System, log onto loyolamedicine
The 29th Annual San Antonio Breast Cancer Symposium meeting at the Henry B. Gonzalez Convention Center, San Antonio, Tex., runs through December 17, 2006.
Loyola University Health System, a wholly owned subsidiary of Loyola University Chicago (LUC), includes the private teaching hospital at Loyola University Medical Center (LUMC), 14 specialty and primary care centers in the western and southwestern suburbs, the Loyola Ambulatory Surgery Center at Oakbrook and the Loyola Oakbrook Terrace Imaging Center; and serves as co-owner-operator of RML Specialty Hospital, a long-term acute hospital specializing in ventilation weaning and other medically complex patients in suburban Hinsdale, Ill. Loyola is nationally recognized for its specialty care and groundbreaking research in cancer, neurological disorders, neonatology and the treatment of heart disease. The 61-acre medical center campus in Maywood, Ill., includes the 523-licensed bed Loyola University Hospital with a Level I trauma center, the region’s largest burn unit, one of the Midwest’s most comprehensive organ transplant programs, the Russo Surgical Pavilion and the Ronald McDonald® Children’s Hospital of LUMC. Also on campus are Loyola’s Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, Loyola Outpatient Center and LUC Stritch School of Medicine. The medical school includes the Cardiovascular Institute, Oncology Institute, Burn & Shock Trauma Institute, Neuroscience Institute and the Neiswanger Institute for Bioethics and Health Policy.
Loyola University Health System
2160 S. First Ave.
Maywood, IL 60153
United States
luhs
"Breast cancer cells respond to loss of estrogen, which is caused by commonly used hormonal therapy, by increasing the Notch signal," said senior study investigator Dr. Lucio Miele, professor, departments of pathology, pharmacology and experimental therapeutics, Loyola University Chicago Stritch School of Medicine, Maywood, Ill. "This helps the cancer cells survive the loss of estrogen."
"Blocking the Notch pathway with a Notch inhibitor offers a new strategy to stopping breast cancer," said Miele, director, breast cancer basic science program, Cardinal Bernardin Cancer Center, Loyola University Health System. He presented the findings here today at the 29th annual San Antonio Breast Cancer Symposium.
Notch inhibitors are currently in early human clinical trials.
"Results of our study shows that in estrogen receptor positive cancers, a drug which inhibits the Notch protein should be used in combination with estrogen inhibitors," said Miele. "In estrogen receptor negative cancers, the Notch inhibitor can be used alone or with chemotherapy."
A significant number of people currently become resistant to the breast cancer drug tamoxifen. "For tamoxifen to work better, you need to inhibit the Notch pathway," said co-author Dr. Kathy S. Albain, professor, division of hematology/oncology, department of medicine, Loyola University Chicago Stritch School of Medicine.
"This can be done by using a novel drug to block the Notch pathway while simultaneously controlling estrogen signaling through the estrogen receptor," said Albain, director, thoracic oncology clinical research program; director, breast clinical research program; and co-director, multidisciplinary breast oncology center; Loyola University Health System, Maywood, Ill.
Albain also said this research suggests new therapeutic strategies for women with breast cancer.
Co-authors of the study are principal investigator Paola Rizzo, Ph.D., department of pathology, Loyola University Chicago Stritch School of Medicine, Maywood, Ill.; Jieun Yun, department of biopharmaceutical sciences, University of Illinois at Chicago; Lu Hao, Oncology Institute, Loyola University Health System; Debra Tonetti, Ph.D., biopharmaceutical sciences, University of Illinois at Chicago; Albain; and Miele.
For more information on Loyola University Health System, log onto loyolamedicine
The 29th Annual San Antonio Breast Cancer Symposium meeting at the Henry B. Gonzalez Convention Center, San Antonio, Tex., runs through December 17, 2006.
Loyola University Health System, a wholly owned subsidiary of Loyola University Chicago (LUC), includes the private teaching hospital at Loyola University Medical Center (LUMC), 14 specialty and primary care centers in the western and southwestern suburbs, the Loyola Ambulatory Surgery Center at Oakbrook and the Loyola Oakbrook Terrace Imaging Center; and serves as co-owner-operator of RML Specialty Hospital, a long-term acute hospital specializing in ventilation weaning and other medically complex patients in suburban Hinsdale, Ill. Loyola is nationally recognized for its specialty care and groundbreaking research in cancer, neurological disorders, neonatology and the treatment of heart disease. The 61-acre medical center campus in Maywood, Ill., includes the 523-licensed bed Loyola University Hospital with a Level I trauma center, the region’s largest burn unit, one of the Midwest’s most comprehensive organ transplant programs, the Russo Surgical Pavilion and the Ronald McDonald® Children’s Hospital of LUMC. Also on campus are Loyola’s Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, Loyola Outpatient Center and LUC Stritch School of Medicine. The medical school includes the Cardiovascular Institute, Oncology Institute, Burn & Shock Trauma Institute, Neuroscience Institute and the Neiswanger Institute for Bioethics and Health Policy.
Loyola University Health System
2160 S. First Ave.
Maywood, IL 60153
United States
luhs
понедельник, 9 мая 2011 г.
BiPar Sciences Announces Update On The Clinical Development Progress Of BSI-201 For Metastatic Triple-Negative Breast Cancer
Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) and its wholly-owned subsidiary, BiPar Sciences, announced that the clinical development program in metastatic triple-negative breast cancer (mTNBC) for the investigational PARP1 inhibitor, BSI-201, progresses as planned with the Phase 3 study meeting expectations on patient accrual and trial site coverage in the United States. Study investigators have enrolled 214 of the target number of 420 patients.
BSI-201 entered a Phase 3 clinical trial in the United States in July 2009 and is being evaluated in
combination with chemotherapy in patients with mTNBC, a condition defined by tumors lacking
expression of estrogen, progesterone receptors and without overexpression of HER2. BSI-201 is a
novel investigational targeted therapy that inhibits poly (ADP-ribose) polymerase (PARP1), an
enzyme involved in DNA damage repair.
The decision to commence with the Phase 3 study in July was based on the encouraging Phase 2
study results presented at ASCO on May 31, 2009. In the Phase 2 clinical trial, women with mTNBC
who were randomly assigned to receive gemcitabine and carboplatin (GC) in combination with the
investigational agent BSI-201 or GC alone. Updated Phase 2 data including overall survival were
presented, Friday, December 11, at 5:30 pm CST, at a poster session at the 32nd Annual San
Antonio Breast Cancer Symposium (SABCS).
The addition of BSI-201 to GC improved median overall survival from 7.7 months to 12.2 months.
(HR=0.5, p=0.005). BSI-201 did not add to the frequency or severity of adverse events associated
with chemotherapy. This is not a final analysis of the Phase 2 data, but rather an updated analysis of
overall survival. Median survival has not yet been reached in the BSI-201 arm, therefore the data
cut-off period for the Phase 2 trial from September to November.
"The updated analysis from the Phase 2 program, including data on overall survival, are consistent
with the positive results presented earlier this year at ASCO," declared Marc Cluzel, Executive Vice
President, R&D, sanofi-aventis. "We are very encouraged by the fast recruitment of patients in
Phase 3 trial. We hope the findings will lead to emerging strategy that may help women with
metastatic triple negative breast cancer."
The U.S. Food and Drug Administration (FDA) granted Fast Track designation to BSI-201 for mTNBC.
As described by the FDA, the Fast Track process is designed to expedite the review of drugs being
developed for serious diseases with the potential to address an unmet medical need.
About the BSI-201 Phase 3 Trial
The Phase 3 trial is a multi-center, randomized trial designed to evaluate the safety and efficacy of
BSI-201 when combined with gemcitabine and carboplatin (GC) in women with mTNBC. A total of
420 mTNBC patients, who have received 0-2 prior therapies in the metastatic setting will be
randomized to receive GC with or without BSI-201.
The co-primary objectives of the Phase 3 study are to assess improvement in progression-free
survival and overall survival. The secondary objectives are to assess objective response rate and
safety. The trial encompasses an estimated 94 sites in the United States. Importantly, this trial will
have a crossover provision that will ensure that all patients enrolled in the BSI-201 Phase 3 clinical
trial have the potential opportunity to receive BSI-201 (patients randomly assigned to the control arm
may receive BSI-201 upon disease progression).
About BSI-201
BSI-201 is a potential first-in-class investigational targeted therapy designed to inhibit poly (ADPribose) polymerase (PARP1), an enzyme involved in DNA damage repair. Among other
investigational PARP inhibitors in the industry, BSI-201 is the farthest along in clinical development in
the mTNBC setting. BSI-201 is currently being evaluated for its potential to enhance the effect of
chemotherapy-induced DNA damage on cancer cells where PARP hyperactivity was demonstrated.
BSI-201 is in Phase 3 for mTNBC, as well as in Phase 2 trials in patients with ovarian, uterine, brain
and lung cancers.
About Triple-Negative Breast Cancer
When patients are diagnosed with breast cancer, their tumors are routinely tested for the presence of
estrogen and progesterone receptors and for the over-expression of HER2. Commonly used breast
cancer therapies target these receptors; for example, tamoxifen for estrogen receptor and
trastuzumab for HER2. However, 15-20 percent of all breast cancers lack over-expression of all three
proteins, thus giving rise to the term "triple-negative breast cancer" or "TNBC."
TNBC can be an aggressive disease, with higher rates of metastases and poorer survival rates than
other breast cancer subtypes. No treatment has been approved specifically for TNBC.
About BiPar Sciences
BiPar Sciences is a biopharmaceutical organization dedicated to pioneering novel tumor-selective
therapies designed to address urgent unmet needs of cancer patients. In addition to BSI-201, the
company also has two additional compounds in preclinical development. BiPar Sciences, located in
South San Francisco, California, is an independent, wholly owned subsidiary of sanofi-aventis, Inc.
About Sanofi Aventis
Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes
therapeutic solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT:
SAN) and in New York (NYSE: SNY).
Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include product development, product potential projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements
regarding future performance. Forward-looking statements are generally identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally
beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMEA, regarding whether and when to
approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such products candidates, the absence of guarantee that the products candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives as well as those discussed or identified in the public filings with
the SEC and the AMF made by sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2008. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.
Source: Sanofi Aventis
BSI-201 entered a Phase 3 clinical trial in the United States in July 2009 and is being evaluated in
combination with chemotherapy in patients with mTNBC, a condition defined by tumors lacking
expression of estrogen, progesterone receptors and without overexpression of HER2. BSI-201 is a
novel investigational targeted therapy that inhibits poly (ADP-ribose) polymerase (PARP1), an
enzyme involved in DNA damage repair.
The decision to commence with the Phase 3 study in July was based on the encouraging Phase 2
study results presented at ASCO on May 31, 2009. In the Phase 2 clinical trial, women with mTNBC
who were randomly assigned to receive gemcitabine and carboplatin (GC) in combination with the
investigational agent BSI-201 or GC alone. Updated Phase 2 data including overall survival were
presented, Friday, December 11, at 5:30 pm CST, at a poster session at the 32nd Annual San
Antonio Breast Cancer Symposium (SABCS).
The addition of BSI-201 to GC improved median overall survival from 7.7 months to 12.2 months.
(HR=0.5, p=0.005). BSI-201 did not add to the frequency or severity of adverse events associated
with chemotherapy. This is not a final analysis of the Phase 2 data, but rather an updated analysis of
overall survival. Median survival has not yet been reached in the BSI-201 arm, therefore the data
cut-off period for the Phase 2 trial from September to November.
"The updated analysis from the Phase 2 program, including data on overall survival, are consistent
with the positive results presented earlier this year at ASCO," declared Marc Cluzel, Executive Vice
President, R&D, sanofi-aventis. "We are very encouraged by the fast recruitment of patients in
Phase 3 trial. We hope the findings will lead to emerging strategy that may help women with
metastatic triple negative breast cancer."
The U.S. Food and Drug Administration (FDA) granted Fast Track designation to BSI-201 for mTNBC.
As described by the FDA, the Fast Track process is designed to expedite the review of drugs being
developed for serious diseases with the potential to address an unmet medical need.
About the BSI-201 Phase 3 Trial
The Phase 3 trial is a multi-center, randomized trial designed to evaluate the safety and efficacy of
BSI-201 when combined with gemcitabine and carboplatin (GC) in women with mTNBC. A total of
420 mTNBC patients, who have received 0-2 prior therapies in the metastatic setting will be
randomized to receive GC with or without BSI-201.
The co-primary objectives of the Phase 3 study are to assess improvement in progression-free
survival and overall survival. The secondary objectives are to assess objective response rate and
safety. The trial encompasses an estimated 94 sites in the United States. Importantly, this trial will
have a crossover provision that will ensure that all patients enrolled in the BSI-201 Phase 3 clinical
trial have the potential opportunity to receive BSI-201 (patients randomly assigned to the control arm
may receive BSI-201 upon disease progression).
About BSI-201
BSI-201 is a potential first-in-class investigational targeted therapy designed to inhibit poly (ADPribose) polymerase (PARP1), an enzyme involved in DNA damage repair. Among other
investigational PARP inhibitors in the industry, BSI-201 is the farthest along in clinical development in
the mTNBC setting. BSI-201 is currently being evaluated for its potential to enhance the effect of
chemotherapy-induced DNA damage on cancer cells where PARP hyperactivity was demonstrated.
BSI-201 is in Phase 3 for mTNBC, as well as in Phase 2 trials in patients with ovarian, uterine, brain
and lung cancers.
About Triple-Negative Breast Cancer
When patients are diagnosed with breast cancer, their tumors are routinely tested for the presence of
estrogen and progesterone receptors and for the over-expression of HER2. Commonly used breast
cancer therapies target these receptors; for example, tamoxifen for estrogen receptor and
trastuzumab for HER2. However, 15-20 percent of all breast cancers lack over-expression of all three
proteins, thus giving rise to the term "triple-negative breast cancer" or "TNBC."
TNBC can be an aggressive disease, with higher rates of metastases and poorer survival rates than
other breast cancer subtypes. No treatment has been approved specifically for TNBC.
About BiPar Sciences
BiPar Sciences is a biopharmaceutical organization dedicated to pioneering novel tumor-selective
therapies designed to address urgent unmet needs of cancer patients. In addition to BSI-201, the
company also has two additional compounds in preclinical development. BiPar Sciences, located in
South San Francisco, California, is an independent, wholly owned subsidiary of sanofi-aventis, Inc.
About Sanofi Aventis
Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes
therapeutic solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT:
SAN) and in New York (NYSE: SNY).
Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include product development, product potential projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements
regarding future performance. Forward-looking statements are generally identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally
beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMEA, regarding whether and when to
approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such products candidates, the absence of guarantee that the products candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives as well as those discussed or identified in the public filings with
the SEC and the AMF made by sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2008. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.
Source: Sanofi Aventis
воскресенье, 8 мая 2011 г.
HOXB7 Gene Promotes Tamoxifen Resistance
Many postmenopausal women with early-stage breast cancers who initially respond well to tamoxifen become resistant to the drug over time and develop recurrent tumors. Johns Hopkins Kimmel Cancer Center researchers have found that a gene called HOXB7 may be the culprit in tamoxifen resistance.
Taken by mouth, tamoxifen is used at every stage of breast cancer to treat existing tumors and prevent new ones from developing. The drug works only in women whose tumor cells have a protein, called the estrogen receptor, which binds to the estrogen hormone. Tamoxifen binds to this estrogen receptor and blocks estrogen's effect on fueling cancer cells.
In experiments on cancer cells, the scientists found that when the HOXB7 gene is overexpressed, as occurs in many breast cancers, tumors cells became resistant to tamoxifen. Overexpression of HOXB7 results in proteins that interact with a series of other estrogen-activated genes and proteins, including the HER2 gene, known to make breast cancers aggressive. When the scientists knocked out the HOXB7 gene in one group of breast cancer cells, HER2 activation decreased and the cells became more responsive to tamoxifen. The scientists then showed how the HOXB7-HER2 interaction works.
"HOXB7 appears crucial in orchestrating estrogen receptors, HER2 and other receptors that promote aggressive tumor growth in breast cancer cells," says senior author Saraswati Sukumar, PhD, professor of oncology and co-director of the Breast Cancer Program at Johns Hopkins. "Dialing down expression of the HOXB7 gene could stave off tamoxifen resistance."
Though it's not yet evident how to shut down HOXB7, Sukumar says that oncologists could potentially use the drug Herceptin to kill tumors in patients whose HER2 expression increases.
(Presentation # PD05-10 presented by Johns Hopkins Kimmel Cancer Center scientists during the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium.)
Source:
Vanessa Wasta
Johns Hopkins Medical Institutions
View drug information on Herceptin.
Taken by mouth, tamoxifen is used at every stage of breast cancer to treat existing tumors and prevent new ones from developing. The drug works only in women whose tumor cells have a protein, called the estrogen receptor, which binds to the estrogen hormone. Tamoxifen binds to this estrogen receptor and blocks estrogen's effect on fueling cancer cells.
In experiments on cancer cells, the scientists found that when the HOXB7 gene is overexpressed, as occurs in many breast cancers, tumors cells became resistant to tamoxifen. Overexpression of HOXB7 results in proteins that interact with a series of other estrogen-activated genes and proteins, including the HER2 gene, known to make breast cancers aggressive. When the scientists knocked out the HOXB7 gene in one group of breast cancer cells, HER2 activation decreased and the cells became more responsive to tamoxifen. The scientists then showed how the HOXB7-HER2 interaction works.
"HOXB7 appears crucial in orchestrating estrogen receptors, HER2 and other receptors that promote aggressive tumor growth in breast cancer cells," says senior author Saraswati Sukumar, PhD, professor of oncology and co-director of the Breast Cancer Program at Johns Hopkins. "Dialing down expression of the HOXB7 gene could stave off tamoxifen resistance."
Though it's not yet evident how to shut down HOXB7, Sukumar says that oncologists could potentially use the drug Herceptin to kill tumors in patients whose HER2 expression increases.
(Presentation # PD05-10 presented by Johns Hopkins Kimmel Cancer Center scientists during the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium.)
Source:
Vanessa Wasta
Johns Hopkins Medical Institutions
View drug information on Herceptin.
суббота, 7 мая 2011 г.
Largest single-institution study demonstrates Mammosite is a safe breast cancer treatment
Treating breast cancer with MammoSite® resulted in a low risk of complications and was generally well tolerated, according to a University of Pittsburgh School of Medicine study presented today at the 47th annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO) in Denver.
MammoSite, a type of breast brachytherapy (bray-kee-therapy), uses a single catheter inserted into the breast following lumpectomy, or surgical removal of a tumor, to deliver a high dose of radiation. Once the catheter is inserted, a tiny balloon is inflated and loaded with radioactive seeds that deliver prescribed levels of radiation to targeted tissue surrounding the tumor site.
"MammoSite is a type of partial breast irradiation that delivers radiation from the inside of the breast directly to the tumor site where cancer cells are most likely to reside," said Sushil Beriwal, M.D., assistant professor at the University of Pittsburgh School of Medicine and medical director of radiation oncology at Magee-Womens Hospital of the University of Pittsburgh Medical Center (UPMC). "Ours is one of the largest single-institution studies to confirm that it does this safely and with an acceptable level of toxicity."
The study, which was designed to evaluate early outcomes of MammoSite brachytherapy, and was approved by the FDA in 2002, evaluated toxicity in 100 patients treated between June 2002 and October 2004 at the University of Pittsburgh Cancer Institute. The patients were followed between three and 30 months subsequent to treatment with an average follow-up time of one year. After treatment, patients were assessed at one week, one month and at three-month intervals. While 14 percent of women had to have the catheter removed because of various reasons, the majority of the patients (86 percent) underwent treatment.
Post-treatment complications included balloon rupture, infections, skin toxicity and seromas (persistence of the cavity where the lump was removed). Study results indicated that balloon rupture occurred in six patients (7 percent) and wound infections occurred in 10 patients (12 percent). No patients had serious skin toxicities from treatment. A palpable seroma was observed in 34 of the patients (40 percent) and persisted beyond six months of treatment in 22 patients (26 percent).
The study also evaluated cosmetic outcome of MammoSite treatment. Cosmetic outcome refers to the physical similarity between the treated breast and the untreated breast. Forty-eight patients (56 percent) had excellent cosmetic outcomes; 32 patients (37 percent) had good cosmetic outcomes; and seven patients (7 percent) had fair cosmetic outcomes.
"Our findings demonstrate that the toxicities associated with MammoSite were similar to results reported in the MammoSite brachytherapy registry trial," said Dr. Beriwal. "The complications were acceptable and the cosmetic outcome was comparable to what we might see with standard external beam radiation." Dr. Beriwal added that follow-up studies will seek to assess the long-term effects as well as the efficacy of the treatment compared with standard external beam radiation therapy and other types of breast brachytherapy.
MammoSite is manufactured by Cytyc Corporation based in Alpharetta, Ga.
Also involved in the study from the University of Pittsburgh's department of radiation oncology were Anurag Agarwal, M.D.; Dwight E. Heron, M.D.; Jeffrey Falk, M.D., Ronald Johnson, M.D.; Robert Mogus, R.T.T.; Hayeon Kim, M.S.; Kristina Gerszten, M.D.; and Melvin Deutsch, M.D.
Clare Collins / Michele Baum
CollCXupmc / BaumMDupmc
University of Pittsburgh Medical Center
upmc
MammoSite, a type of breast brachytherapy (bray-kee-therapy), uses a single catheter inserted into the breast following lumpectomy, or surgical removal of a tumor, to deliver a high dose of radiation. Once the catheter is inserted, a tiny balloon is inflated and loaded with radioactive seeds that deliver prescribed levels of radiation to targeted tissue surrounding the tumor site.
"MammoSite is a type of partial breast irradiation that delivers radiation from the inside of the breast directly to the tumor site where cancer cells are most likely to reside," said Sushil Beriwal, M.D., assistant professor at the University of Pittsburgh School of Medicine and medical director of radiation oncology at Magee-Womens Hospital of the University of Pittsburgh Medical Center (UPMC). "Ours is one of the largest single-institution studies to confirm that it does this safely and with an acceptable level of toxicity."
The study, which was designed to evaluate early outcomes of MammoSite brachytherapy, and was approved by the FDA in 2002, evaluated toxicity in 100 patients treated between June 2002 and October 2004 at the University of Pittsburgh Cancer Institute. The patients were followed between three and 30 months subsequent to treatment with an average follow-up time of one year. After treatment, patients were assessed at one week, one month and at three-month intervals. While 14 percent of women had to have the catheter removed because of various reasons, the majority of the patients (86 percent) underwent treatment.
Post-treatment complications included balloon rupture, infections, skin toxicity and seromas (persistence of the cavity where the lump was removed). Study results indicated that balloon rupture occurred in six patients (7 percent) and wound infections occurred in 10 patients (12 percent). No patients had serious skin toxicities from treatment. A palpable seroma was observed in 34 of the patients (40 percent) and persisted beyond six months of treatment in 22 patients (26 percent).
The study also evaluated cosmetic outcome of MammoSite treatment. Cosmetic outcome refers to the physical similarity between the treated breast and the untreated breast. Forty-eight patients (56 percent) had excellent cosmetic outcomes; 32 patients (37 percent) had good cosmetic outcomes; and seven patients (7 percent) had fair cosmetic outcomes.
"Our findings demonstrate that the toxicities associated with MammoSite were similar to results reported in the MammoSite brachytherapy registry trial," said Dr. Beriwal. "The complications were acceptable and the cosmetic outcome was comparable to what we might see with standard external beam radiation." Dr. Beriwal added that follow-up studies will seek to assess the long-term effects as well as the efficacy of the treatment compared with standard external beam radiation therapy and other types of breast brachytherapy.
MammoSite is manufactured by Cytyc Corporation based in Alpharetta, Ga.
Also involved in the study from the University of Pittsburgh's department of radiation oncology were Anurag Agarwal, M.D.; Dwight E. Heron, M.D.; Jeffrey Falk, M.D., Ronald Johnson, M.D.; Robert Mogus, R.T.T.; Hayeon Kim, M.S.; Kristina Gerszten, M.D.; and Melvin Deutsch, M.D.
Clare Collins / Michele Baum
CollCXupmc / BaumMDupmc
University of Pittsburgh Medical Center
upmc
пятница, 6 мая 2011 г.
Advocates Urge Restoring Funding To $150M For Defense Department Breast Cancer Research Program
Advocates at a National Breast Cancer Coalition forum on Monday said that annual funding should be increased to $150 million for a Department of Defense program that involves researchers and patient advocates in breast cancer research spending decisions, CQ HealthBeat reports. The program, which was launched in 1992, received $150 million annually from fiscal year 2002 to FY 2005, and it received $127.5 million in both FY 2006 and FY 2007, according to the National Breast Cancer Coalition. A letter being circulated by Reps. Judy Biggert (R-Ill.), Tom Davis (R-Va.), Nita Lowey (D-N.Y.) and James McGovern (D-Mass.) says that the program has led to new methods of extracting breast cancer cells at early stages, the development of the breast cancer drug Herceptin, and research on the interaction of genetic and environmental factors in causing the disease. The letter, which is being given to appropriators, says that "we do not yet know how to prevent the disease" and that there is not a cure or an "accurate, reliable early detection method" (CQ HealthBeat, 3/5).
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
четверг, 5 мая 2011 г.
Breast cancer risk increased for African-Americans with mitochondrial DNA variant
African-American women who carry the 10398A mitochondrial DNA allele are 60 percent more likely to develop invasive breast cancer than African-American females without that genetic marker, according to research published in the September 1 issue of "Cancer Research."
"These findings support the notion that variations in the genetic sequence of mitochondrial DNA are underappreciated factors in breast carcinogenesis," said Jeffrey Canter, M.D., M.P.H., of the Center for Human Genetics Research at Vanderbilt University, Nashville, Tenn.
The mitochondria, located outside the nucleus, are the cell's energy-producing factories. Unlike chromosomal DNA, the mitochondrial DNA is passed to offspring exclusively from the mother and carries important information necessary for the production of adenosine triphosphate, ATP, the energy source for cellular function.
In this study, the researchers focused on a specific variation (G10398A) in a mitochondrial gene called ND3, which serves as the blueprint for an important component of an enzyme called NADH dehydrogenase. In its changed state, however, an adenine is substituted for a guanine in the DNA structure, resulting in the enzyme containing the amino acid threonine instead of an alanine.
The clinical implication of this seemingly trivial alteration is profound. Among the greater population of humans, carriers of 10398A appear to be at higher risk for Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), and other neurological disorders.
Canter and colleagues determined that the errant allele is associated with a significantly higher risk for breast cancer among African-American women who carry 10398A, but has no apparent implications for breast cancer in white women. A much greater proportion of the white female population, 80 percent, already carries the 10398A version of the NADH dehydrogenase gene than the five percent of black American women with the allele.
In a pilot study conducted by Canter and his colleagues at Vanderbilt University, the mitochondrial allele appeared to be associated with a three-fold increase in the risk of African-American women developing invasive breast cancer. The evidence in the initial Vanderbilt study compelled Canter and his colleagues to investigate the ramifications of 10398A among a much larger group of women.
"Through our collaboration with Dr. Robert Millikan, at the University of North Carolina, we validated the Vanderbilt finding with a larger number of women who participated in the Carolina Breast Cancer Study," Canter said. "We looked at 1259 women including 654 breast cancer patients. African-American women with the 10398A allele in this larger study had a significantly increased risk for invasive breast cancer."
The change in cellular function due to the single amino acid substitution encoded by 10398A remains to be defined, Canter said.
"The hundreds and hundreds of African-American women participating in the Carolina Breast Cancer Study made this discovery possible. Their willingness to take part in this outstanding population-based study and contribute DNA for genetic analysis is a remarkable legacy," stated Canter.
"We suspect that the mitochondrial 10398A allele impairs the function of the mitochondrial electron chain, resulting in increased oxidative stress and breast cancer susceptibility," Canter said.
Canter's colleagues included Vanderbilt University researchers Asha Kallianpur, M.D., M.P.H, and Fritz Parl, M.D., Ph.D.; and Robert Millikan, D.V.M., Ph.D., University of North Carolina, at Chapel Hill.
Founded in 1907, the American Association for Cancer Research is a professional society of more than 24,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: "Cancer Research"; "Clinical Cancer Research"; "Molecular Cancer Therapeutics"; "Molecular Cancer Research"; and "Cancer Epidemiology, Biomarkers & Prevention." AACR's Annual Meetings attract nearly 16,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.
Russell Vanderboom, Ph.D.
vanderboomaacr
215-440-9300
American Association for Cancer Research
aacr
"These findings support the notion that variations in the genetic sequence of mitochondrial DNA are underappreciated factors in breast carcinogenesis," said Jeffrey Canter, M.D., M.P.H., of the Center for Human Genetics Research at Vanderbilt University, Nashville, Tenn.
The mitochondria, located outside the nucleus, are the cell's energy-producing factories. Unlike chromosomal DNA, the mitochondrial DNA is passed to offspring exclusively from the mother and carries important information necessary for the production of adenosine triphosphate, ATP, the energy source for cellular function.
In this study, the researchers focused on a specific variation (G10398A) in a mitochondrial gene called ND3, which serves as the blueprint for an important component of an enzyme called NADH dehydrogenase. In its changed state, however, an adenine is substituted for a guanine in the DNA structure, resulting in the enzyme containing the amino acid threonine instead of an alanine.
The clinical implication of this seemingly trivial alteration is profound. Among the greater population of humans, carriers of 10398A appear to be at higher risk for Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), and other neurological disorders.
Canter and colleagues determined that the errant allele is associated with a significantly higher risk for breast cancer among African-American women who carry 10398A, but has no apparent implications for breast cancer in white women. A much greater proportion of the white female population, 80 percent, already carries the 10398A version of the NADH dehydrogenase gene than the five percent of black American women with the allele.
In a pilot study conducted by Canter and his colleagues at Vanderbilt University, the mitochondrial allele appeared to be associated with a three-fold increase in the risk of African-American women developing invasive breast cancer. The evidence in the initial Vanderbilt study compelled Canter and his colleagues to investigate the ramifications of 10398A among a much larger group of women.
"Through our collaboration with Dr. Robert Millikan, at the University of North Carolina, we validated the Vanderbilt finding with a larger number of women who participated in the Carolina Breast Cancer Study," Canter said. "We looked at 1259 women including 654 breast cancer patients. African-American women with the 10398A allele in this larger study had a significantly increased risk for invasive breast cancer."
The change in cellular function due to the single amino acid substitution encoded by 10398A remains to be defined, Canter said.
"The hundreds and hundreds of African-American women participating in the Carolina Breast Cancer Study made this discovery possible. Their willingness to take part in this outstanding population-based study and contribute DNA for genetic analysis is a remarkable legacy," stated Canter.
"We suspect that the mitochondrial 10398A allele impairs the function of the mitochondrial electron chain, resulting in increased oxidative stress and breast cancer susceptibility," Canter said.
Canter's colleagues included Vanderbilt University researchers Asha Kallianpur, M.D., M.P.H, and Fritz Parl, M.D., Ph.D.; and Robert Millikan, D.V.M., Ph.D., University of North Carolina, at Chapel Hill.
Founded in 1907, the American Association for Cancer Research is a professional society of more than 24,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: "Cancer Research"; "Clinical Cancer Research"; "Molecular Cancer Therapeutics"; "Molecular Cancer Research"; and "Cancer Epidemiology, Biomarkers & Prevention." AACR's Annual Meetings attract nearly 16,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.
Russell Vanderboom, Ph.D.
vanderboomaacr
215-440-9300
American Association for Cancer Research
aacr
среда, 4 мая 2011 г.
Newly Announced Rules Expand Access To Mammography And Other Early Detection Services At No Cost To Patients
Susan G. Komen for the Cure® and the Susan G. Komen for the Cure® Advocacy Alliance applauded new federal rules that will expand access to potentially life-saving care for millions of Americans.
"Today's announcement is a critical step in ensuring the promise of health reform is delivered to all women," said Ambassador Nancy G. Brinker, founder and CEO of Susan G. Komen for the Cure. "This new rule means money will no longer be an obstacle for women who want or need a mammogram. Ultimately, this will save lives."
The new interim regulations were issued today by the Department of Health and Human Services (HHS) as part of its implementation of the new health reform law (the Patient Protection and Affordable Care Act). The regulations will require private health insurers to cover preventive and early detection services, including annual screening mammography for women age 40 and older, with no cost sharing or co-pays in health plans issued after September 23, 2010. The rules will also apply to all plans offered through state-based health insurance exchanges when they become operational in 2014. Plans established prior to September 23, 2010 are not subject to the new regulations.
Extending this protection to women age 40 and older was particularly welcomed by the Komen Advocacy Alliance. "By requiring health insurers to offer no-cost access to mammography for women age 40 to 49, HHS has relieved concerns women have had since the United States Preventive Services Task Force issued its controversial guidelines last fall," said Jennifer M. Luray, President of the Komen Advocacy Alliance. "We are grateful to Senators Barbara Mikulski (R-MD) and David Vitter (R-LA) for their roles in ensuring all women 40 and above have this access, in accordance with Komen's long-held recommendations."
Komen notes that early detection is a key to surviving breast cancer. While more than 200,000 women are expected to be diagnosed with breast cancer this year, and almost 40,000 will die, 98 percent of breast cancer patients will survive at least five years if the cancer is discovered before it has spread beyond the breast compared to only 23 percent when the cancer has spread to other parts of the body.
While applauding today's announcement, the Komen Advocacy Alliance also cautioned that government must maintain the safety net screening services funded by the Centers for Disease Control and Prevention, states and non-profits until all women have access to these new cancer screening benefits and we are assured women know how and when to access them.
Source:
Susan G. Komen for the Cure
Susan G. Komen for the Cure® Advocacy Alliance
"Today's announcement is a critical step in ensuring the promise of health reform is delivered to all women," said Ambassador Nancy G. Brinker, founder and CEO of Susan G. Komen for the Cure. "This new rule means money will no longer be an obstacle for women who want or need a mammogram. Ultimately, this will save lives."
The new interim regulations were issued today by the Department of Health and Human Services (HHS) as part of its implementation of the new health reform law (the Patient Protection and Affordable Care Act). The regulations will require private health insurers to cover preventive and early detection services, including annual screening mammography for women age 40 and older, with no cost sharing or co-pays in health plans issued after September 23, 2010. The rules will also apply to all plans offered through state-based health insurance exchanges when they become operational in 2014. Plans established prior to September 23, 2010 are not subject to the new regulations.
Extending this protection to women age 40 and older was particularly welcomed by the Komen Advocacy Alliance. "By requiring health insurers to offer no-cost access to mammography for women age 40 to 49, HHS has relieved concerns women have had since the United States Preventive Services Task Force issued its controversial guidelines last fall," said Jennifer M. Luray, President of the Komen Advocacy Alliance. "We are grateful to Senators Barbara Mikulski (R-MD) and David Vitter (R-LA) for their roles in ensuring all women 40 and above have this access, in accordance with Komen's long-held recommendations."
Komen notes that early detection is a key to surviving breast cancer. While more than 200,000 women are expected to be diagnosed with breast cancer this year, and almost 40,000 will die, 98 percent of breast cancer patients will survive at least five years if the cancer is discovered before it has spread beyond the breast compared to only 23 percent when the cancer has spread to other parts of the body.
While applauding today's announcement, the Komen Advocacy Alliance also cautioned that government must maintain the safety net screening services funded by the Centers for Disease Control and Prevention, states and non-profits until all women have access to these new cancer screening benefits and we are assured women know how and when to access them.
Source:
Susan G. Komen for the Cure
Susan G. Komen for the Cure® Advocacy Alliance
вторник, 3 мая 2011 г.
In Young Women With Benign Breast Disease, Breast Cancer Risk Varies According To Mayo Clinic Researchers
A type of benign breast disease (BBD) known as atypical hyperplasia substantially increases a young woman's risk of developing breast cancer, even if there is no history of breast cancer in her family, say researchers at Mayo Clinic.
The investigators, who presented their findings at the Cancer Therapy & Research Center-American Association for Cancer Research (CTRC-AACR) San Antonio Breast Cancer Symposium, say the women they studied with this kind of benign breast disease had a relative risk of developing breast cancer that was almost six times greater than women with no evidence of the disease.
Young women diagnosed with two other forms of benign breast disease were at much less risk than patients with atypical hyperplasia, the researchers say. Those with non-proliferative disease were only slightly at increased risk (1.2 times, or .2 percent higher than normal) and women with proliferative disease without atypia had a risk that was doubled. A family history of breast cancer increased risk in these two groups of patients, but only slightly, the researchers say.
"Breast cancer is the leading cause of cancer death in women age 25 to 49, and these young patients also have worse overall survival and increased risk of cancer coming back compared to older women, so it is important that we try to understand how the cancer develops and the measures that help prevent it," says the study's lead investigator, Karthik Ghosh, M.D.
The average age of benign breast disease diagnosis in the 4,460 women included in this study was 39 years old. Within that group, 326 women eventually - sometimes decades later - developed breast cancer.
The study is the latest set of findings in Mayo Clinic's effort to precisely define a woman's risk for developing breast cancer in order to tailor screening and risk-reduction measures to the individual. With support from a $5.8 million Department of Defense Congressionally Directed Medical Research Program, Mayo researchers have been studying benign breast disease in 9,376 women whose lesions were biopsied at Mayo Clinic between 1967 and 1991. The scientists continue to follow the progress of these women.
Their research has led to a number of findings, published in such journals as The New England Journal of Medicine, that are helping researchers predict which benign lesions will become cancerous. For example, they have found that in the entire benign breast disease cohort, women with atypical hyperplasia were more than three times more likely to develop breast cancer. They also found that risk decreases in women diagnosed with benign breast disease when the milk-producing lobular ductal glands - where cancer usually develops - shut down, a process known as lobular regression or involution.
In atyical hyperplasia, an increased number of cells line the milk duct or lobule, than is typical and the cells do not look normal under a microscope, but they are not cancerous, according to Dr. Ghosh. In proliferative disease without atypia, an increased number of cells line the milk duct but they look normal. Women with non-proliferative disease have fibrocystic changes but no increase in cell number.
This study was designed to look specifically at younger women in the group, because the earlier findings suggested these women were at increased risk of developing breast cancer, especially if they were diagnosed with atypical hyperplasia. Among the group of 4,460 women less than 50 years old in the study, 2 percent had been diagnosed with atypical hyperplasia, 72 percent had non-proliferative disease and 26 percent had been diagnosed with proliferative disease without atypia.
Researchers found that after a median follow-up of 20 years, 326 of the women included in this study developed breast cancer. That meant the relative risk of developing the cancer was 1.5 times greater than women not diagnosed with BBD.
They further found that a strong family history of breast cancer was associated with a 2.2 times greater relative risk of cancer development in women with non-proliferative disease or proliferative disease without atypia.
They also found that the 5 percent of women who had complete lobular involution had a reduced relative risk (.68 times less) for developing breast cancer. "The impact of lobular involution on risk, even in young women with benign breast disease, is an interesting finding," Dr. Ghosh says. "It suggests that future research could potentially think about ways of promoting lobular involution as a means to reduce breast cancer risk."
The 2008 San Antonio Breast Cancer Symposium (SABCS) is the first Symposium presented by the CTRC, AACR, and the Baylor College of Medicine. The driving force behind the new collaboration is the shared mission of the organizations to advance progress against breast cancer. By combining their respective strengths, the 2008 San Antonio Breast Cancer Symposium will encompass the full spectrum of breast cancer research and facilitate the rapid transition of new knowledge into improved care for breast cancer patients.
Source: Karl Oestreich
Mayo Clinic
The investigators, who presented their findings at the Cancer Therapy & Research Center-American Association for Cancer Research (CTRC-AACR) San Antonio Breast Cancer Symposium, say the women they studied with this kind of benign breast disease had a relative risk of developing breast cancer that was almost six times greater than women with no evidence of the disease.
Young women diagnosed with two other forms of benign breast disease were at much less risk than patients with atypical hyperplasia, the researchers say. Those with non-proliferative disease were only slightly at increased risk (1.2 times, or .2 percent higher than normal) and women with proliferative disease without atypia had a risk that was doubled. A family history of breast cancer increased risk in these two groups of patients, but only slightly, the researchers say.
"Breast cancer is the leading cause of cancer death in women age 25 to 49, and these young patients also have worse overall survival and increased risk of cancer coming back compared to older women, so it is important that we try to understand how the cancer develops and the measures that help prevent it," says the study's lead investigator, Karthik Ghosh, M.D.
The average age of benign breast disease diagnosis in the 4,460 women included in this study was 39 years old. Within that group, 326 women eventually - sometimes decades later - developed breast cancer.
The study is the latest set of findings in Mayo Clinic's effort to precisely define a woman's risk for developing breast cancer in order to tailor screening and risk-reduction measures to the individual. With support from a $5.8 million Department of Defense Congressionally Directed Medical Research Program, Mayo researchers have been studying benign breast disease in 9,376 women whose lesions were biopsied at Mayo Clinic between 1967 and 1991. The scientists continue to follow the progress of these women.
Their research has led to a number of findings, published in such journals as The New England Journal of Medicine, that are helping researchers predict which benign lesions will become cancerous. For example, they have found that in the entire benign breast disease cohort, women with atypical hyperplasia were more than three times more likely to develop breast cancer. They also found that risk decreases in women diagnosed with benign breast disease when the milk-producing lobular ductal glands - where cancer usually develops - shut down, a process known as lobular regression or involution.
In atyical hyperplasia, an increased number of cells line the milk duct or lobule, than is typical and the cells do not look normal under a microscope, but they are not cancerous, according to Dr. Ghosh. In proliferative disease without atypia, an increased number of cells line the milk duct but they look normal. Women with non-proliferative disease have fibrocystic changes but no increase in cell number.
This study was designed to look specifically at younger women in the group, because the earlier findings suggested these women were at increased risk of developing breast cancer, especially if they were diagnosed with atypical hyperplasia. Among the group of 4,460 women less than 50 years old in the study, 2 percent had been diagnosed with atypical hyperplasia, 72 percent had non-proliferative disease and 26 percent had been diagnosed with proliferative disease without atypia.
Researchers found that after a median follow-up of 20 years, 326 of the women included in this study developed breast cancer. That meant the relative risk of developing the cancer was 1.5 times greater than women not diagnosed with BBD.
They further found that a strong family history of breast cancer was associated with a 2.2 times greater relative risk of cancer development in women with non-proliferative disease or proliferative disease without atypia.
They also found that the 5 percent of women who had complete lobular involution had a reduced relative risk (.68 times less) for developing breast cancer. "The impact of lobular involution on risk, even in young women with benign breast disease, is an interesting finding," Dr. Ghosh says. "It suggests that future research could potentially think about ways of promoting lobular involution as a means to reduce breast cancer risk."
The 2008 San Antonio Breast Cancer Symposium (SABCS) is the first Symposium presented by the CTRC, AACR, and the Baylor College of Medicine. The driving force behind the new collaboration is the shared mission of the organizations to advance progress against breast cancer. By combining their respective strengths, the 2008 San Antonio Breast Cancer Symposium will encompass the full spectrum of breast cancer research and facilitate the rapid transition of new knowledge into improved care for breast cancer patients.
Source: Karl Oestreich
Mayo Clinic
понедельник, 2 мая 2011 г.
Breast Inflammation Is Key To Cancer Growth
It took 12 years and a creation of a highly sophisticated transgenic mouse, but researchers at Kimmel Cancer Center at Jefferson have finally proven a long suspected theory: Inflammation in the breast is key to the development and progression of breast cancer.
In the December 15 issue of Cancer Research, the scientists say they can now definitively show that an inflammatory process within the breast itself promotes growth of breast cancer stem cells responsible for tumor development.
They also demonstrate that inactivating this inflammation selectively within the breast reduced activity of these stem cells, and stopped breast cancer from forming.
"These studies show for the first time that inactivating the NFKB inflammatory pathway in the breast epithelium blocks the onset and progression of breast cancer in living animals," says Richard G. Pestell, M.D., Ph.D., Director, Kimmel Cancer Center and Chairman of Cancer Biology.
"This finding has clinical implications," says co-author Michael Lisanti, Leader of the Program in Molecular Biology and Genetics of Cancer at Jefferson. "Suppressing the whole body's inflammatory process has side effects. These studies provide the rationale for more selective anti-inflammatory therapy directed just to the breast."
Dr. Pestell and his colleagues show the "canonical" NFKB pathway promotes breast cancer development: the first "insult" is provided by the HER2 oncogene, which then activates NFKB (nuclear factor kappa-light-chain-enhancer of activated B cells). NFKB turns on inflammation via tumor-associated macrophages (TAM), which produce tumor growth promoting factors.
Although inflammation, mediated by NFKB, has long been thought to be important in breast cancer development, the theory had been untestable because NF-ОєB is essential to embryonic development, Dr. Pestell says. "When you try to knock out NFKB genes in mice, they die."
He addressed this problem by creating a mouse in which the inflammatory system within the adult animal's normal breast could be regulated. This allows selective inactivation of NFKB in different cell types and took 12 years to accomplish, Dr. Pestell says. "These mice have five co-integrated transgenes."
The mice are programmed to develop breast cancer, but the researchers found that if they selectively blocked inflammation just in the breast, tumors would not develop. "This is a very novel finding," Dr. Pestell says.
They then demonstrated that this inactivation also reduced the number of cancer stem cells in the breast. "That told us that inflammation, through the action of NF-ОєB, is important to the growth and activity of cancer stem cells," Dr. Pestell says. "The transgenic mice are a new technology that can be used by the scientists and the pharmaceutical industry to understand the role of NFKB in different diseases including heart disease, neurodegeneration and other cancers."
The study was funded by support from the National Institutes of Health, the Dr. Ralph and Marian C. Falk Medical Research Trust, and a grant from the Pennsylvania Department of Health.
Researchers from the Nigata University of Pharmacy and Applied Life Sciences in Japan, the National Cancer Institute, the University of Western Australia, and the Lombardi Comprehensive Cancer Center at Georgetown University Medical School contributed to the study.
The authors declare no conflicts of interest.
Source:
Thomas Jefferson University
In the December 15 issue of Cancer Research, the scientists say they can now definitively show that an inflammatory process within the breast itself promotes growth of breast cancer stem cells responsible for tumor development.
They also demonstrate that inactivating this inflammation selectively within the breast reduced activity of these stem cells, and stopped breast cancer from forming.
"These studies show for the first time that inactivating the NFKB inflammatory pathway in the breast epithelium blocks the onset and progression of breast cancer in living animals," says Richard G. Pestell, M.D., Ph.D., Director, Kimmel Cancer Center and Chairman of Cancer Biology.
"This finding has clinical implications," says co-author Michael Lisanti, Leader of the Program in Molecular Biology and Genetics of Cancer at Jefferson. "Suppressing the whole body's inflammatory process has side effects. These studies provide the rationale for more selective anti-inflammatory therapy directed just to the breast."
Dr. Pestell and his colleagues show the "canonical" NFKB pathway promotes breast cancer development: the first "insult" is provided by the HER2 oncogene, which then activates NFKB (nuclear factor kappa-light-chain-enhancer of activated B cells). NFKB turns on inflammation via tumor-associated macrophages (TAM), which produce tumor growth promoting factors.
Although inflammation, mediated by NFKB, has long been thought to be important in breast cancer development, the theory had been untestable because NF-ОєB is essential to embryonic development, Dr. Pestell says. "When you try to knock out NFKB genes in mice, they die."
He addressed this problem by creating a mouse in which the inflammatory system within the adult animal's normal breast could be regulated. This allows selective inactivation of NFKB in different cell types and took 12 years to accomplish, Dr. Pestell says. "These mice have five co-integrated transgenes."
The mice are programmed to develop breast cancer, but the researchers found that if they selectively blocked inflammation just in the breast, tumors would not develop. "This is a very novel finding," Dr. Pestell says.
They then demonstrated that this inactivation also reduced the number of cancer stem cells in the breast. "That told us that inflammation, through the action of NF-ОєB, is important to the growth and activity of cancer stem cells," Dr. Pestell says. "The transgenic mice are a new technology that can be used by the scientists and the pharmaceutical industry to understand the role of NFKB in different diseases including heart disease, neurodegeneration and other cancers."
The study was funded by support from the National Institutes of Health, the Dr. Ralph and Marian C. Falk Medical Research Trust, and a grant from the Pennsylvania Department of Health.
Researchers from the Nigata University of Pharmacy and Applied Life Sciences in Japan, the National Cancer Institute, the University of Western Australia, and the Lombardi Comprehensive Cancer Center at Georgetown University Medical School contributed to the study.
The authors declare no conflicts of interest.
Source:
Thomas Jefferson University
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