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
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