In recent years, a series of highly publicized reports have warned of increases in breast cancer and other health problems in postmenopausal women who take hormone replacement therapy (HRT). But a closer look at the data suggests that those reports were often "distorted, oversimplified, or wrong," according to a paper in the March/April issue of The Cancer Journal: The Journal of Principles & Practice of Oncology. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals, and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry.
Despite "weak or statistically insignificant" data, scientific and media reports have emphasized the dangers of HRT, while downplaying its beneficial effects especially on menopausal symptoms, according to the article by Avrum Z. Bluming, M.D., and Carol Tavris, Ph.D. "Physicians and the public must be cautious about accepting 'findings by press release' in determining whether or not to prescribe or take HRT," according to Drs. Bluming and Tavris. Dr. Bluming is a Board-Certified Medical Oncologist, a Master of the American College of Physicians and a Clinical Professor of Medicine at the University of Southern California. Dr. Tavris is a social psychologist and writer.
Discrepancies Between Reports of HRT Dangers and Supporting Data
Doctors Bluming and Tavris cite the Harvard Nurses' Health Study, published in 1995, which employed retrospective substratification to exaggerate the association between HRT and breast cancer development. Statisticians have cautioned that spurious associations can result from this practice also called "data mining" in which researchers sift through their databases, looking for factors that might affect health outcomes. "The problem is that in a data set of many thousands of people, some relationship that is unearthed retrospectively will turn out to be statistically significant...just by chance."
The authors also criticize the Women's Health Initiative (WHI), published initially in 2002, which reported "relative risk" rather than "absolute risk" associations. This format can make "statistically modest or borderline results...look more impressive than they actually are." The authors note that the 26 percent relative risk of breast cancer in the initial WHI is similar to that reported for unlikely risk factors like eating grapefruit, working on a nightshift, or working as a flight attendant.
The core issue, according to Drs. Bluming and Tavris, is the difference between information and knowledge. "What we're trying to do is make a plea for knowledge, not just information, especially loosely based associations that are generated by epidemiologic studies. That isn't science. Post-hoc findings that make little or no scientific sense may give us clues for future investigation, but they shouldn't be accepted as proof of cause and effect."
Jumble of 'Positive, Negative and Meaningless' Findings
Press releases linking HRT to breast cancer failed to report that the initial WHI report of a 26 percent relative risk did not reach the level of statistical significance. Nevertheless, several editorials by prominent authorities highlighted the increase in risk as "statistically significant" a false claim repeated in news stories.
Subsequent analyses gave varying results: smaller but significant risk, larger but nonsignificant risk, or no significant difference in risk. "It is difficult to resist the conclusion that the WHI investigators have been doing everything they could to wring the bleakest possible interpretation from their recalcitrant data," Drs. Bluming and Tavris write.
Although concerns about breast cancer and other health risks are valid, "HRT is not the clear and present danger that the WHI and much of the media have made it out to be," Drs. Bluming and Tavris conclude. They contend that the weight of available evidence supports the use of HRT by women who are having menopausal symptoms, beginning at the start of menopause and continuing for as many years as necessary.
About The Cancer Journal
The Cancer Journal: The Journal of Principles & Practice of Oncology provides an integrated view of modern oncology across all disciplines. The Journal publishes original research and reviews, and also serves to update the content published in the textbook Cancer: Principles & Practice of Oncology
About Lippincott Williams & Wilkins
Lippincott Williams & Wilkins (LWW) is a leading international publisher for healthcare professionals and students with nearly 300 periodicals and 1,500 books in more than 100 disciplines publishing under the LWW brand, as well as content-based sites and online corporate and customer services. LWW is part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry.
Wolters Kluwer Health is a division of Wolters Kluwer, a leading global information services and publishing company. The company provides products and services for professionals in the health, tax, accounting, corporate, financial services, legal, and regulatory sectors. Wolters Kluwer had 2008 annual revenues of €3.4 billion ($4.9 billion), employs approximately 20,000 people worldwide, and maintains operations in over 35 countries across Europe, North America, Asia Pacific, and Latin America. Wolters Kluwer is headquartered in Amsterdam, the Netherlands. Its shares are quoted on Euronext Amsterdam (WKL) and are included in the AEX and Euronext 100 indices.
Source: Wolters Kluwer Health
четверг, 23 июня 2011 г.
среда, 22 июня 2011 г.
Kansas Breast And Cervical Cancer Screening Program For Low-Income, Uninsured Women Runs Out Of Funding
The Kansas Early Detection Works program, which provides uninsured low-income women in the state with breast and cervical cancer screenings at no cost, has depleted its operating funds and will delay almost all cancer screenings until July 1, the Wichita Eagle reports. Janet Neff, director of the Cancer Prevention and Control Program at the Kansas Department of Health and Environment, said the program has received about $2.3 million annually in recent years from CDC. The program also receives some funding from the state and the Mid-Kansas affiliate of the Susan G. Komen for the Cure Foundation.
The screening program depleted its funds in March. However, program officials reserved a limited amount of funding to provide diagnostic tests until the new fiscal year begins on July 1 to women who display symptoms of breast or cervical cancer. Women who inquire about the program will be placed on a waiting list and will be screened when funding becomes available. Kansas women ages 40 to 64 who are uninsured and meet income guidelines are eligible for the program. According to Neff, about 5,800 of the at least 27,000 women in Kansas who qualify to receive no-cost screenings have done so since July 1, 2007.
Neff said she requested slightly more than $2.3 million in federal funds for FY 2009 (Shideler, Wichita Eagle, 5/5).
Reprinted with kind 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.
© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
The screening program depleted its funds in March. However, program officials reserved a limited amount of funding to provide diagnostic tests until the new fiscal year begins on July 1 to women who display symptoms of breast or cervical cancer. Women who inquire about the program will be placed on a waiting list and will be screened when funding becomes available. Kansas women ages 40 to 64 who are uninsured and meet income guidelines are eligible for the program. According to Neff, about 5,800 of the at least 27,000 women in Kansas who qualify to receive no-cost screenings have done so since July 1, 2007.
Neff said she requested slightly more than $2.3 million in federal funds for FY 2009 (Shideler, Wichita Eagle, 5/5).
Reprinted with kind 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.
© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
вторник, 21 июня 2011 г.
Industry-funded Breast Cancer Trials More Likely To Yield Positive Results
Industry-funded studies of breast cancer therapies are more likely to report positive results than non-pharmaceutical funded studies, researchers from the University of North Carolina at Chapel Hill and the Dana Farber Cancer Institute have found. In addition, significant differences exist in the design and nature of clinical trials supported by the pharmaceutical industry compared to trials without industry involvement.
Published online Monday (Feb. 26) in Cancer, the journal of the American Cancer Society, the study explores the impact of pharmaceutical-company involvement on breast cancer clinical trial design and outcome. Drug-industry investment in research now exceeds the operating budget of the National Institutes of Health and previous studies have examined the impact on other areas of clinical medicine, but not breast cancer.
"Our study shines a flashlight on the issue of the rising role and potential impact of the pharmaceutical industry on breast cancer research and highlights important questions that need to be addressed through further research," said Dr. Jeffrey Peppercorn, assistant professor of medicine in UNC School of Medicine's division of hematology and oncology and a member of the UNC Lineberger Comprehensive Cancer Center.
"The significance of our study is not to say that the drug industry does anything wrong they are excellent at developing new therapies, and there are many recent examples in breast cancer research. But if more and more research is funded by drug companies, then the limited amount of funding coming from other sources may need to be directed to address other questions," Peppercorn said.
The researchers reviewed all breast cancer clinical trials published in 10 English-language medical journals in the years 1993, 1998 and 2003. They focused their formal statistical analysis on the 2003 trials because the identification of industry funded or non-industry funded research was likely more accurate due to more stringent disclosure guidelines than earlier periods.
Trials with industry involvement were more likely than non-industry studies to use a single-arm study design, without a comparison group. This isn't surprising, Peppercorn notes, because these studies are a key step in drug development.
In 2003, 57 percent of studies reported pharmaceutical involvement. Of these, 66 percent were single-arm studies. Only 33 percent of non-industry studies used single-arm design.
The industry studies were also more likely to yield positive results; 84 percent of industry-supported studies showed positive results, compared with 54 percent of non-industry studies.
"It's been seen again and again in various branches of clinical medicine that studies that involve pharmaceutical industry sponsorship are more likely to have positive outcomes," Peppercorn said. "It's not fair to say at this point that it's necessarily related to biased interpretation of results." For instance, another explanation could be that industry makes smarter or safer choices about what drugs are brought to trial.
However, as industry funding becomes an increasingly dominant source of research funding, clinical questions that aren't directly related to drug development may be neglected, Peppercorn said. Such questions include the optimal duration for giving a medication or whether certain groups of patients benefit from a medication more than others, he said.
Study co-authors are Emily Blood, Dr. Eric Winer and Dr. Ann Partridge, all of the Dana Farber Cancer Institute, where Dr. Peppercorn received his training and initiated the study.
University of North Carolina at Chapel Hill School of Medicine
101 Manning Dr., 6002 East Wing
Chapel Hill, NC 27514
United States
med.unc
Published online Monday (Feb. 26) in Cancer, the journal of the American Cancer Society, the study explores the impact of pharmaceutical-company involvement on breast cancer clinical trial design and outcome. Drug-industry investment in research now exceeds the operating budget of the National Institutes of Health and previous studies have examined the impact on other areas of clinical medicine, but not breast cancer.
"Our study shines a flashlight on the issue of the rising role and potential impact of the pharmaceutical industry on breast cancer research and highlights important questions that need to be addressed through further research," said Dr. Jeffrey Peppercorn, assistant professor of medicine in UNC School of Medicine's division of hematology and oncology and a member of the UNC Lineberger Comprehensive Cancer Center.
"The significance of our study is not to say that the drug industry does anything wrong they are excellent at developing new therapies, and there are many recent examples in breast cancer research. But if more and more research is funded by drug companies, then the limited amount of funding coming from other sources may need to be directed to address other questions," Peppercorn said.
The researchers reviewed all breast cancer clinical trials published in 10 English-language medical journals in the years 1993, 1998 and 2003. They focused their formal statistical analysis on the 2003 trials because the identification of industry funded or non-industry funded research was likely more accurate due to more stringent disclosure guidelines than earlier periods.
Trials with industry involvement were more likely than non-industry studies to use a single-arm study design, without a comparison group. This isn't surprising, Peppercorn notes, because these studies are a key step in drug development.
In 2003, 57 percent of studies reported pharmaceutical involvement. Of these, 66 percent were single-arm studies. Only 33 percent of non-industry studies used single-arm design.
The industry studies were also more likely to yield positive results; 84 percent of industry-supported studies showed positive results, compared with 54 percent of non-industry studies.
"It's been seen again and again in various branches of clinical medicine that studies that involve pharmaceutical industry sponsorship are more likely to have positive outcomes," Peppercorn said. "It's not fair to say at this point that it's necessarily related to biased interpretation of results." For instance, another explanation could be that industry makes smarter or safer choices about what drugs are brought to trial.
However, as industry funding becomes an increasingly dominant source of research funding, clinical questions that aren't directly related to drug development may be neglected, Peppercorn said. Such questions include the optimal duration for giving a medication or whether certain groups of patients benefit from a medication more than others, he said.
Study co-authors are Emily Blood, Dr. Eric Winer and Dr. Ann Partridge, all of the Dana Farber Cancer Institute, where Dr. Peppercorn received his training and initiated the study.
University of North Carolina at Chapel Hill School of Medicine
101 Manning Dr., 6002 East Wing
Chapel Hill, NC 27514
United States
med.unc
понедельник, 20 июня 2011 г.
Lapatinib Could Be Beneficial In Treating Patients With Aggressive Inflammatory Breast Cancer
An article published online First and in the June edition of The lancet Oncology reports the findings of a phase II study on inflammatory breast cancer, an aggressive form of the disease representing up to one tenth of malignant breast cancer cases. Dr Stephen Johnston, Royal Marsden Hospital, London, UK, and Dr Bella Kaufman, The Chaim Sheba Medical Center, Tel Hashomer, Israel, and colleagues discuss how lapatinib may be beneficial in the treatment of this form of cancer.
In inflammatory breast cancer, the protein epidermal growth factor receptor 2 (HER2) implicated in the signaling pathways leading to cell growth is manifested much more than in other less aggressive cancers. This disease makes up one to six percent of all invasive breast tumors in Western Europe and the USA and five to ten percent in North Africa and Arabian countries. The clinical symptoms are: rapid onset of swelling, redness of the breast skin, fluid under the skin of more than two thirds of the breast resulting in a bumpy appearance, painfulness, hardening and warming of the breast.
Lapatinib hinders tumor growth because it is an oral inhibitor of HER2. Options are limited for patients with resistance to conventional anthracycline or taxane and trastuzumab treatment. The study included 126 patients receiving a daily dose of lapatinib (1,500 mg). Every four weeks, skin disease was evaluated and cancer evolution (local and secondary) was assessed using standard criteria.
Findings showed that none of the patients had an absolute response to the treatment but 39 percent (49 patients) had a partial response with a 50 percent healing in extent of skin disease from baseline. The average progression-free survival was of fifteen weeks, with an average duration of response of twenty one weeks. Six months later, 22 percent of patients were still progression-free. The probability of response to lapatinib was not altered by prior treatment with trastuzumab. The general average of survival was accounted for four groups of patients:
• 33 patients who responded to lapatinib and had previous treatment with trastuzumab. Median survival: 18.4 months.
• 15 patients who responded to lapatinib and had no previous treatment with trastuzumab. Median survival: 14.0 months.
• 61 patients unresponsive to lapatinib and previous treatment with trastuzumab. Median survival: 8.4 months.
• 16 patients unresponsive to lapatinib with no previous trastuzumab treatment. Median survival: 8.2 months.
Undesirable events were frequent since 92 percent of patients experienced at least one. Although the majority was not considered linked to lapatinib, 32 percent of patients suffered serious adverse events: eight of them experienced shortness of breath, and six of them had fluid around the lungs. There were five deaths from adverse events that were possibly treatment related.
The researchers point out: "Patients who responded to treatment with lapatinib had a longer median overall survival than did those patients who did not respond, irrespective of previous exposure to trastuzumab. Patients exposed to previous trastuzumab treatment who experienced a response to lapatinib had the longest median overall survival. This finding confirms the clinical benefit of targeted therapy in these patients."
They write in conclusion: "Lapatinib monotherapy is potentially clinically effective in heavily pretreated patients with inflammatory breast cancer with HER2+ tumours. The objective response rate noted...coupled with the median duration of response and median overall survival supports a role for lapatinib in these patients."
thelancet
Written by Stephanie Brunner (B.A.)
In inflammatory breast cancer, the protein epidermal growth factor receptor 2 (HER2) implicated in the signaling pathways leading to cell growth is manifested much more than in other less aggressive cancers. This disease makes up one to six percent of all invasive breast tumors in Western Europe and the USA and five to ten percent in North Africa and Arabian countries. The clinical symptoms are: rapid onset of swelling, redness of the breast skin, fluid under the skin of more than two thirds of the breast resulting in a bumpy appearance, painfulness, hardening and warming of the breast.
Lapatinib hinders tumor growth because it is an oral inhibitor of HER2. Options are limited for patients with resistance to conventional anthracycline or taxane and trastuzumab treatment. The study included 126 patients receiving a daily dose of lapatinib (1,500 mg). Every four weeks, skin disease was evaluated and cancer evolution (local and secondary) was assessed using standard criteria.
Findings showed that none of the patients had an absolute response to the treatment but 39 percent (49 patients) had a partial response with a 50 percent healing in extent of skin disease from baseline. The average progression-free survival was of fifteen weeks, with an average duration of response of twenty one weeks. Six months later, 22 percent of patients were still progression-free. The probability of response to lapatinib was not altered by prior treatment with trastuzumab. The general average of survival was accounted for four groups of patients:
• 33 patients who responded to lapatinib and had previous treatment with trastuzumab. Median survival: 18.4 months.
• 15 patients who responded to lapatinib and had no previous treatment with trastuzumab. Median survival: 14.0 months.
• 61 patients unresponsive to lapatinib and previous treatment with trastuzumab. Median survival: 8.4 months.
• 16 patients unresponsive to lapatinib with no previous trastuzumab treatment. Median survival: 8.2 months.
Undesirable events were frequent since 92 percent of patients experienced at least one. Although the majority was not considered linked to lapatinib, 32 percent of patients suffered serious adverse events: eight of them experienced shortness of breath, and six of them had fluid around the lungs. There were five deaths from adverse events that were possibly treatment related.
The researchers point out: "Patients who responded to treatment with lapatinib had a longer median overall survival than did those patients who did not respond, irrespective of previous exposure to trastuzumab. Patients exposed to previous trastuzumab treatment who experienced a response to lapatinib had the longest median overall survival. This finding confirms the clinical benefit of targeted therapy in these patients."
They write in conclusion: "Lapatinib monotherapy is potentially clinically effective in heavily pretreated patients with inflammatory breast cancer with HER2+ tumours. The objective response rate noted...coupled with the median duration of response and median overall survival supports a role for lapatinib in these patients."
thelancet
Written by Stephanie Brunner (B.A.)
воскресенье, 19 июня 2011 г.
To Escape Death By Hormonal Therapy Breast Cancer Cells Recycle
Many breast cancer cells facing potentially lethal antiestrogen therapy recycle to survive, researchers say.
About 70 percent of breast cancer cells have receptors for the hormone estrogen, which acts as a nutrient and stimulates their growth. Patients typically get an antiestrogen such as tamoxifen for five years to try to starve them to death, says Dr. Patricia V. Schoenlein, cancer researcher in the Medical College of Georgia Schools of Medicine and Graduate Studies.
"About 50 to 60 percent of these women really benefit from hormonal therapy," says Dr. Schoenlein. Why others don't has been asked for at least two decades.
One reason may be breast cancer cells switch into a survival mode that normal cells also use when faced with starvation, according to research published in the September issue of Molecular Cancer Therapeutics. Dr. Schoenlein also is reporting on the research during the 2nd World Conference on Magic Bullets (Ehrlich II) Oct. 3-5 in NГјrenberg, Germany.
It's called macroautophagy - autophagy means "self eating" - and within a week, breast cancer cells can reorganize component parts, degrade non-essentials and live in this state until antiestrogen therapy is stopped or the cells mutate and resume proliferation in the presence of tamoxifen. "It's like taking your foot off of the gas pedal of your car," says Dr. Schoenlein, corresponding author on the study. "The cancer cell is in idle, unable to grow or replicate. But the cell is smart enough to use component parts generated by macroautophagy for the most necessary things required for survival." She notes that macroautophagy can't be maintained indefinitely; cells can actually self-digest. "This is a time-buying strategy."
Chemotherapeutic drugs are more direct killers but also kill healthy cells and can be tolerated by patients only for relatively short periods. Antiestrogen therapy is more specific, targeting breast cancer cells that express estrogen receptors.
In the laboratory, 20-25 percent of breast cancer cells died when Dr. Schoenlein and colleagues gave antiestrogen continuously over time - similar to how patients get it. More typically, the cells expressed increasing levels of macroautophagy and survived. "They don't grow, but they survive the therapy. They will grow if you take away the therapy." Adding a macroautophagy inhibitor promoted robust cell death.
"We believe targeting the autophagosome function will significantly improve the efficacy of hormonal treatment for estrogen-positive breast cancer," says the researcher. She recently received a three-year, $1.1 million National Cancer Institute grant to pursue that strategy.
She'll now look for ways to block macroautophagy in an animal model, including using chloroquine, a drug used to treat malaria. "We know patients can take it with few side effects," she says. If it works in animals, the drug, in combination with an antiestrogen, could move relatively quickly into human testing.
During autophagy, the internal pH for the recycling center of the reorganized cell gets acidic and chloroquine increases pH. "If you add this particular inhibitor of the recycling center, you alter the pH and block its ability to do what it is supposed to do," says Dr. Schoenlein.
A University of Pennsylvania team led by Dr. Craig Thompson reported in 2007 in The Journal of Clinical Investigation that chloroquine increased death of suicide-resistant lymphoma cells being treated with chemotherapy. Dr. Schoenlein will give chloroquine along with an antiestrogen and measure cell death.
"Most cancers probably use autophagy as a survival mechanism. You can either block the autophagosome with your therapy or you can make the cell eat itself to the point of no return and the cell self-destructs. You have to push it either way," she says. Although there are no known compounds in clinical use to induce self-destruction by autophagy, there is some evidence arsenic trioxide, a compound used in China to treat some aggressive cancers, prompts cancer cells to die from self digestion, she says. That and other compounds will no doubt be studied further, she says.
Dr. Schoenlein believes breast cancer survival during macroautophagy requires high activity of the tumor suppressor protein Rb and low levels of the lipid ceramide. Ceramide is vital but causes cell death at high levels. MCG researcher Erhard Bieberich and colleague Dr. Brian G. Condie at the University of Georgia showed in 2003 that high levels of ceramide kill cells that are unnecessary to the developing brain. The new studies will further explore the roles of Rb and ceramide in breast cancer survival during macroautophagy and determine if chloroquine can change their balance.
MCG news categories related to this story:
Cancer
School of Medicine
School of Graduate Studies
Source: Toni Baker
Medical College of Georgia
About 70 percent of breast cancer cells have receptors for the hormone estrogen, which acts as a nutrient and stimulates their growth. Patients typically get an antiestrogen such as tamoxifen for five years to try to starve them to death, says Dr. Patricia V. Schoenlein, cancer researcher in the Medical College of Georgia Schools of Medicine and Graduate Studies.
"About 50 to 60 percent of these women really benefit from hormonal therapy," says Dr. Schoenlein. Why others don't has been asked for at least two decades.
One reason may be breast cancer cells switch into a survival mode that normal cells also use when faced with starvation, according to research published in the September issue of Molecular Cancer Therapeutics. Dr. Schoenlein also is reporting on the research during the 2nd World Conference on Magic Bullets (Ehrlich II) Oct. 3-5 in NГјrenberg, Germany.
It's called macroautophagy - autophagy means "self eating" - and within a week, breast cancer cells can reorganize component parts, degrade non-essentials and live in this state until antiestrogen therapy is stopped or the cells mutate and resume proliferation in the presence of tamoxifen. "It's like taking your foot off of the gas pedal of your car," says Dr. Schoenlein, corresponding author on the study. "The cancer cell is in idle, unable to grow or replicate. But the cell is smart enough to use component parts generated by macroautophagy for the most necessary things required for survival." She notes that macroautophagy can't be maintained indefinitely; cells can actually self-digest. "This is a time-buying strategy."
Chemotherapeutic drugs are more direct killers but also kill healthy cells and can be tolerated by patients only for relatively short periods. Antiestrogen therapy is more specific, targeting breast cancer cells that express estrogen receptors.
In the laboratory, 20-25 percent of breast cancer cells died when Dr. Schoenlein and colleagues gave antiestrogen continuously over time - similar to how patients get it. More typically, the cells expressed increasing levels of macroautophagy and survived. "They don't grow, but they survive the therapy. They will grow if you take away the therapy." Adding a macroautophagy inhibitor promoted robust cell death.
"We believe targeting the autophagosome function will significantly improve the efficacy of hormonal treatment for estrogen-positive breast cancer," says the researcher. She recently received a three-year, $1.1 million National Cancer Institute grant to pursue that strategy.
She'll now look for ways to block macroautophagy in an animal model, including using chloroquine, a drug used to treat malaria. "We know patients can take it with few side effects," she says. If it works in animals, the drug, in combination with an antiestrogen, could move relatively quickly into human testing.
During autophagy, the internal pH for the recycling center of the reorganized cell gets acidic and chloroquine increases pH. "If you add this particular inhibitor of the recycling center, you alter the pH and block its ability to do what it is supposed to do," says Dr. Schoenlein.
A University of Pennsylvania team led by Dr. Craig Thompson reported in 2007 in The Journal of Clinical Investigation that chloroquine increased death of suicide-resistant lymphoma cells being treated with chemotherapy. Dr. Schoenlein will give chloroquine along with an antiestrogen and measure cell death.
"Most cancers probably use autophagy as a survival mechanism. You can either block the autophagosome with your therapy or you can make the cell eat itself to the point of no return and the cell self-destructs. You have to push it either way," she says. Although there are no known compounds in clinical use to induce self-destruction by autophagy, there is some evidence arsenic trioxide, a compound used in China to treat some aggressive cancers, prompts cancer cells to die from self digestion, she says. That and other compounds will no doubt be studied further, she says.
Dr. Schoenlein believes breast cancer survival during macroautophagy requires high activity of the tumor suppressor protein Rb and low levels of the lipid ceramide. Ceramide is vital but causes cell death at high levels. MCG researcher Erhard Bieberich and colleague Dr. Brian G. Condie at the University of Georgia showed in 2003 that high levels of ceramide kill cells that are unnecessary to the developing brain. The new studies will further explore the roles of Rb and ceramide in breast cancer survival during macroautophagy and determine if chloroquine can change their balance.
MCG news categories related to this story:
Cancer
School of Medicine
School of Graduate Studies
Source: Toni Baker
Medical College of Georgia
суббота, 18 июня 2011 г.
More Complete View Of Breast Cancer Gene Mutations In US Population: New Findings
A large study funded by the National Institutes of Health today provided the clearest picture yet of the prevalence in the U.S. population of mutations in two genes associated with an increased risk of breast cancer. The genes are called Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2). In addition, the study identified key predictors for assessing which women are most likely to carry these genetic mutations.
Each year, approximately 200,000 women in the United States are diagnosed with breast cancer. The majority of breast cancer cases are caused by genetic changes that occur during a woman's lifetime and not by genetic mutations inherited from her parents. However, researchers estimate that inherited mutations play a role in anywhere from 5 to 27 percent of all breast cancer cases. In the mid 1990s, researchers found that mutations in the BRCA1 and BRCA2 genes are a major cause of the hereditary form of the disease. Women inheriting these mutations have a 40 to 85 percent lifetime risk of developing breast cancer, as well as an increased risk of ovarian cancer.
To date, most of the studies on BRCA1 and BRCA2 mutations have focused on families known to be at high risk for breast cancer and on women who develop breast cancer at a relatively young age. The new study, published today in the journal Cancer Research, looked at the prevalence and predictors of BRCA1 and BRCA2 mutations in under-studied groups of women, such as African Americans and older women.
"Studies of any notable size have focused almost exclusively on white women and young women. This research clearly was needed to improve our means of assessing the likelihood of carrying BRCA1 and BRCA2 mutations in a wider spectrum of women," said one of the study's lead investigators, Elaine Ostrander, Ph.D., chief of the Cancer Genetics Branch in the National Human Genome Research Institute's Division of Intramural Research. Dr. Ostrander was previously head of the genetics program at the Fred Hutchinson Cancer Research Center, which is the institution that led the study.
The researchers examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 similar women without breast cancer, all of whom were participants in the National Institute of Child Health and Human Development's (NICHD's) Women's Contraceptive And Reproductive Experiences (CARE) study. The women involved in the study were white and African American women, ages 35 to 64, who lived in the Atlanta, Detroit, Los Angeles, Philadelphia and Seattle metropolitan areas.
"The advantages of this study include its large sample size, inclusion of under-studied groups of women and the fact that the results are population based," said one of the study's co-authors, Robert Spirtas, Dr.P.H, former chief of NICHD's Contraception and Reproductive Health Branch and now retired.
Researchers found that 2.4 percent of the breast cancer patients had BRCA1 mutations and 2.3 percent had BRCA2 mutations. BRCA1 mutations were more common among white breast cancer patients (2.9 percent) than among African American patients (1.4 percent). Breast cancer patients of Jewish ancestry were also significantly more likely to have BRCA1 mutations than non-Jewish patients - 10.2 percent compared to 2.0 percent. For BRCA2, African American patients were slightly more likely to have mutations, 2.6 percent, than were white patients, 2.1 percent.
Based on their findings, the researchers went on to calculate the prevalence of BRCA1 and BRCA2 mutations in the general U.S. population. Among white and African American women ages 35 to 64, the prevalence of BRCA1 mutations is 0.06 percent and the prevalence of BRCA2 mutations is 0.4 percent, the researchers estimated.
"These findings from our large, population-based study are compatible with earlier estimates made by extrapolating from smaller studies. However, we found a slightly lower frequency of BRCA1 mutations and a higher frequency of BRCA2 mutations," said the study's other lead investigator, Kathleen Malone, Ph.D., Member of the Public Health Sciences Division at the Fred Hutchinson Cancer Center. "We think the difference lies in the fact that earlier studies were confined mainly to whites, and that African American women carry BRCA2 mutations more often than white women."
The researchers also identified key predictors of whether a woman with breast cancer is likely to carry a BRCA1 or BRCA2 mutation. Such information is important because it can help to improve means of assessing which women may benefit the most from genetic testing, increased breast cancer screening and other measures aimed at early detection, treatment or prevention. The most significant predictors for BRCA1 mutations were: Jewish ancestry, a family history of ovarian cancer and a family history of breast cancer occurring before age 45.
For BRCA2 mutations, researchers uncovered fewer predictors, and they had more modest effects. Among the breast cancer patients studied, the only significant predictors of a BRCA2 mutation were early age of onset (before age 45) in the patient herself or early onset of breast cancer in mother, sisters, grandmothers or aunts.
"These findings underscore why women need to learn as much as they can about their family health history and then share that information with their health-care professionals. However, it must be emphasized that the presence or absence of a predictive factor does not automatically equate with a high or low likelihood of carrying a breast cancer gene mutation," said NIH Director Elias A. Zerhouni, M.D. "The majority of women with breast cancer - even those with a family history of the disease - do not carry mutations in these genes. These predictors need to be considered in the context of each woman's complete family health history."
In addition to the Fred Hutchinson Cancer Center, NHGRI and NICHD, the team included researchers from the National Cancer Institute; Bay State Medical Center, Springfield, Mass.; the University of Pennsylvania, Philadelphia; University of Southern California, Los Angeles; and Wayne State University, Detroit.
About NIH
The National Cancer Institute, the National Institute of Child Health and Human Development, and the National Human Genome Research Institute are among the 27 institutes and centers that make up the National Institutes of Health (NIH) - The Nation's Medical Research Agency. NIH is a component of the U. S. Department of Health and Human Services (HHS). It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.
How to Create a Family Health History
To help people in the task of creating their family health histories, HHS offers a free, computerized tool that organizes health information into a printout that can be can taken to health-care professionals. The tool, called "My Family Health Portrait," is available at https://familyhistory.hhs/.
Contact: Geoff Spencer
NIH/National Human Genome Research Institute
Each year, approximately 200,000 women in the United States are diagnosed with breast cancer. The majority of breast cancer cases are caused by genetic changes that occur during a woman's lifetime and not by genetic mutations inherited from her parents. However, researchers estimate that inherited mutations play a role in anywhere from 5 to 27 percent of all breast cancer cases. In the mid 1990s, researchers found that mutations in the BRCA1 and BRCA2 genes are a major cause of the hereditary form of the disease. Women inheriting these mutations have a 40 to 85 percent lifetime risk of developing breast cancer, as well as an increased risk of ovarian cancer.
To date, most of the studies on BRCA1 and BRCA2 mutations have focused on families known to be at high risk for breast cancer and on women who develop breast cancer at a relatively young age. The new study, published today in the journal Cancer Research, looked at the prevalence and predictors of BRCA1 and BRCA2 mutations in under-studied groups of women, such as African Americans and older women.
"Studies of any notable size have focused almost exclusively on white women and young women. This research clearly was needed to improve our means of assessing the likelihood of carrying BRCA1 and BRCA2 mutations in a wider spectrum of women," said one of the study's lead investigators, Elaine Ostrander, Ph.D., chief of the Cancer Genetics Branch in the National Human Genome Research Institute's Division of Intramural Research. Dr. Ostrander was previously head of the genetics program at the Fred Hutchinson Cancer Research Center, which is the institution that led the study.
The researchers examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 similar women without breast cancer, all of whom were participants in the National Institute of Child Health and Human Development's (NICHD's) Women's Contraceptive And Reproductive Experiences (CARE) study. The women involved in the study were white and African American women, ages 35 to 64, who lived in the Atlanta, Detroit, Los Angeles, Philadelphia and Seattle metropolitan areas.
"The advantages of this study include its large sample size, inclusion of under-studied groups of women and the fact that the results are population based," said one of the study's co-authors, Robert Spirtas, Dr.P.H, former chief of NICHD's Contraception and Reproductive Health Branch and now retired.
Researchers found that 2.4 percent of the breast cancer patients had BRCA1 mutations and 2.3 percent had BRCA2 mutations. BRCA1 mutations were more common among white breast cancer patients (2.9 percent) than among African American patients (1.4 percent). Breast cancer patients of Jewish ancestry were also significantly more likely to have BRCA1 mutations than non-Jewish patients - 10.2 percent compared to 2.0 percent. For BRCA2, African American patients were slightly more likely to have mutations, 2.6 percent, than were white patients, 2.1 percent.
Based on their findings, the researchers went on to calculate the prevalence of BRCA1 and BRCA2 mutations in the general U.S. population. Among white and African American women ages 35 to 64, the prevalence of BRCA1 mutations is 0.06 percent and the prevalence of BRCA2 mutations is 0.4 percent, the researchers estimated.
"These findings from our large, population-based study are compatible with earlier estimates made by extrapolating from smaller studies. However, we found a slightly lower frequency of BRCA1 mutations and a higher frequency of BRCA2 mutations," said the study's other lead investigator, Kathleen Malone, Ph.D., Member of the Public Health Sciences Division at the Fred Hutchinson Cancer Center. "We think the difference lies in the fact that earlier studies were confined mainly to whites, and that African American women carry BRCA2 mutations more often than white women."
The researchers also identified key predictors of whether a woman with breast cancer is likely to carry a BRCA1 or BRCA2 mutation. Such information is important because it can help to improve means of assessing which women may benefit the most from genetic testing, increased breast cancer screening and other measures aimed at early detection, treatment or prevention. The most significant predictors for BRCA1 mutations were: Jewish ancestry, a family history of ovarian cancer and a family history of breast cancer occurring before age 45.
For BRCA2 mutations, researchers uncovered fewer predictors, and they had more modest effects. Among the breast cancer patients studied, the only significant predictors of a BRCA2 mutation were early age of onset (before age 45) in the patient herself or early onset of breast cancer in mother, sisters, grandmothers or aunts.
"These findings underscore why women need to learn as much as they can about their family health history and then share that information with their health-care professionals. However, it must be emphasized that the presence or absence of a predictive factor does not automatically equate with a high or low likelihood of carrying a breast cancer gene mutation," said NIH Director Elias A. Zerhouni, M.D. "The majority of women with breast cancer - even those with a family history of the disease - do not carry mutations in these genes. These predictors need to be considered in the context of each woman's complete family health history."
In addition to the Fred Hutchinson Cancer Center, NHGRI and NICHD, the team included researchers from the National Cancer Institute; Bay State Medical Center, Springfield, Mass.; the University of Pennsylvania, Philadelphia; University of Southern California, Los Angeles; and Wayne State University, Detroit.
About NIH
The National Cancer Institute, the National Institute of Child Health and Human Development, and the National Human Genome Research Institute are among the 27 institutes and centers that make up the National Institutes of Health (NIH) - The Nation's Medical Research Agency. NIH is a component of the U. S. Department of Health and Human Services (HHS). It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.
How to Create a Family Health History
To help people in the task of creating their family health histories, HHS offers a free, computerized tool that organizes health information into a printout that can be can taken to health-care professionals. The tool, called "My Family Health Portrait," is available at https://familyhistory.hhs/.
Contact: Geoff Spencer
NIH/National Human Genome Research Institute
пятница, 17 июня 2011 г.
Study Finds Race Affects African American Survival Of Breast Cancer
African-American women with breast cancer were more likely to have larger, later-stage tumors that were more difficult to treat and also had lower survival rates than Hispanic and Caucasian women who received the same treatment in two independent series of clinical trials examined by researchers from The University of Texas M. D. Anderson Cancer Center.
The analysis published on line Oct. 23 by Cancer, a peer-reviewed journal of the American Cancer Society, indicates that race is associated with unfavorable tumor biology, which, along with other factors, likely contributes to the lower rate of breast cancer survival among African-Americans.
"These findings should prompt additional research on how we can improve outcomes for African-American patients by understanding and addressing tumor biology," says first author Wendy Woodward, M.D., Ph.D., assistant professor of radiation oncology at M. D. Anderson. "It's important to identify unique features in different populations and subgroups of all women with breast cancer so we can understand a woman's risk and factors that affect her care on an individual level."
African-American women are less likely than Caucasian women to have breast cancer but are more likely to die from it. Many factors have been implicated in this disparity, the researchers note, including access to health care and screening, differing treatments, socioeconomic status and racial bias.
By examining two series of clinical trials in which treatment was specified and rigorously followed for all patients, the research team minimized biases related to access to care and type of treatment, two variables that often confound analysis of the issue.
Between 1975 and 2000, 2,140 breast cancer patients were treated in two prospective series of clinical trials at M. D. Anderson involving use of the chemotherapy doxorubicin before and after a radical or modified radical mastectomy.
Of the total patients, 1,590 were Caucasian, 300 were Hispanic, and 250 were African-American, with racial categories based on self-reporting by the patients. In both trials, African-American women received at least as many cycles of chemotherapy as did Hispanics and Caucasians.
In the clinical trial for post-operative chemotherapy, the 10-year overall survival rate for African-Americans was 52 percent. For Hispanics and Caucasians it was 62 percent.
More African-American women came to the trial with later stage disease (24 percent compared with 18 percent of Hispanics and 16 percent of Caucasians) and tumors greater than 5 centimeters (22 percent compared with 13 percent each for Hispanic and Caucasians). African-Americans were more likely to have tumors that were estrogen-receptor negative, which are considered more difficult to treat (41 percent compared with 32 percent for Hispanics and 33 percent for Caucasians).
The trial of pre-operative chemotherapy showed similar results, with African-American 10-year survival rate of 40 percent, compared with 56 percent for Hispanics and 54 percent for Caucasians. As in the post-operative trial, higher percentages of African-Americans came to the trial with later-stage disease, larger tumors, and estrogen-receptor negative disease.
A multivariable analysis that took into account age, estrogen receptor-negative status, primary tumor size, and whether the disease had spread to the lymph nodes, showed that African-American race is an independent factor in reduced overall survival rate.
The researchers note they could not take into account factors that might have influenced the patients' care before they entered the clinical trials. And their analysis did not include socioeconomic factors because that information was not available for patients. However, they doubt socioeconomic factors could fully explain differences in survival rate because Hispanic and African-American women have similar socioeconomic status in M. D. Anderson's patient referral area.
"We interpret these data as suggesting that intrinsic biological differences in the disease and response to treatment among racial groups contributed to the poorer overall survival rates seen in the African-American cohorts," the researchers conclude.
"It's important to note that African-Americans, and people in all self-reported racial groups, are genetically and culturally diverse," Woodward says. "Not all African-American women will have worse survival prospects for breast cancer, but there are probably subsets of patients for whom we could be doing something better.
"The tools and technology are emerging that will allow us to understand how one person's tumors differ from another and how we can more effectively assign people to treatments," Woodward says.
The paper notes that explaining the association of African-American race with more aggressive breast cancer will be challenging, and suggests analysis of genetic variation and regulation of genes by environmental factors as two potential areas of research.
Co-authors with Woodward, all from M. D. Anderson, are: Eugene Huang, M.D., Marsha McNeese, M.D., George Perkins, M.D., Eric Strom, M.D., and senior author Thomas Buchholz, M.D., all of the Department of Radiation Oncology; Susan Tucker, M.D., Department of Biostatistics; Lavinia Middleton, M.D., Department of Pathology; and Karen Hahn, M.D., and Gabriel Hortobagyi, M.D., Department of Breast Medical Oncology.
Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center
The analysis published on line Oct. 23 by Cancer, a peer-reviewed journal of the American Cancer Society, indicates that race is associated with unfavorable tumor biology, which, along with other factors, likely contributes to the lower rate of breast cancer survival among African-Americans.
"These findings should prompt additional research on how we can improve outcomes for African-American patients by understanding and addressing tumor biology," says first author Wendy Woodward, M.D., Ph.D., assistant professor of radiation oncology at M. D. Anderson. "It's important to identify unique features in different populations and subgroups of all women with breast cancer so we can understand a woman's risk and factors that affect her care on an individual level."
African-American women are less likely than Caucasian women to have breast cancer but are more likely to die from it. Many factors have been implicated in this disparity, the researchers note, including access to health care and screening, differing treatments, socioeconomic status and racial bias.
By examining two series of clinical trials in which treatment was specified and rigorously followed for all patients, the research team minimized biases related to access to care and type of treatment, two variables that often confound analysis of the issue.
Between 1975 and 2000, 2,140 breast cancer patients were treated in two prospective series of clinical trials at M. D. Anderson involving use of the chemotherapy doxorubicin before and after a radical or modified radical mastectomy.
Of the total patients, 1,590 were Caucasian, 300 were Hispanic, and 250 were African-American, with racial categories based on self-reporting by the patients. In both trials, African-American women received at least as many cycles of chemotherapy as did Hispanics and Caucasians.
In the clinical trial for post-operative chemotherapy, the 10-year overall survival rate for African-Americans was 52 percent. For Hispanics and Caucasians it was 62 percent.
More African-American women came to the trial with later stage disease (24 percent compared with 18 percent of Hispanics and 16 percent of Caucasians) and tumors greater than 5 centimeters (22 percent compared with 13 percent each for Hispanic and Caucasians). African-Americans were more likely to have tumors that were estrogen-receptor negative, which are considered more difficult to treat (41 percent compared with 32 percent for Hispanics and 33 percent for Caucasians).
The trial of pre-operative chemotherapy showed similar results, with African-American 10-year survival rate of 40 percent, compared with 56 percent for Hispanics and 54 percent for Caucasians. As in the post-operative trial, higher percentages of African-Americans came to the trial with later-stage disease, larger tumors, and estrogen-receptor negative disease.
A multivariable analysis that took into account age, estrogen receptor-negative status, primary tumor size, and whether the disease had spread to the lymph nodes, showed that African-American race is an independent factor in reduced overall survival rate.
The researchers note they could not take into account factors that might have influenced the patients' care before they entered the clinical trials. And their analysis did not include socioeconomic factors because that information was not available for patients. However, they doubt socioeconomic factors could fully explain differences in survival rate because Hispanic and African-American women have similar socioeconomic status in M. D. Anderson's patient referral area.
"We interpret these data as suggesting that intrinsic biological differences in the disease and response to treatment among racial groups contributed to the poorer overall survival rates seen in the African-American cohorts," the researchers conclude.
"It's important to note that African-Americans, and people in all self-reported racial groups, are genetically and culturally diverse," Woodward says. "Not all African-American women will have worse survival prospects for breast cancer, but there are probably subsets of patients for whom we could be doing something better.
"The tools and technology are emerging that will allow us to understand how one person's tumors differ from another and how we can more effectively assign people to treatments," Woodward says.
The paper notes that explaining the association of African-American race with more aggressive breast cancer will be challenging, and suggests analysis of genetic variation and regulation of genes by environmental factors as two potential areas of research.
Co-authors with Woodward, all from M. D. Anderson, are: Eugene Huang, M.D., Marsha McNeese, M.D., George Perkins, M.D., Eric Strom, M.D., and senior author Thomas Buchholz, M.D., all of the Department of Radiation Oncology; Susan Tucker, M.D., Department of Biostatistics; Lavinia Middleton, M.D., Department of Pathology; and Karen Hahn, M.D., and Gabriel Hortobagyi, M.D., Department of Breast Medical Oncology.
Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center
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