October 30, 2006, 5:56 PM CT

Oral Contraceptives Increase Risk For Breast Cancer

A meta-analysis published in the recent issue of Mayo Clinic Proceedings indicts oral contraceptives as putting premenopausal women at significantly increased risk for breast cancer, especially women who use them prior to having a child.

The meta-analysis builds on many studies with similar findings. But even as the findings stack up, many women are unaware of the risks posed by oral contraceptive use prior to pregnancy, says lead study author Chris Kahlenborn, M.D., of Altoona Hospital in Altoona, Pa.

Dr. Kahlenborn says the discrepancy between risk and patient awareness prompted the meta-analysis, which involved extracting data from 34 studies on whether oral contraceptive (OC) use is associated with premenopausal breast cancer. Included in the studies were women who were premenopausal or younger than 50 and who had been, in most cases, diagnosed with breast cancer during or after 1980.

"As I studied the medical literature, I noticed that a trend appeared," says Dr. Kahlenborn. "Namely, OC use prior to first-term pregnancy seemed to consistently increase the risk of premenopausal breast cancer. Although the trend was apparent, premenopausal women have continued to hear that OCs are basically safe".

Rather, patients should know that sustained oral contraceptive use prior to pregnancy increases a premenopausal woman's risk of developing breast cancer, saysDr. Kahlenborn. He says physicians should better inform their patients of the risks associated with oral contraceptives and calls it a "clear-cut informed consent issue".........

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October 30, 2006, 5:34 PM CT

How Multiple Copies Of A Gene Affect Metastasis?

Researchers at UT Southwestern Medical Center have for the first time described how multiple copies of a gene are responsible for metastases in early-stage breast cancer and poor prognosis for patients.

According to a research findings published in this week's issue of the Proceedings of the National Academy of Sciences, the gene, called uPAR, offers a promising target for therapeutic drugs to stop or slow the progression of the disease and could serve as a screening tool for assessing which types of drugs a patient will respond to.

The gene launches a biochemical process in which a molecule called plasmin perforates the membranes of tissues, causing the membranes to break down and allowing the cancer cells to escape into the bloodstream and to adjacent tissues. The result is metastasizing breast cancer. About 20 percent to 25 percent of breast-cancer patients were shown to have uPAR gene amplification, which means they carry too many copies of the gene.

"The uPAR system probably plays a role in metastases in many of the common solid tumors," said Dr. Jonathan Uhr, professor in the Cancer Immunobiology Center and of microbiology and the study's senior author.

While analyzing slides of individual tumor cells - either from the primary tumor or circulating tumor cells - of 72 patients with advanced recurrent breast carcinoma, the UT Southwestern research team discovered how uPAR may work in concert with another known breast cancer gene, HER-2.........

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October 27, 2006, 5:15 AM CT

linking ethnic identity to breast cancer genes

Genetic research over the past decade has linked Ashkenazi Jewish ethnicity to an increased risk for hereditary breast cancer, so much so that certain gene mutations have become known as "Jewish ancestral mutations." But a new study released in the recent issue of The American Journal of Public Health challenges this approach, warning that disparities in access to care and other unintended consequences can, and have, resulted.

The study, by Columbia University College of Physicians & Surgeons researchers, notes that while three recognized breast cancer mutations are present in 2-3 percent of the Ashkenazi Jewish population, similar prevalence studies have not been carried out in other ethnic groups. In addition, the study finds that research linking the breast cancer mutations with Ashkenazi Jews has been beset by methodological problems that cast doubt on the use of ethnicity as the basis for genetic research on disease.

"The linking of Ashkenazi Jews to a deadly disease raises serious scientific and social concerns," said co-author Sheila M. Rothman, PhD, Professor of Sociomedical Sciences at the Center for the Study of Society and Medicine. "Focusing genetic studies on a specific ethnic group confers disadvantages to that group and others. For Ashkenazi Jews it raises the risk of stigmatization and insurance or job discrimination. For other groups, it introduces a gap in access to testing and treatment".........

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October 27, 2006, 5:08 AM CT

Videoconferencing In Pediatric Oncology

An article in the January 2007 issue of the Pediatric Blood & Cancer examines the use of videoconferencing between industrialized and developing countries as a way of improving patient care. The journal is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/pbc.

Pediatric oncology has seen vast improvements in survival rates in industrialized countries over the last several decades, but developing nations are still lagging behind, despite the fact that up to 85 percent of childhood malignancies occur in these countries. Obstacles to advances in the development of pediatric oncology programs include poverty, malnutrition, lack of education, and compliance. Additional factors are a shortage of pediatric oncologist specialists, a lack of cross communication between different disciplines, which leads to delayed and improper referrals, and the tendency to seek multiple second opinions due to a distrust of the quality of available medical care.

Efforts to improve medical care in developing countries include twinning programs that involve the exchange of personnel between participating institutions, a practice that is time consuming and expensive. Telemedicine, another way of communicating and distributing information, is already being used in industrialized countries for educational purposes, second opinions and quality assurance in a number of fields, but there are few reports of its impact in developing countries.........

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October 22, 2006, 11:23 PM CT

Choosing Chemotherapy Using Genomics

Scientists at Duke University's Institute for Genome Sciences & Policy have developed a panel of genomic tests that analyzes the unique molecular traits of a cancerous tumor and determines which chemotherapy will most aggressively attack that patient's cancer.

In experiments reported in the November 2006 issue of the journal Nature Medicine, the researchers applied the genomic tests to cells derived from tumors of cancer patients. They found that the tests were 80 percent accurate in predicting which drugs would be most effective in killing the tumor.

The Duke team plans to begin a clinical trial of the genomic tests in breast cancer patients next year.

The new tests have the potential to save lives and reduce patients' exposure to the toxic side effects of chemotherapy, said Anil Potti, M.D., the study's lead investigator and an assistant professor of medicine in the Duke Institute for Genome Sciences & Policy. The tests are designed to help doctors select and initiate treatment with the best drug for a patient's tumor instead of trying various drugs in succession until the right one is found, Potti said.

"Over 400,000 patients in the United States are treated with chemotherapy each year, without a firm basis for which drug they receive," said Joseph Nevins, Ph.D., the study's senior investigator and a professor of genetics at the Duke Institute for Genome Sciences & Policy. "We believe these genomic tests have the potential to revolutionize cancer care by identifying the right drug for each individual patient".........

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October 19, 2006, 9:25 PM CT

Protein That Helps Chickenpox Spread

A team of researchers at the National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health (NIH), has identified a human protein that helps varicella-zoster virus, the cause of chickenpox and shingles, spread from cell to cell within the body.

NIAID virologist Jeffrey I. Cohen, M.D., and NIAID research fellow Qingxue Li, M.D., Ph.D., discovered that a surface protein of varicella-zoster virus attaches to a cellular protein called insulin-degrading enzyme, using it as a receptor to enter and infect cells. In the October 20, 2006 issue of the journal Cell, they also describe how interfering with this interaction inhibits the spread of virus among cells in the test tube. The discovery of this receptor is important in understanding varicella-zoster virus, say Drs. Cohen and Li.

Their finding is also an important first step towards designing new therapies for shingles. "If safe and effective ways of disrupting this interaction can be found, eventually new interventions may be developed for treating people with this painful and debilitating disease," says NIAID Director Anthony S. Fauci, M.D.

Shingles occurs only in people who have already had chickenpox. Once chickenpox has run its course, some virus remains dormant in nerve cells at the base of the brain and alongside the spinal cord. With advancing age and diminished immunity, the virus can reactivate years later and travel down the nerve cells to the skin. There it multiplies, causing the blistering rash of shingles and damaging sensory nerve endings. The rash commonly heals within a few weeks, but the nerve damage sometimes causes one of the worst complications of shingles--a severe type of pain called postherpetic neuralgia, which can last for months or even years.........

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October 19, 2006, 8:47 PM CT

Targeted Tumor Therapy

Targeted tumor therapy lobs toxic payloads directly into tumors to destroy cancer cells while leaving normal cells unharmed. In the case of radiotherapy, these missiles, which should unerringly home in on the target and make it implode, consist of radioactive bullets guided by small molecules--known as agonists--that recognize and then activate specific receptors over-expressed on the surface of tumor cells.

But a team including researchers at the Salk Institute for Biological Studies and collaborators in Switzerland now shows that it may be better to exploit small molecules that antagonize rather than activate receptors. Those findings appear in this week's Early Online Edition of the Proceedings of the National Academy of Sciences.

"Our findings mark a paradigm shift," says Jean Rivier, a professor in the Clayton Foundation Laboratories for Peptide Biology at the Salk. "In the past, radiolabeled antagonists were never considered for targeted cancer therapy since they don't trigger the internalization of the receptor/ligand complex, which was thought to be the critical step towards accumulation of the payload. But we found that antagonists have other properties that may considerably improve the sensitivity of diagnostic procedures and improve the efficacy of receptor-mediated radiotherapy," he adds.........

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October 18, 2006, 10:39 PM CT

Cancer Stem Cells Linked To Radiation Resistance

Certain types of brain cancer cells, called cancer stem cells, help brain tumors to buffer themselves against radiation treatment by activating a "repair switch" that enables them to continue to grow unchecked, researchers at Duke University Medical Center have found.

The researchers also identified a method that appears to block the cells' ability to activate the repair switch following radiation treatment. This finding may lead to the development of therapies for overcoming radiation resistance in brain cancer as well as other types of cancer, the researchers said.

Working with animal and cell culture models, the researchers found that a specific cellular process called the "DNA damage checkpoint response" appears to enable cancer stem cells to survive exposure to radiation and to switch on a signal to automatically repair any damage caused to their DNA.

"In recent years, people have hypothesized that cancer stem cells are responsible for the resistance of malignant tumors to radiation treatment," said Jeremy Rich, M.D., senior investigator of the study and an associate professor of neurology at Duke. "We have shown, for the first time, that this is indeed the case".

The findings appear Oct. 18, 2006, in the advance online edition of the journal Nature. The research was supported by the National Institutes of Health and a number of philanthropic organizations [complete list below].........

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October 17, 2006, 9:55 PM CT

Femara More Effective Than Nolvadex

Researchers affiliated with the BIG-98 trial comparing Femara® (letrozole) to Nolvadex® (tamoxifen) have reported that longer follow-up confirms the superiority of Femara in postmenopausal women with early, hormone-positive breast cancer. The details of this follow-up study were presented at the 2006 annual European Society for Medical Oncology (ESMO) meeting in Istanbul in October.

Femara is an aromatase agent that is approved for first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced breast cancer; metastatic breast cancer; advanced breast cancer in postmenopausal women with disease progression following anti-estrogen therapy; and as neo-adjuvant therapy. It is also approved for extended adjuvant therapy in early breast cancer, following 5 years of treatment with Nolvadex, based on phase III clinical trial results. Several clinical trials are ongoing to help elucidate optimal timing and/or sequencing of aromatase agents and Nolvadex in the treatment of hormone-positive women with breast cancer in the adjuvant setting, and it appears that aromatase agents are providing superior results to those of Nolvadex in several settings in the treatment of hormone-positive breast cancer.........

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October 17, 2006, 9:46 PM CT

Ethnic Variations In Hormone Levels And Breast Cancer

Researchers have known that a woman's natural hormone levels can affect her risk of developing breast cancer. A new study from the University of Southern California (USC) has found that the natural levels of estrogens in post-menopausal women varies by ethnicity and race, and may explain the differences in the groups' breast cancer rates. The study appears in the recent issue of Cancer Epidemiology, Biomarkers & Prevention.

Using data from the Multiethnic Cohort Study, V. Wendy Setiawan, Ph.D., assistant professor of preventive medicine at the Keck School of Medicine of USC, and her colleagues determined that of the five primary ethnicities/races in the cohort, native Hawaiians have the highest risk of breast cancer--65 percent greater than whites. They also had some of the highest levels of circulating estrogens.

"We had observed that some groups, such as native Hawaiians have higher breast cancer rates compared to white women. We knew hormones are a factor, so we decided to test them," says Setiawan. "The research seems to support that idea".

The researchers also found that Japanese-American women have comparatively high estrogen levels and the second highest breast cancer risk of the five groups. "This is interesting because breast cancer rates have been increasing steadily in Japanese women who live in the United States, as well as in women who live in Japan," Setiawan says. "We think it could be caused by lifestyle changes that impact age at first menstruation or other factors".........

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