Cancer - December 2012 Archives

Melanoma is an often deadly skin cancer.  In this episode of Medical Edge Radio, Mayo Clinic Dr. Svetomir Markovic tells us, melanoma can show up ...

A new study confirms that a patient’s ability to metabolize the breast cancer drug tamoxifen affects the outcome of her treatment. Researchers at the Mayo ...

ROCHESTER, Minn. — For nearly a decade, breast cancer researchers studying the hormone therapy tamoxifen have been divided as to whether genetic differences in a liver enzyme affect the drug's effectiveness and the likelihood breast cancer will recur. A new study by researchers from the Mayo Clinic Cancer Center and the Austrian Breast and Colorectal Cancer Study Group provides evidence that genetic differences in the enzyme CYP2D6 play a key role in how well tamoxifen works. MULTIMEDIA ALERT: Video of Dr. Goetz is available on the Mayo Clinic News Network. "Our findings confirm that, in early breast cancer treated with tamoxifen, genetic alterations in CYP2D6 lead to a higher likelihood of recurrence and death," says Mayo Clinic oncologist Matthew Goetz, M.D., lead author of the study in the journal Clinical Cancer Research. In the clinical trial, Dr. Goetz and his colleagues studied the rates of cancer recurrence and death in two groups: postmenopausal women with primary estrogen receptor-positive breast cancer who received tamoxifen for five years and those who received tamoxifen for two years followed by the aromatase inhibitor anastrozole for three years. Anastrozole is a breast cancer drug whose metabolism does not require the CYP2D6 enzyme. The study showed that women who were born with genetic alterations of CYP2D6 that abolish the enzyme's critical metabolizing activity and who took tamoxifen for five years had recurrence of breast cancer, or died at a rate 2.5 times higher than women with normal CYP2D6 enzyme activity. Women with intermediate levels of the CYP2D6 enzyme had rates of recurrence or death 1.7 times higher than women with normal CYP2D6 activity. Importantly, Dr. Goetz notes, that genetic alterations in CYP2D6 did not affect the likelihood of recurrence or death in women who switched to anastrozole after two years of tamoxifen. "Switching from tamoxifen to an aromatase inhibitor may be one reason for the discrepant studies surrounding CYP2D6 and tamoxifen — as information about whether a patient took an aromatase inhibitor after tamoxifen was not available in most of the prior studies," says senior author James Ingle, M.D., of Mayo Clinic, an expert on hormone therapies for breast cancer. A blood test can determine whether a woman has alterations in CYP2D6 and predict how efficiently her body will convert tamoxifen to endoxifen. Approximately 5 to 7 percent of European and North American populations are considered poor metabolizers of tamoxifen. "The results of this successful high-level international research collaboration are an important step forward in our quest to individualize breast cancer treatment and provide tailored care to women with breast cancer," says Michael Gnant, M.D., professor of surgery at the Medical University of Vienna and president of the Austrian study group. So what should a woman do if she is unable to effectively metabolize tamoxifen into its most active form? Dr. Goetz believes that the current recommendation of switching from tamoxifen to an aromatase inhibitor is likely to result in the greatest benefit in women with decreased CYP2D6 metabolism. For CYP2D6 poor metabolizers, avoiding tamoxifen altogether and starting out with an aromatase inhibitor may be the best approach, he says. Dr. Goetz's group is working with the National Cancer Institute to develop endoxifen as an alternative to tamoxifen. If women can be given endoxifen, the active part of tamoxifen, it won't matter how tamoxifen gets metabolized, he says. The study is partially funded by the National Institutes of Health, co-authors include Vera Suman, Ph.D.; Tanya Hoskin; Mary Kuffel; Stephanie Safgren; Carol Reynolds, M.D.; Matthew Ames, Ph.D.; and Richard Weinshilboum, M.D., all of Mayo Clinic; Martin Filipits, Ph.D.; Raimund Jakesz and Margaretha Rudas of the Medical University of Vienna; Richard Greil and Otto Dietze of Paracelsus Medical University, Salzburg, Austria; and Alois Lange and Felix Offner of Medical Hospital Feldkirch, Austria.

"ALL WOMEN HAVE A 1-IN-8 CHANCE OF GETTING BREAST CANCER."  Find out the ...

Many people who have been through cancer and its treatment have trouble with their recovery because of severe, debilitating fatigue that can last for months ...

ROCHESTER, Minn. — Many people who have been through cancer and its treatment have trouble with their recovery because of severe, debilitating fatigue that can last for months or even years. But even though a variety of treatments exist for cancer-related fatigue, few doctors are recommending them to patients, according to a recent Mayo Clinic study appearing in Supportive Care in Cancer. MULTIMEDIA ALERT: Video of Dr. Cheville is available on the Mayo Clinic News Network. The study found few of the available treatment strategies are being offered or prescribed by doctors. Regular physical activity, such as walking with a pedometer, has been shown to ease fatigue. Learning stress reduction and coping techniques can help patients alter daily habits and increase restfulness. However, only one-tenth of patients said their oncology teams instructed them to become more active or try other non-medication-related fatigue-reducing measures. More than 35 percent of patients had been offered sleep-enhancing medication, even though drugs have been shown to be the least effective approach. "Fatigue is a factor that not only significantly diminishes quality of life but is also associated with reduced survival," says study author Andrea Cheville, M.D., a physiatrist with the Mayo Clinic Department of Physical Medicine and Rehabilitation. "Our results suggest that cancer patients are not receiving appropriate treatment for a significant and widespread problem." Researchers queried 160 stage IV cancer patients, men and women, who had moderate to severe fatigue (greater than five on an 11-point scale). Participants with lung, breast, colon or prostate cancer were asked whether their oncology teams had mentioned any of the cancer-fatigue treatments recommended by the National Comprehensive Cancer Network guidelines, such as increasing exercise, seeking psychosocial and behavioral help, and medications. Patients were asked about the extent of the information they had received, whether physicians had provided specific counseling, instructions and recommendations or a prescription to address fatigue. While age and gender were not factors in whether patients received treatment for fatigue, their type of cancer was. Only 15 percent of patients with colon cancer and 17 percent with prostate cancer had their fatigue addressed; 48 percent of breast cancer patients had been advised of psychosocial interventions. When researchers asked about patients' habits at home, they found significant room for improvement. "We found the vast majority of patients were not engaging in behavioral practices that could reduce fatigue and potentially enhance quality of life," Dr. Cheville says. "And almost a third reported napping during the day, which can actually worsen fatigue." For Dr. Cheville, whose research focuses on improving the delivery of supportive care to patients, the study provides a wake-up call.

JACKSONVILLE, Fla. — Researchers at Mayo Clinic's campus in Florida have identified an enzyme specifically linked to aggressive prostate cancer, and have also developed a compound that inhibits the ability of this molecule to promote the metastatic spread of the cancer. Their study, published in the Dec. 18 online edition of Molecular Cancer Research, is the first to link the enzyme PRSS3 to prostate cancer. "This molecule is a protease, which means it digests other molecules. Our data suggests PRSS3 activity changes the environment around prostate cancer cells — perhaps by freeing them from surrounding tissue — to promote malignancy and invasiveness," says the study's senior investigator, Evette Radisky, Ph.D., a cancer biologist in the Mayo Clinic Cancer Center. "I don't think PRSS3 is the only factor involved in driving aggressive prostate cancer, but it may be significant for a certain subset of this cancer — the kind that is potentially lethal," she says. Dr. Radisky and five colleagues at Mayo Clinic in Florida made the discovery by investigating publicly available databases, derived from clinical studies, which contain data on molecules that are upregulated — irregularly switched on — in cancer. They had previously discovered a link between the protease and the earlier stages of breast cancer. The research team wanted to see if any other cancer abnormally expresses this protease, and at what stages so they mined multiple databases. "The link between PRSS3 activity and aggressive prostate cancer jumped out at us," Dr. Radisky says. "We found a definitive trend of increasing PRSS3 expression with cancer progression." Then, in mice models of prostate cancer, the researchers demonstrated that expression of the protease was critical for prostate cancer metastasis. Cancer did not spread in mice in which PRSS3 was silenced. The group had earlier crystallized the structure of the PRSS3 protease, and discovered a place on the enzyme where a small protein therapeutic could bind to plug up the "scissoring" action of the molecule. "The protease has an active site that breaks down other proteins, and our inhibiting agent sticks to the site, shutting it down," Dr. Radisky says. The researchers say their finding suggests several possible future clinical applications.

JACKSONVILLE, Fla. — A research team led by scientists at Mayo Clinic in Florida have decoded the entire pathway that regulates leakiness of blood vessels — a condition that promotes a wide number of disorders, such as heart disease, cancer growth and spread, inflammation and respiratory distress. They say their findings, published online Dec. 17 in the Journal of Cell Biology, suggest that several agents already being tested for other conditions might reverse vessel leakiness. "Now that we understand a lot more about the pathway that leads to leaky blood vessels, we can begin to try to target it in an efficient way, and that is very exciting," says the study's lead investigator, Panos Z. Anastasiadis, Ph.D., chair of the Department of Cancer Biology at Mayo Clinic in Florida. Physicians have attempted to regulate that pathway in cancer through use of VEGF inhibitors, such as Bevacizumab, but these drugs are not as effective as they might be if other parts of the pathway were also inhibited, Dr. Anastasiadis says. The research team, led by Dr. Anastasiadis and Arie Horowitz, Ph.D., at Cleveland Clinic Foundation, found that VEGF is one of two different molecules that affect a key downstream protein, Syx, to regulate the permeability of blood vessels. Blood vessels are made up of endothelial cells that have to fit tightly together to form a solid tubular structure that blood can flow through. The researchers discovered that VEGF turns off Syx, which normally ensures the junctions between endothelial cells are strong. Without Syx, adhesion between the cells is loose, and the blood vessels are leaky. When new blood vessels are needed — such as to feed a growing tumor — VEGF loosens up endothelial cells so new vessels can sprout. Then, after new vessels are formed, a second molecule, angiopoietin-1 (Ang1) works to glue the cells back together, Dr. Anastasiadis says. "These molecules have opposing, yin and yang effects. VEGF kicks Syx out of the junctions between cells, promoting leakiness, and Ang1 brings it back in to stabilize the vessel," he says. The issue in cancer, however, is that VEGF overwhelms the system. "There isn't enough Ang1 to glue the vessels back together, and this leakiness allows cancer cells to escape the tumor and travel to other parts of the body," Dr. Anastasiadis says. "In late stages of the cancer, it also promotes the leaking of liquids into organs, such as the lungs. This results in profound effects that are often lethal." Other disorders, such as inflammation and sepsis, a deadly bacterial infection that can result from excess liquid in lungs, are also induced by a leaky vascular system, he says.

It's known that exercise can reduce cancer-related fatigue, improve sleep, boost a sense of wellness and reduce the recurrence of certain types of tumors. Now, ...

SAN ANTONIO, Texas — Adding the drug trastuzumab to chemotherapy prevents cancer recurrence and improves survival in a large number of women with early stage HER2-positive breast cancer. But trastuzumab does not stop tumors from returning in about 25 percent of patients — and oncologists haven't been able to identify these women before treatment. This situation may soon change, according to a Mayo Clinic study being presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium. VIDEO ALERT: Video of Dr. Perez is available on the Mayo Clinic News Network. A team of U.S. researchers, led by oncologists at Mayo Clinic's campus in Florida, have discovered 27 genes that are significantly associated with a good outcome with concurrent use of trastuzumab and chemotherapy, as well as five other genes linked to a poor outcome using the same treatment regimen. Results of their study — believed to be the first to use gene expression profiling to predict outcome to trastuzumab as part of adjuvant breast cancer therapy — offer a number of future potential benefits, says Edith Perez, M.D., deputy director at large of the Mayo Clinic Comprehensive Cancer Center and director of the Breast Cancer Translational Genomics Program at Mayo Clinic. "These findings also are getting us closer to unraveling the biological factors that are relevant to patient outcome, which will help us improve clinical care," Dr. Perez says. For example, the discovery may help scientists devise a genetic test that can help oncologists select the best treatment for their HER2-positive patients, she says. Further analysis will illuminate the inner biological workings of individual HER2-positive tumors, which could provide clues for novel treatments, Dr. Perez adds. The researchers have already found that the genes linked to outcome can be grouped into different categories that affect tumor functioning, such as cell cycle, cell death, cell receptor signaling, and gene transcription. Dr. Perez and her team plan to validate their findings through collaborations with researchers in the United States and Europe who have led other trastuzumab clinical studies.

Most patients whose breast cancer has spread to their lymph nodes have most of the lymph nodes in their armpit area removed after chemotherapy to ...

Adding the drug trastuzumab to chemotherapy prevents cancer recurrence and improves survival in a majority of women with early stage HER2-positive breast cancer. But trastuzumab ...