Matthew Goetz

ROCHESTER, Minn. — Mayo Clinic researchers have identified the drug estradiol as a potential new treatment for a subset of women with triple-negative breast [...]

  ROCHESTER, Minn. – Z-endoxifen, a potent derivative of the drug tamoxifen, could itself be a new treatment for the most common form [...]

ROCHESTER, Minn. — Tumor sequencing is increasingly used to select treatment for patients with cancer, but its role in women with newly diagnosed breast cancer [...]

ROCHESTER, Minn. — Clinical recommendations discouraging the use of CYP2D6 gene testing to guide tamoxifen therapy in breast cancer patients are based on studies with flawed methodology and should be reconsidered, according to the results of a Mayo Clinic study published in the Journal of the National Cancer Institute. https://www.youtube.com/watch?v=c7LzSSnY3Ko Journalists:  Sound bites with Dr. Matthew Goetz are available in the downloads. For years, controversy has surrounded the CYP2D6 gene test for breast cancer. Women with certain inherited genetic deficiencies in the CYP2D6 gene metabolize tamoxifen less efficiently, and thus have lower levels of tamoxifen’s active cancer-fighting metabolite endoxifen. Numerous studies have shown that these women gain less benefit from tamoxifen therapy and have higher rates of recurrence. MEDIA CONTACT:
 Joe Dangor, Mayo Clinic Public Affairs, 507-284-5005, newsbureau@mayo.edu.

ROCHESTER, Minn. — Sept. 26, 2013 — October is National Breast Cancer Awareness Month, and Mayo Clinic breast cancer experts are available to discuss risk factors, screening and treatments. MULTIMEDIA ALERT: Video and audio are available for download on the Mayo Clinic News Network. After skin cancer, breast cancer is the most common cancer diagnosed in women in the United States, with more than 238,000 new diagnoses estimated this year. While breast cancer is predominantly found in women, about 1 percent of all breast cancers are diagnosed in men. As with all cancers, patients should be aware of the importance of prevention and early detection in order to give themselves the best opportunity to be treated if cancer is found.

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.

ROCHESTER, Minn. — April 9, 2012.   The Breast Cancer Genome Guided Therapy Study (BEAUTY Project) will help physicians tailor chemotherapy to breast cancer patients based on their individual genomes and the genomes of their tumors. Mayo Clinic researchers will obtain three whole genome sequences: one from the patients' healthy cells before treatment, and two tumor genomes – one before chemotherapy and one after. Patients will be paired with mouse "avatars" that will help physicians identify the best treatment for each person.

"What is so exciting about this study is that it has the potential to really bring individualized medicine to our patients," says Matthew Goetz, M.D., Mayo oncologist and study co-leader. "It will transform how we conduct breast cancer research and how drug therapies are delivered to women with breast cancer."

In phase one of the BEAUTY Project, researchers will study the first 200 participants to look for common mutations that allow some tumors to adapt and thrive during chemotherapy. This information will help doctors identify new drugs and treatment strategies. Women diagnosed with "high-risk" cancers who are scheduled to receive standard chemotherapy before surgery will have their healthy genome and their breast cancer tumor cells sequenced before treatment, and then receive the commonly prescribed chemotherapy to shrink the tumor. At surgery, the residual cancer tumor cells will be sequenced again to evaluate how they have mutated and adapted to chemotherapy. In addition, patients' tumor tissue will be kept alive by implanting cell lines in immune-compromised mice — before and after chemotherapy. The use of these mouse "avatars'' will let researchers study the effects of chemotherapy on individual patient tumors and identify the best treatment, without risk of harm to the patient. "Patients are pleased after definitive breast surgery to be cancer free," says Judy Boughey, M.D., a Mayo breast surgeon and study co-leader. "Unfortunately, a subset of high-risk patients still may experience recurrence, even months or years later. We designed this study to give those patients hope that our ability to decode the genome of every patient might give us new tools to treat cancer."