1. Goodwin, Peter M.

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AMSTERDAM, Netherlands-The first big international study of male breast cancer pathology has found important features distinguishing it from the female disease-including histologic grade, mitotic activity, fibrotic focus, and tumor-infiltrating lymphocyte (TIL) concentrations-but has revealed the urgent need for more data to guide treatment decision-making (Abstract 7).

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Findings from the International Male Breast Cancer Program, led by the European Organization for Research and Treatment of Cancer (EORTC) in Europe and the Translational Breast Cancer Research Consortium (TBCRC) in the U.S. (EORTC 10085/TBCRC/BIG/NABG), were reported at the 10th European Breast Cancer Congress by Carolien H. M. van Deurzen, MD, a pathologist specializing in breast cancer at Erasmus University Medical Center in Rotterdam, Netherlands.


Research Details

The study examined tumor samples from 1,203 men with breast cancer who made up part of the largest series of this disease ever collected linked to outcome data: 1,483 patients from 23 centers in nine countries.


"The majority of these male breast cancers were ER- and PR-positive and HER2 negative," she told OT. But several pathologic features that are well-established as prognostic in females-including histologic grade-were not significantly associated with outcome in these male patients she said. "If you look in females, grade is significantly associated with outcome."


We also [found] some non-standard features were associated with outcome," said van Deurzen. Mitotic activity was strongly correlated with overall survival and fibrotic focus and having "a limited amount of TILs" were associated with unfavorable outcome, she said.


She explained that there was inadequate information for male patients because a lack of studies, insufficient funding, and males being excluded from female breast cancer studies. She said the EORTC study was addressing this issue by pooling data from all male patients with breast cancer collect over a period of 20 years from the Breast International Group and the North America Breast Group.

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Co-chair of the International Program, Fatima Cardoso MD, Director of the Breast Unit at Champalimaud Clinical Centre in Lisbon, Portugal, and Chair of the European Breast Cancer Conference, told OT the study had formed its global network to study the biology of male breast cancer because there had until not been any major studies: accounting for only 1 percent of all breast cancer.


She said there had-up until now-been only a few series of studies in male breast cancer with too few patients or clinical cases. "And we treat men as if they were women. And obviously there is a difference: particularly hormonal," she said. She noted breast cancer is linked to the hormonal environment. "So, for sure there are differences that will have clinical implications. And this is what we are doing: finding out those differences," she said.


When she was asked about the clinical implications of pathologic differences, Cardoso suggested the fact that male breast cancer is almost always ER-positive may explain why grade is not a strong prognostic marker in male breast cancer: "And what we do in clinical practice if we have ER-positive grade 3 [is to] give chemotherapy." And she added the EORTC study found that in male patients that may not be appropriate and this now needs confirmation.


Therapy Differences

But Cardoso did have clinical recommendations for managing male breast cancer. "What the physicians and the patients need to know is that not everything done in female breast cancer can be extrapolated," she said.


One practical example she mentioned was about the choice of endocrine therapy. In non-metastatic early breast cancer, the benefit of tamoxifen was proven, she stated. "We do not have a proven value yet for aromatase inhibitors-particularly if given alone," she continued. And she pointed out that AIs can be detrimental: "And so this is a very important message: Don't use an aromatase inhibitor alone in a male patient. What we have is improved survival with tamoxifen. So this is a simple message everyone can know," she said.


And Cardoso held out a beacon of scientific insight for the future, "From this study, what we have understood is that there are differences in biology both in the traditional pathologic factors-particularly grade. And what we are now doing is deep sequencing," she said. She added that understanding the genome of male breast cancer-and comparing it with female cancer was a priority to look for if there are specific treatments. "For example we are studying the androgen receptor that seems to be very important for male breast cancers," she concluded.


David Cameron, MD, MRCP, Professor of Oncology at the University of Edinburgh, U.K., and Clinical Director of the Edinburgh Cancer Research Centre, who was not directly involved in the research, said the study conclusions were important: "It has always been assumed, based on limited information, that men with breast cancer should be treated in the same way as women. For the first time, by studying more than 1,000 cases, it is becoming clear that that this is not so," he emphasized.


Peter M. Goodwin is a contributing editor.