International collaborative efforts will help us build the complicated infrastructure needed to develop future clinical trials in rare diseases such as male breast cancer.
—Larissa A. Korde, MD, MPH
Male breast cancer is an uncommon disease, although the incidence has increased over the past couple of decades. As with many other “orphan” diseases, male breast cancer is understudied, especially in randomized controlled trials. Although it shares similarities with female breast cancer, some important differences have emerged. To shed light on this intriguing clinical challenge, The ASCO Post recently spoke with male breast cancer researcher Larissa A. Korde, MD, MPH, Associate Professor, Department of Medicine, Division of Oncology, University of Washington, Seattle.
Training at NCI
Please tell the readers a bit about your background and current work.
I am a medical oncologist by training and specialize in breast cancer. I did my residency at Georgetown University Hospital Center and my fellowship at the National Cancer Institute (NCI), which is where I developed my interest in breast cancer. At the NCI, I worked in the Clinical Genetics Branch in the Division of Cancer Epidemiology and Genetics, where I did research on familial cancer syndromes. And that is where my interest in male breast cancer really accelerated.
International Research Collaboration
Please describe your current research activities.
While at the NCI, I received funding to organize a workshop on male breast cancer, bringing together male breast cancer researchers from all over the world. We had a series of comprehensive discussions about the state of the science and what needed to be done as we moved forward. In part, the workshop helped with an ongoing parallel effort in which a consortium was being formed to engage in highly coordinated research in male breast cancer. The European consortium is led by Fatima Cardoso, MD, and the American side is led by Sharon Giordano, MD, from MD Anderson Cancer Center.
The result of this collaboration is a large study in three parts with a retrospective component that has already been presented at the ASCO Annual Meeting.1 The second component is an ongoing prospective study, which will eventually lead to the third arm, a clinical trial in male breast cancer.
One goal of the prospective element is to bring together a variety of researchers interested in male breast cancer and examine the current and potential interventions in this disease, rather than just extrapolate from the work in female breast cancer.
Naturally, one of the difficulties in studying a rare disease such as male breast cancer is accruing enough patients to power a trial. However, by collaborating with a group of physicians, even if each researcher can only provide eight or ten patients, when you have an international collaboration that aggregates all the small groups into one, it gives you enough patients to power the study.
Clinical Trials Model
Clinical trial accrual in the major cancers is a formidable challenge. How do you approach accrual in a rare disease such as male breast cancer?
In the past, the data on male breast cancer have been gathered retrospectively. If one site sees only five or six cases a year, developing a trial becomes very difficult. In fact, about 5 years ago, the Southwest Oncology Group endeavored to perform a prospective clinical trial in male breast cancer but failed to do so due to poor accrual. That is why we are hopeful that the three-step collaborative process might provide a model for clinical trials in rare malignancies such as male breast cancer.
There are several sites across the country and the world that see a larger-than-normal number of cases of male breast cancer, so getting a cooperative atmosphere with these sites will help move the clinical trial process ahead. For instance, MD Anderson Cancer Center has a very large population of patients with male breast cancer, as does Memorial Sloan Kettering Cancer Center. Identifying these centers with high male breast cancer populations in the United States as well as those in Europe has put some big numbers on the disease, which has given us some strong conclusions about its pathology and biology.
Searching for Genetic Clues
Have genetic risk factors for male breast cancer been identified?
Although breast cancer is fairly uncommon in men, we know that the development of this disease in men is associated with BRCA2 gene mutations. The work on other risk factors has been through retrospective epidemiologic studies. I think the genetic component will come along, because during the current international multi-institutional studies, DNA will be collected, and that will allow for multigene sequencing, which has not previously been done on a large scale for male breast cancer.
And we are very interested in determining whether there are mutations in genes other than BRCA2 that predispose men to breast cancer. There are some clues gathered from the retrospective studies that have been done, but nothing concrete has been discovered. Emerging data suggest that there are several notable differences between male and female breast cancer, including a higher rate of hormone positivity, lower HER2 positivity, and more advanced disease at the time of diagnosis.
Have any studies showed a risk factor for men with higher hormone levels?
Not that I know of. However, we do know that men with gynecomastia have an increased risk of male breast cancer, which may be reflective of estrogen exposure.
BRCA Mutation Testing
How has identifying BRCA2 as a risk factor for male breast cancer affected clinical practice?
Clinical practice guidelines currently recommend BRCA mutation testing for all men who are diagnosed with breast cancer. The guidelines take into account personal cancer history, family history, age at cancer diagnosis, ethnicity, and history of risk-reducing surgeries.
Treatments for Men vs Women
Please discuss the current treatment options in male breast cancer.
For the most part, we extrapolate treatments from what we see in female breast cancer. We use a variety of chemotherapies in more aggressive disease, and the mainstay for earlier-stage disease would be hormone therapy with tamoxifen.
Perhaps one of the big differences in treating male breast cancer vs female breast cancer is that aromatase inhibitors are commonly prescribed for postmenopausal women. However, in men, we do not have enough data to be sure how aromatase inhibitors will work in male breast cancer. In fact, there may be some biologic reasons why aromatase inhibitors do not work in male breast cancer, and that is an important area that needs more study. Therefore, it is essential to get the message out to community practitioners that tamoxifen is the standard of care for male breast cancer, and aromatase inhibitors should only be used in combination with a gonadotropin-releasing hormone agonist.
Do you have any final comments on male breast cancer?
The current international Male Breast Cancer Coalition will help us make great strides in understanding the unique biology, genetics, and optimal treatment for men with breast cancer. Equally important, international collaborative efforts will help us build the complicated infrastructure needed to develop future clinical trials in rare diseases such as male breast cancer. Our consortium has multiple sites across the country, all of which will gather crucial data that will ultimately translate into better care for our patients, so stay tuned. ■
Disclosure: Dr. Korde reported no potential conflicts of interest.
1. Korde LA, Zujewski JA, Kamin L, et al: Multidisciplinary meeting on male breast cancer: Summary and research recommendations. J Clin Oncol 28:2114-2122, 2010.