Breast Cancer in Men

As noted by Dr. Buzdar, breast cancer rarely affects men. According to the most recent data from the National Cancer Institute's Surveillance Epidemiology and End Results program and the National Program of Cancer Registries, the incidence of invasive breast cancer is 1.5 cases per 100,000 men vs 134 cases per 100,000 women.[1] Breast cancer in women is a far greater public health problem and understandably has received the lion's share of research funding and public attention. Male breast cancer has been in the headlines recently due to the efforts of former US Senator Edward Brooke, who is attempting to educate the public regarding his own diagnosis at age 83.[2] As Senator Brooke learned, selecting the best treatment approach for a condition commonly believed to afflict women can be quite challenging for a man. In his article, Dr. Buzdar provides an excellent overview of what we have learned about the presentation, biology, and treatment of this uncommon problem. Small Retrospective Studies
Our clinical understanding of breast cancer in men comes largely from single-institution retrospective series, typically involving 50 to 200 patients diagnosed and treated over a period of 20 to 40 years. Not surprisingly, data from these series can be conflicting. Some studies have suggested that male breast cancer is associated with a worse prognosis than female breast cancer, while others have reported contrary findings.[3] Recent series re port 5-year overall survival rates in male breast cancer patients ranging from 50% to 87%.[3-7] In some series, HER2/neu positivity has been nonexistent, while in others, as many as 29% of men have had HER2/neu positive tumors.[8]. Although high percentages of estrogen- receptor (ER)-positive tumors are consistently reported, the immunophenotype of these tumors may differ significantly from tumors in women,[9,10] and it is less clear that ER-positive status conveys the same prognostic implications.[6,11] Differences across these reports can be attributed to small sample sizes, variations in diagnostic technique, and changes in treatment patterns. Larger studies using population-based cancer registries promise to refine some of these estimates and provide a more accurate description of outcomes over time.[11,12] Male vs Female Breast Tumors
It seems clear that breast cancer in men may differ in important ways from the disease in women. Many clinicians and investigators believe that breast cancer in women is not a single disease, but rather, a family of diseases with a widely varying natural history and response to therapy. In the years ahead, the challenge will be to differentiate the tumors types on a molecular level in a reliable and consistent fashion, and to translate this information to the clinical setting. We will soon be able to use molecular techniques to understand the similarities and differences in breast tumors between men and women. At present, the question is whether male breast cancers are sufficiently similar to those in women to allow us to extrapolate findings from clinical trials that excluded men. This question becomes particularly important in the adjuvant setting, where decisions are often guided by diminishingly small but real benefits based on data from large clinical trials. Data from population studies show improvements in outcomes over time coincident with increasing use of adjuvant therapy,[5] but it is difficult to use this information in making treatment decisions for individual patients. Unfortunately, but understandably, no randomized trials and few prospective studies of any kind have focused on men with breast cancer. Breast cancer trials are frequently restricted to women. It has been argued that little would be learned by including men in these trials because their presence would be dwarfed by the large number of female patients. Furthermore, there has been concern that male breast cancer might be sufficiently different from female breast cancer to have an impact on the trial's results. A search of the National Cancer Institute's clinical trial database on the Web revealed that on a given day, approximately 138 phase II and phase III breast cancer treatment trials were open, but only 22 (16%) were open to men. Of 50 phase III trials in breast cancer, only 2 (4%) were open to male patients.[13] Conclusions
If male breast cancer is a sufficiently different condition to warrant exclusion from most breast cancer trials then surely it deserves dedicated trials. The rarity of male breast cancer is such that large cooperative group studies would be required. In fact, clinical trials have been conducted successfully in similarly rare conditions such as mesothelioma and hairy cell leukemia. While small studies may further elucidate the biology of male breast cancer, and larger population database studies may improve our understanding of baseline characteristics and outcomes, only inclusion in large clinical trials or separate co- operative group studies will truly answer the clinical questions. In the absence of these data, it seems reasonable to treat male patients following the same guidelines applied to females, but this practice should be bolstered by data as soon as possible. It is time for the oncology community to decide if what's good for the goose is truly good for the gander.