Male breast cancers: Finding clues from controversies and insufficient data

Abstract

Male breast cancer is a rare disease, occurring in about 1% of all breast cancers. Can we learn from this uncommon illness? The answer should be a resounding yes, but we are far from understanding the whole story. This issue of the Asia–Pacific Journal of Clinical Oncology features a comprehensive review on male breast cancer by Field et al.1 We learn that the incidence of breast cancer in men may be increasing with elusive etiologies. We also learn that the prognosis is the same as female breast cancer patients, matching the stage by stage and other prognostic factors. However, we are told that 90% or more male breast cancers have positive estrogen receptors and very few (1–2%) have HER-2/NEU gene amplification expression. Therefore, common sense would have suggested that male breast cancer sufferers should have better prognosis than their female counterparts. But that is not the case by literature review. What are the possible explanations? The following speculations may shed some clues for future research: The proliferative drive or signal transduction pathway in male breast cancer may be quite different in that they may have shorter duration of response or early development of drug resistance. However, we do not have any clinical or laboratory evidence to substantiate this notion. Male patients may have more difficulties to accept the diagnosis of a female disease. Hence, they are more prone to be lost for follow-up or stop treatment early. That is, they may not get treated as vigorously as female patients. Again, we need more epidemiological data to support this idea. Or, the existing data on survival are not reliable as most if not all the data are retrospective. There is hardly any clinical trial on female breast cancers that included male patients. Therefore, a fair comparison is not possible. From their review, we understand that there are substantial differences between male and female breast cancers, such as genetic predisposing factors (BRCA2 mutation is the most common form in men as compared to BRCA1 in female patients), histopathology (much less lobular carcinoma in male than in female), hormonal receptors (male breast cancers have more frequent positive estrogen receptor than female patients) and response to aromatase inhibitor (aromatase inhibitors increase testosterone levels in male not in female and less effective in suppressing estrogen in male volunteers). This review paper also pointed out many missing pieces of information in all aspects of male breast cancer. There are hardly any prospective clinical phase II trials with aromatase inhibitors or chemotherapy agents such as taxanes, gemcitabine, vinorelbine which are commonly used in female breast cancer. Rightly so, the authors cautioned the routine use of aromatase inhibitors in men due to differences in endocrine response between both sexes. We are still lacking the essential genomic data in male breast cancer which may provide clues to explain this phenomenon. Although it is of importance and interest to know all the differences and similarities between male and female breast cancer patients, we need to consider what we can do to utilize this information to elicit clues to solve some of the unknown mysteries and advance our knowledge. Unfortunately, not much can be done by a single institution or study group for the time being. Perhaps, one immediate step to be taken should be to form an international study group. Then, prospective phase II studies may become a reality in the near future, as there are too few cases of male breast cancer in any single institution. In essence, clues may be discovered among controversies and from insufficient data, but it requires confirmation and validation. In this case, we need worldwide concerted efforts to study this rare disease: male breast cancer.