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Breast Cancer in Men
William B. Ershler, MD
Breast cancer occurs in approximately 1 in 100,000 men each year,1 a rate that is slightly less than 1% of that in women. Although the rate might be rising somewhat,1-3 the absolute number of cases remains low (less than 2000 new cases per year in the United States).1 Although the majority of patients will have no discernible risk factor, breast cancer is more common in men who have a family history of breast cancer, who have sustained a bone fracture after the age of 45 years old, and who are obese.4 In a meta-analysis,5 men with the following characteristics also were found to be at increased risk: never married, Jewish ancestry, gynecomastia, history of testicular or liver disease, or prior chest wall irradiation. Much of those with a family history of breast cancer can be attributed to inherited mutations in BRCA (both 1 and 2) and, as with women, those who carry these mutations are likely to be diagnosed in their 30s and 40s.6,7
Male breast cancer has certain histologic and biochemical features that are different from breast cancer in females. An overwhelming majority exhibit invasive ductal histology (approximately 90%), whereas lobular histology is rare.8-10 Almost 90% will express estrogen receptor and 80% progesterone receptor,2,8 whereas Her2 overexpression occurs about half as frequently as in females (approximately 10%).11,12
Typically, male breast cancer will present as a small subareolar painless mass with nipple involvement in 40%-50% of cases.13,14 In contrast, gynecomastia is more often bilateral, less well defined, and tender. Mammography also is helpful in distinguishing gynecomastia from tumor, but any suspicious mass should be biopsied. As with breast cancer in women, staging involves assessment of tumor size, axillary node involvement, and presence of distant metastases. Surgical approach also is similar, with the modified radical mastectomy and axillary node dissection the most commonly undertaken procedure. A negative sentinel lymph node biopsy precludes the necessity for axillary node dissection unless there is clinical suspicion of involvement based on either physical exam or imaging studies.
Evidence on which to balance therapeutic options is not available for male breast cancer and, thus, decisions are most often extrapolated from data derived from clinical trials that define management stage-matched female breast cancer. Because the majority of cases are hormone-receptor positive, adjuvant tamoxifen is widely prescribed, and retrospective analyses would suggest this provides survival advantage.2,15 Similarly, there is very little data on which to base the use of adjuvant chemotherapy for breast cancer in men. Thus, under circumstances in which chemotherapy would be recommended for female breast cancer, similar recommendations are typically offered to men.
The SEER database was recently examined by Harlan and colleagues to define clinical features and survival in 512 male breast cancer patients diagnosed in 2003 and 2004.14 They found that among men who had invasive disease, 86% underwent mastectomy, 37% received chemotherapy, and 58% received hormone therapy. In multivariate analysis, tumor size (p = .01) and positive lymph node status (p < .0001) were associated positively with the use of chemotherapy, whereas age group (p < .0001) and current unmarried status (p = .01) had negative associations. As would be expected, factors associated with poor prognosis were associated with the selection of chemotherapy.
Thus, there remain numerous questions regarding male breast cancer. These include a finer definition of risk factors and a more thorough understanding of the biological differences that exist when cancer develops in the male breast. It is unlikely that we will see randomized clinical trials to distinguish an optimal therapeutic approach, but hopefully, with a better understanding of the genetic and molecular antecedents, specific targeted therapy will become available. In the meantime, male breast cancer treatment decisions will require abstraction from the experiences in women with the disease.
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13. Goss PE, et al. Male breast carcinoma: a review of 229 patients who presented to the Princess Margaret Hospital during 40 years: 1955-1996. Cancer. 1999;85:629-639.
14. Harlan LC, et al. Breast cancer in men in the United States: a population-based study of diagnosis, treatment, and survival. Cancer. 2010;116:3558-3568.
15. Ribeiro G, Swindell R. Adjuvant tamoxifen for male breast cancer (MBC). Br J Cancer. 1992;65:252-254.