Breast Cancer in Men Overview of Male Breast Cancer
The etiology, diagnosis, and treatment of breast cancer in males is similar to that in females. Unlike breast cancer in females, however, breast cancer in men is rare. Although its frequency has increased in recent decades—particularly in the urban United States, Canada, and the United Kingdom—breast cancer in males accounts for less than 1% of breast cancers. In the United States, males are expected to account for only 2600 of the estimated 249,260 cases of breast cancer predicted to occur in 2016.
Unfortunately, this rarity has largely precluded prospective randomized clinical trials. It may also contribute to the infrequency of early diagnosis. Men tend to be diagnosed with breast cancer at an older age than women, and they have proportionately higher mortality, although outcomes for male and female patients with breast cancer are similar when survival is adjusted for age at diagnosis and stage of disease.
Environmental and genetic risk factors for male breast cancer have been identified. Male breast cancers are reported to be associated with the following.
- Marital status (never married at higher risk)
- Previous breast pathology
- History of testicular pathology
- Family history of breast cancer
The family history is positive for breast cancer in approximately 30% of male breast cancer cases. A familial form of breast cancer is seen in which both sexes are at increased risk for breast cancer. Familial cases usually have BRCA2 rather than BRCA1 mutations. Men who inherit BRCA2 have about a 6% lifetime risk of breast cancer, which is 100-fold higher than in men without the mutation. Klinefelter syndrome is the strongest risk factor. Males with the syndrome have a risk of breast cancer that approaches that of females. Exogenous hormone therapy, such as treatment for prostate cancer, is not associated with an increased risk of male breast tumors. No association with smoking history was reported. Meta-analysis of epidemiology of male breast cancer failed to reveal any clear association with other potential risk factors such as reproductive history, education, various diseases, or exposure to drugs. Case-control studies on this subject have been confounded by small numbers or contradictory results.
Overall, male breast cancer shares risk factors associated with female breast cancers, especially high estrogen levels. A few transsexual (male to female) patients have been reported with breast cancer 5-10 years after initiation of estrogen therapy; however, it is not known whether these patients are at increased risk compared with non-transsexual males. Excessive estrogen levels in men may also be related to obesity, liver disease, and thyroid dysfunction. These epidemiologic factors, in addition to studies suggesting that men with breast cancer have elevated estriol production, indicate a relationship between male breast cancer and hormones in addition to the well-established relationship with genetics.
Male breast cancer usually presents as a painless lump. In 75% of cases, the lump is a hard and fixed nodule in the subareolar region, with nipple involvement more common than in women. Often, the disease is not detected until late in its course: more than 40% of patients have stage III or IV disease at diagnosis. Lack of awareness that men develop breast cancer may possibly contribute to diagnosis of breast cancer in men at more advanced stages than in women.
In patients with clinical features completely consistent with gynecomastia, breast cancer may be excluded on clinical grounds, and no further evaluation may be necessary. If findings are equivocal, however, mammography can be useful in diagnosis. See Male Breast Cancer Imaging for further information on this topic.
Fine-needle aspiration biopsy can confirm the diagnosis. Histologically, the majority of breast cancers in men are infiltrating ductal carcinomas, but the entire spectrum of histological variants of breast cancer has been seen. Papillary carcinoma is a distant second in frequency. Lobular carcinoma is uncommon. Most male breast cancers (~80%) are hormone receptor positive, 15% overexpress human epidermal growth factor receptor 2 (HER2), and 4% are triple negative (estrogen receptor, progesterone receptor, and HER2 negative).
Treatment and follow up
Treatment of male breast cancer comprises surgery, radiation therapy, and systemic therapy.
The general principles of surgical management of male breast cancer are similar to those of breast cancer in women. Simple mastectomy remains the usual choice for T1 and T2 breast tumors. Nipple- and skin-sparing mastectomy are common in women, but generally not practiced in male breast cancer. Cosmetic outcomes are of secondary concern, but where feasible, surgeries with better cosmetic outcomes can be considered in men as well.
Retrospective studies indicate that breast-conserving surgery can be performed in carefully selected patients. Male breast cancer patients who present with locally advanced tumors (ie, T3, T4) can be offered therapy similar to that for locally advanced breast cancer in women, with neoadjuvant chemotherapy followed by surgical resection.
Principles of radiation therapy are same as in breast cancer in women. No randomized controlled studies have evaluated radiation therapy in men with breast cancer; instead, the recommendations are based on evidence derived from data from clinical trials in women. One difference is that most expert opinion suggests a lower threshold for recommending radiation therapy in men than in women, due to the anatomy of the male breast. The typical indication for adjuvant radiation includes T3 or higher tumor stage, four or more positive lymph nodes, and positive surgical margins.
Recomendations for use of systemic therapy in male breast cancer are generally the same as in female breast cancer, because the rarity of male breast cancer has precluded the performance of clinical studies. Tamoxifen is the recommended adjuvant endocrine therapy. Duration is at least 5 years and in appropriate patients can be extended to 10 years, given the results of the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial.
No data support the use of aromastase inhibitors in men. In fact, a retrospective study indicates that aromatase inhibitors may be associated with poorer outcomes when compared with tamoxifen. Use of adjuvant chemotherapy mirrors the use in women with breast cancer.
Most cases of metastatic male breast cancer are estrogen receptor (ER)–positive, and guidelines from the European School of Oncology and the European Society of Medical Oncology recommend endocrine treatment with tamoxifen as the preferred option for these patients, unless they have suspected or proven endocrine resistance or rapidly progressive disease that requires a fast response. Second-line hormonal approaches include orchiectomy, aromatase inhibitors, and androgen ablation. However, chemotherapy can also provide palliation.
Long term monitoring
Men who have had breast cancer are at increased risk for a second ipsilateral or contralateral breast cancer. The risk of subsequent contralateral breast cancer is highest in men who were younger than 50 years when their initial cancer was diagnosed. Thus, periodic screening is probably advisable.
Source: Medscape Online