The majority of men with early stage disease underwent modified radical mastectomy (96%), but ~50% of patients with node positive disease (who could potentially benefit from postoperative radiation) did not receive it. One-third of men received adjuvant or neoadjuvant chemotherapy, with a trend toward more chemotherapy administration over time. Only 5% of tumors were positive for HER-2 and 1% were triple negative for the estrogen receptor, progesterone receptor, and HER-2. Interestingly, although >90% of men had hormone receptor positive disease, only 77% received any adjuvant endocrine therapy. Amongst those who did receive endocrine therapy, tamoxifen monotherapy was utilized in 88%, and aromatase inhibitor was administered alone or in sequence with tamoxifen in 9%.
Most men with estrogen receptor positive early stage breast cancer receive tamoxifen because it is unclear whether aromatase inhibitors adequately reduce their estrogen levels in the absence of concurrent gonadotropin-releasing hormone agonist (GnRH-a) administration. When there is a contraindication to tamoxifen use (eg, a history of pulmonary embolus, though the clot risk associated with tamoxifen is poorly studied in men), aromatase inhibitors are considered with or without GnRH-a.22
Because the age-standardized incidence of male breast cancer is only 1/100,000 person-years with a lifetime risk of 1/1,000,23–26 there is no role for screening breast tissue in the general male population. On the other hand, the risk of a new breast cancer (contralaterally in those who have had mastectomy) is significantly higher in a male breast cancer survivor than in the general population. A study from the Surveillance, Epidemiology, and End Results database that included 1,788 male breast cancers demonstrated a 30-fold increased risk of developing a contralateral breast cancer (SIR [standardized incidence ratio] =29.64, 95% CI [confidence interval] 15–52) compared to the general population of men, while female breast cancer survivors only had a two- to fourfold increased risk compared to the general population of women.27 This elevated risk was greatest in men who were younger than 50 years when first diagnosed with breast cancer (SIR 110.29, 95% CI 13.33–401.32). Risk of second breast cancers did not seem to be impacted by receipt of radiation in this study. In a Swedish cohort study that included 457 men with breast cancer, Dong and Hemminki reported a 93-fold (95% CI 39–84) increased risk of a second breast cancer in men and only a threefold increase in women. The risk was highest in the men in whom >10 years had passed since their initial breast cancer diagnosis, but the absolute risk was low (<2% over a 38-year follow-up period).28 Therefore, it is possible but not certain that routine mammographic imaging of residual breast tissue could be of value in male breast cancer survivors. Male survivors carrying BRCA mutations and those with other conditions known to predispose to new primary cancers (eg, Klinefelter’s syndrome) likely have higher rates of future new breast cancers, and therefore could benefit most from breast imaging.
Male breast cancer survivors are at risk of certain non-breast second malignancies. Cutuli et al reported that 17% of a cohort of 404 male breast cancer patients later developed at least one other primary malignancy (including prostate, lung, colorectal and esophageal cancers).29 A recent study by Masci et al revealed that 18% of male breast cancer survivors developed a second cancer over a median follow-up time of 51.5 months (range: 0.5–219 months), with prostate cancer (31%) and colon cancer (19%) being the most common. Other second neoplasms included gastric cancer, lung cancer, sarcoma, bilateral renal cancer, and leukemia. The median age at diagnosis of the second malignancy was 70 years (range: 54–82 years). Among the patients in this study who developed second neoplasms, approximately one-half had received anthracycline-based chemotherapy for their breast cancers, approximately three-quarters had received endocrine therapy, and 19% had undergone adjuvant radiation treatments. However, it is uncertain whether or not a common genetic cause or toxicities of breast cancer treatments contributed to the development of these second cancers. BRCA testing results were not available for the majority of the patients in this study, but it is possible that hereditary cancer syndromes contributed to these findings. The one patient who developed sarcoma after breast cancer was known to carry a BRCA1 mutation.30 Interestingly, Auvinen et al reported no increase in nonbreast cancer risk in their analysis of 1,788 male breast cancer patients from the Surveillance, Epidemiology, and End Results registry (SIR =0.99, 95% CI 0.86–1.1).27
The Swedish cancer database study published by Dong and Hemminki did show a higher risk for second cancers and highlighted that there may be a special link between breast cancer and prostate cancer.28 Prostate cancer is the most common malignancy in males, with an incidence that rises with age. Patients with family histories significant for prostate cancer carry an increased risk of breast cancer and vice versa.31,32 Also, Thellenberg et al found in another large Swedish cohort study that men previously diagnosed with prostate cancer had a higher risk of breast cancer.33 This breast–prostate cancer link may be related to BRCA2 mutations and/or to the hormonal milieu, both of which can predispose to both neoplasms.34,35
Cancer screening recommendations
Much remains to be learned about optimal surveillance strategies in men with breast cancer. At this point, we believe that male survivors of early stage breast cancer should be offered the same annual mammography of residual breast tissue for early detection of second breast cancers as female survivors (though the value of breast imaging remains uncertain in men) and the same screening programs for non-breast cancers as men in the general population, unless they are found to carry deleterious genetic mutations for which specific follow-up is recommended.
Extrapolating from National Comprehensive Cancer Network (NCCN) guidelines for female breast cancer survivors, it is likely appropriate to suggest that male breast cancer survivors undergo history and physical examination (including chest wall/breast examination) twice yearly for the first 5 years of surveillance and then annually thereafter. Laboratory testing and nonbreast imaging are recommended only in the setting of clinical suspicion of relapse or recurrence based on new or worsening symptoms.36