Male Breast Cancer: 37-Year Data Study at a Single Experience Center in Turkey

Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancer and less than 1% of all cancer cases, with less than 0.5% of all cancer deaths in men, annually [1].

MBC usually presents as a firm, painless mass along with palpable axillary nodes, nipple retraction, and ulceration of the skin at presentation. MBC is usually located in the subareolar region, but can also be seen in the upper outer quadrant [2]. As is the case with women, the left breast is involved more predominantly than the right breast, and approximately 1% all of cases are bilateral [2]. Approximately 90% of MBC are invasive ductal carcinomas. Lobular histology is rare, accounting for only 1.5% of MBC [2]. MBC has high rates of hormone-receptor expression; approximately 90% express oestrogen receptor (ER), and 81% express progesterone receptor (PR) [2]. Tumor size and lymph node involvement are important prognostic factors in MBC, as is for female breast cancer [2]. There are no prospective randomized trials comparing the efficacy of different treatment options for MBC. The standard surgical approach for localized MBC is a modified radical mastectomy (MRM), but as with women, retrospective studies suggest that equal effectiveness can be achieved with a radical mastectomy, MRM, or simple mastectomy in terms of local recurrence and survival [3, 4]. There is limited data regarding the indications for postmastectomy radiation therapy (RT) in men treated for breast cancer; the recommendation is to follow the same guidelines as for women. Postmastectomy RT appears to reduce locoregional recurrence in MBC; however, the influence on survival is unknown [5, 6]. Many retrospective studies have evaluated the role of adjuvant hormonal therapy, and these studies have revealed that most male patients can benefit from adjuvant tamoxifen in terms of recurrence and death [7, 8].

Adjuvant chemotherapy has been used to treat male and female patients with substantial risks of recurrence and death from breast cancer. Whereas the data supporting adjuvant chemotherapy in women is strong, there is little information on the effectiveness of adjuvant chemotherapy for MBC [7].

The aim of this study is to evaluate the effects of prognostic factors on overall survival (OS) and locoregional control (LC) among MBC patients treated at our institution over a 37-year period as weel as to review the related literature.

In our cohort, the median age for males with MBC was younger than those in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute [2]. Previously, some studies had shown an older median age for MBC compared to female breast cancer [1]. The median age in the current study was 62, whereas it was 67 years in a prior study [1]. Several studies from Sweden and Denmark suggested that men tended to be older than women at the time of diagnosis [10, 11]. In the current study, a hard, nontender mass was the main symptom of presentation. An earlier study revealed that the clinical presentation rate for the same type of mass for MBC was 75% to 95%. MBC has different biological features than female breast cancer. Previous studies have reported that 64.0% to 93.4% of men with breast carcinoma had an invasive ductal histology [2, 12], and only 1.5% were histologically lobular in nature [2]. However, in female breast cancer, 12% are lobular [2]. Most cases of MBC (86.8%) are invasive ductal carcinomas, with only 2.4% being lobular in our series. In some studies, most of the MBC tumors were of high grade [13], whereas other series have predominantly demonstrated grade 1 and grade 2 [14, 15]. In the present series, the majority of tumors in MBC had low and intermediate grades. In the previously reported series, the ER positivity rate was approximately 64% to 90% and PR positivity rate was between 70% and 81% in MBC [2, 16, 17]. In the present study, 70% of all patients had ER-positive and 65% had PR-positive disease. The c-erbB-2 status with immunochemistry has been determined in only 24 patients. Among these patients, two (8%) had the c-erbB-2 positive disease. A prior study of 75 patients found that only 5.3% of MBC patients overexpressed c-erbB-2. Similarly, Muir et al. [18] and Bloom et al. [19] discovered that only 1.7% overexpressed c-erbB-2, whereas 15% of MBC were c-erbB-2-positive in the European Institute of Oncology series [20].

Most predictors have been reported to affect the prognosis in MBC patients, with the tumor stage and axillary nodal status shown to be the most important independent predictors of OS [21]. Giordano et al. [2] found the 5-year OS rates of 78% for MBC patients with stage 1, 67% with stage II, 40% with stage III, and 19% with stage IV.

The 5-year OS rate was 76% for patients with a node negative disease and 54% for those with a node positive disease [2]. The tumor grade has been shown to affect the prognosis significantly in the univariate analysis; however, the significance of this association is not noted in the multivariate analysis [2, 22]. In the current study, the 5-year OS for patients with a node negative disease was 87.5% and 43.8% for those with a node positive disease; however, the tumor grade was not shown to affect the prognosis in the univariate analysis. Several studies have noted that ER and PR positivity predicted better OS in the univariate analysis; yet, this difference was not significant after the adjustments for the tumour stage and axillary lymph node status, in the multivariate analysis [2, 23]. The overexpression of c-erbB-2 has been associated with shortened survival in some studies [24]; however, others have failed to demonstrate a similar correlation [25, 26]. In our study, neither ER nor PR was shown to affect the prognosis in the univariate analysis. The principles of management for MBC have been extrapolated from the treatment of female breast cancer. Surgery is the basis of disease control. In our study, most of the patients were applied MRM (76%) and only 11% of the remaining underwent breast conservative surgery (lumpectomy axillary dissection). In the current study, as has been reported in previous studies, there was no significant difference in patients who underwent MRM compared with a conservative surgical procedure [3, 4]. In this study, 64 (74.4%) patients received adjuvant radiotherapy. The 5-year local relapse rate was 11.3%, and the most common local relapse sites were the chest wall and supraclavicular areas. Only the T stage was an independent prognostic factor for locoregional relapse. Perkins et al. [27] determined that for 142 patients who received RT, 18% had a locoregional relapse, with the most common site also being the chest wall and supraclavicular areas. They revealed that the margin status, the tumor size, and number of involved axillary lymph nodes were the predictors for locoregional relapse. There are a few small, retrospective studies which describe the use of postmastectomy radiation in MBC. In these studies, between 3% and 100% of the patients received RT, and the local recurrence rates ranged from 3% to 29% [28, 29]. Adjuvant chemotherapy and hormonal therapy were used in 45 (51%) and 28 (3%) patients, respectively. We did not evaluate the effects of hormonal treatment and chemotherapy for survival, because for the patients who received these adjuvant treatments, there was no homogeneity between the different stages, and there further, were not enough patients who received these treatments. In a SEER database review, which included 4,873 MBC cases diagnosed between 1973 and 2003, there was a 1.9% incidence of the second primary MBC [30]. We also determined a 2.3% risk for contralateral breast cancer in this 37-year follow-up study.

The main limitations of this study are its retrospective design and the limited number of cases. Also, there was no homogeneity based on adjuvant chemotherapy and hormonal therapy. Therefore, we did not evaluate their effects on survival.

In conclusion, we found that only tumor size and lymph node status were independent prognostic factors for survival. This agrees with the previous findings of the SEER database study [3]. However, ER and PR positivity along with the tumor grade had no effect on survival in the univariate analysis. Only the tumour size was an independent prognostic factor for locoregional relapse; MRM and conservative surgical procedures had similar outcomes for LC.