André Saudade, Pereira Teresa, Silva Fernanda, Machado Patrícia, Vaz Fátima, Aparício Mariana, Silva Giovani L, Pinto António E
Department of Pathology, Portuguese Institute of Oncology of Lisbon, 1099-023 Lisbon, Portugal.
NOVA Medical School, NOVA University, 1169-056 Lisbon, Portugal.
Mol Clin Oncol. 2019 Jun;10(6):644-654. doi: 10.3892/mco.2019.1841. Epub 2019 Apr 8.
Male breast cancer (BC) represents an individual subtype of BC, with therapeutic procedures based on female BC therapy results. The present study evaluated the parameters currently used for the characterization and therapy of male BC, and their association with disease-free (DFS) and overall survival (OS), aiming to obtain a comprehensive basis to improve the personalized care of male BC. A total of 196 patients from March 1970 to March 2018 (mean follow-up, 84.9 months) were profiled, using clinicopathological review, molecular assessment [BRCA1/2, DNA repair associated (BRCA1/2) status, immunohistochemistry, fluorescence hybridization and DNA flow cytometry] and Cox regression statistical analysis. The median age of patients was 66.5 years. At presentation, 39.2% of patients with invasive carcinomas were in anatomic stage (AS) I. Patients exhibited primarily invasive carcinomas of no special type, histological grade 2, estrogen receptor α-(ERα) and progesterone receptor (PR)-positive, receptor tyrosine kinase erbB-2-negative, high Ki-67, Luminal B-like and aneuploid tumors. A total of 13 of the 44 (29.5%) BRCA-evaluated patients exhibited BRCA2 mutations, significantly associated with family history (FH), bilaterality, high Ki-67 expression, absence of PR and Luminal B-like tumors. Bilaterality was associated with the occurrence of non-breast primary neoplasms (NBPN). The 5 and 10-year DFS rates, excluding patients with distant metastasis, NBPN and carcinomas (n=145) were 65.9 and 58.2%, respectively, and the 5 and 10-year OS rates were 77.5 and 59.2%, respectively. In the univariate analysis, Luminal B-like subtype, BRCA2 mutations, high Ki-67 expression, and AS II and III were significantly associated with shorter DFS and OS. In addition, age >70 years was associated with low OS. In the multivariate analysis, FH, AS II and III, and Luminal B-like subtypes were associated with poorer OS. In conclusion, the data from the present study emphasize the high incidence of BRCA2 mutation in male BC, and its association with FH, bilaterality, high Ki-67 expression, negative PR expression and Luminal B-like subtypes, and with shorter DFS and OS in univariate analysis.
男性乳腺癌(BC)是乳腺癌的一种独特亚型,其治疗方法基于女性乳腺癌的治疗结果。本研究评估了目前用于男性乳腺癌特征描述和治疗的参数,以及它们与无病生存期(DFS)和总生存期(OS)的关联,旨在为改善男性乳腺癌的个性化护理获得全面依据。对1970年3月至2018年3月期间的196例患者(平均随访84.9个月)进行了分析,采用临床病理检查、分子评估[BRCA1/2、DNA修复相关(BRCA1/2)状态、免疫组织化学、荧光杂交和DNA流式细胞术]以及Cox回归统计分析。患者的中位年龄为66.5岁。就诊时,39.2%的浸润性癌患者处于解剖学分期(AS)I期。患者主要表现为非特殊类型的浸润性癌,组织学分级为2级,雌激素受体α(ERα)和孕激素受体(PR)阳性,受体酪氨酸激酶erbB-2阴性,Ki-67高表达,Luminal B样和非整倍体肿瘤。在44例接受BRCA评估的患者中,共有13例(29.5%)出现BRCA2突变,这与家族史(FH)、双侧性、高Ki-67表达、PR缺失和Luminal B样肿瘤显著相关。双侧性与非乳腺原发性肿瘤(NBPN)的发生有关。排除远处转移、NBPN和原位癌患者(n = 145)后,5年和10年DFS率分别为65.9%和58.2%,5年和10年OS率分别为77.5%和59.2%。在单因素分析中,Luminal B样亚型、BRCA2突变、高Ki-67表达以及AS II和III期与较短的DFS和OS显著相关。此外,年龄>70岁与低OS相关。在多因素分析中,FH、AS II和III期以及Luminal B样亚型与较差的OS相关。总之,本研究数据强调了男性乳腺癌中BRCA2突变的高发生率,及其与FH、双侧性、高Ki-67表达、PR阴性表达和Luminal B样亚型的关联,以及在单因素分析中与较短的DFS和OS的关联。