BACKGROUND:Male breast cancer (MBC) is a rare and scarcely investigated disease. The strongest genetic risk factor for MBC is represented by inherited BRCA2 mutations, whereas the association between MBC and BRCA1 mutations is less clear. MBC appears to be biologically similar to breast cancer in females, however the phenotypic characteristics of BRCA1/2-related MBCs are not yet well elucidated. OBJECTIVE:To investigate the genetic and phenotypic characteristics of MBC in a large and well-characterized population-based series of 108 MBCs from Tuscany (Central Italy) and to evaluate associations between BRCA1/BRCA2 mutation status and clinical-pathological features including breast/ovarian cancer first-degree family history, tumor histology and grade, proliferative activity, estrogen/progesterone receptors (ER/PR) and epidermal growth factor receptor 2 (HER2) expression. Results BRCA1/BRCA2 mutations were identified in ten MBCs, in particular, two cases (1.9%) carried BRCA1 and eight cases (7.4%) carried BRCA2 mutations. The same BRCA1 mutation (3347delAG) was detected in two unrelated MBC cases. Three novel BRCA2 pathogenic mutations were found. Statistically significant associations emerged between BRCA2-related tumors and absence of PR expression (P = 0.008), HER2 over-expression (P = 0.002) and high tumor grade (P = 0.005). Conclusions Here, we (i) reported that in our population about 9% of MBC cases are accounted for by BRCA1/BRCA2 mutations; (ii) enlarged the BRCA2 mutational spectrum and (iii) characterized a specific phenotype associated with BRCA2-related MBCs suggestive of aggressive behavior. Overall, our results may have important implications on clinical management for this rare disease.

译文

背景:男性乳腺癌(MBC)是一种罕见且鲜有研究的疾病。 MBC的最强遗传风险因子由遗传的BRCA2突变代表,而MBC和BRCA1突变之间的关联尚不清楚。在女性中,MBC在生物学上似乎与乳腺癌相似,但是与BRCA1 / 2相关的MBC的表型特征尚未得到很好的阐明。
目的:研究来自托斯卡纳(意大利中部)的一个大型且特征明确的基于人群的108 MBCs系列中MBC的遗传和表型特征,并评估BRCA1 / BRCA2突变状态与临床病理特征(包括乳腺癌/卵巢癌)之间的关联癌症一级家族史,肿瘤组织学和等级,增殖活性,雌激素/孕激素受体(ER / PR)和表皮生长因子受体2(HER2)的表达。结果在10个MBCs中鉴定出BRCA1 / BRCA2突变,特别是2例(1.9%)携带BRCA1,8例(7.4%)携带BRCA2突变。在两个无关MBC病例中检测到相同的BRCA1突变(3347delAG)。发现了三个新的BRCA2致病突变。在与BRCA2相关的肿瘤与PR表达缺失(P = 0.008),HER2过表达(P = 0.002)和高肿瘤分级(P = 0.005)之间,出现了统计学上显着的关联。结论在这里,我们(i)报告说,在我们的人群中,约9%的MBC病例是由BRCA1 / BRCA2突变引起的; (ii)扩大了BRCA2突变谱,并且(iii)表征了与BRCA2相关的MBC相关的特定表型,暗示了攻击行为。总体而言,我们的结果可能会对这种罕见疾病的临床治疗产生重要影响。

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