背景:男性乳腺癌(MaBC)关于基因组改变的数据有限。我们旨在全面描述和比较MaBC的基因组学与女性乳腺癌(FBC)的亚型。
方法:使用基础医学的基因组数据,我们将253MaBC分为雌激素受体(ER)阳性/人表皮生长因子受体2(HER2)阴性(n=210),ER阳性/HER2阳性(n=22)和三阴性(n=20)。1例ER阴性/HER2阳性病例因n-of-1而被排除。将最终MaBC队列(n=252)的基因组学与按分子亚型分层的FBC队列(n=2708)进行比较,调整后的p值。在整个MaBC和FBC队列中,我们比较了癌症易感基因(CSG)(ATM/BRCA1/BRCA2/CHEK2/PALB2)的突变患病率.
结果:比较ER阳性/HER2阴性病例,MaBc在GATA3中的改变增加(26.2%与15.9%,p=0.005),BRCA2(13.8%vs.5.3%,p<0.001),MDM2(13.3%与6.14%,p=0.004)和CDK4(7.1%与1.8%,p<0.001);TP53的频率降低(11.0%vs.42.6%,p<0.001)和ESR1突变(5.7%vs.14.6%,p<0.001)。比较ER阳性/HER2阳性病例,MaBC在ERBB2中的短变体增加(22.7%vs.0.6%,p=0.002),GATA3(36.3%vs.6.2%,p=0.004),和MDM2(36.3%与4.9%,p=0.002);在MaBC与FBC中观察到TP53改变的频率降低(9.1%与61.7%,p<0.001)。在三阴性病例中,与FBC相比,MaBC的TP53改变减少(25.0%vs.84.4%,p<0.001)。MaBC的CSG变异频率高于FBC(22.6%vs.14.6%,p<0.05),MaBC中BRCA突变增加(14.6%vs.9.1%,p<0.05)。
结论:尽管MaBC和FBC有一些共同的改变,我们的研究揭示了与肿瘤生物学相关的几个重要差异以及靶向治疗的意义.
BACKGROUND: Male breast cancer (MaBC) has limited data on genomic alterations. We aimed to comprehensively describe and compare MaBC\'s genomics with female breast cancer\'s (FBC) across subtypes.
METHODS: Using genomic data from Foundation Medicine, we categorized 253 MaBC into estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 210), ER-positive/HER2-positive (n = 22) and triple-negative (n = 20). One ER-negative/HER2-positive case was excluded due to n-of-1. The genomics of the final MaBC cohort (n = 252) were compared to a FBC cohort (n = 2708) stratified by molecular subtype, with adjusted p-values. In the overall MaBC and FBC cohorts, we compared mutational prevalence in cancer susceptibility genes (CSG) (ATM/BRCA1/BRCA2/CHEK2/PALB2).
RESULTS: Comparing ER-positive/HER2-negative cases, MaBc had increased alterations in GATA3 (26.2% vs. 15.9%, p = 0.005), BRCA2 (13.8% vs. 5.3%, p < 0.001), MDM2 (13.3% vs. 6.14%, p = 0.004) and CDK4 (7.1% vs. 1.8%, p < 0.001); and decreased frequency of TP53 (11.0% vs. 42.6%, p < 0.001) and ESR1 mutations (5.7% vs. 14.6%, p < 0.001). Comparing ER-positive/HER2-positive cases, MaBC had increased short variants in ERBB2 (22.7% vs. 0.6%, p = 0.002), GATA3 (36.3% vs. 6.2%, p = 0.004), and MDM2 (36.3% vs. 4.9%, p = 0.002); decreased frequency of TP53 alterations was seen in MaBC versus FBC (9.1% vs. 61.7%, p < 0.001). Within triple-negative cases, MaBC had decreased alterations in TP53 compared to FBC (25.0% vs. 84.4%, p < 0.001). MaBC had higher frequency of CSG variants than FBC (22.6% vs. 14.6%, p < 0.05), with increased BRCA mutations in MaBC (14.6% vs. 9.1%, p < 0.05).
CONCLUSIONS: Although MaBC and FBC share some common alterations, our study revealed several important differences relevant to tumor biology and implications for targeted therapies.