Piscuoglio Salvatore, Ng Charlotte K Y, Murray Melissa P, Guerini-Rocco Elena, Martelotto Luciano G, Geyer Felipe C, Bidard Francois-Clement, Berman Samuel, Fusco Nicola, Sakr Rita A, Eberle Carey A, De Mattos-Arruda Leticia, Macedo Gabriel S, Akram Muzaffar, Baslan Timour, Hicks James B, King Tari A, Brogi Edi, Norton Larry, Weigelt Britta, Hudis Clifford A, Reis-Filho Jorge S
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Pathology, European Institute of Oncology, Milan, Italy.
Clin Cancer Res. 2016 Aug 15;22(16):4045-56. doi: 10.1158/1078-0432.CCR-15-2840. Epub 2016 Mar 9.
Male breast cancer is rare, and its genomic landscape has yet to be fully characterized. Lacking studies in men, treatment of males with breast cancer is extrapolated from results in females with breast cancer. We sought to define whether male breast cancers harbor somatic genetic alterations in genes frequently altered in female breast cancers.
All male breast cancers were estrogen receptor-positive, and all but two were HER2-negative. Fifty-nine male breast cancers were subtyped by immunohistochemistry, and tumor-normal pairs were microdissected and subjected to massively parallel sequencing targeting all exons of 241 genes frequently mutated in female breast cancers or DNA-repair related. The repertoires of somatic mutations and copy number alterations of male breast cancers were compared with that of subtype-matched female breast cancers.
Twenty-nine percent and 71% of male breast cancers were immunohistochemically classified as luminal A-like or luminal B-like, respectively. Male breast cancers displayed a heterogeneous repertoire of somatic genetic alterations that to some extent recapitulated that of estrogen receptor (ER)-positive/HER2-negative female breast cancers, including recurrent mutations affecting PIK3CA (20%) and GATA3 (15%). ER-positive/HER2-negative male breast cancers, however, less frequently harbored 16q losses, and PIK3CA and TP53 mutations than ER-positive/HER2-negative female breast cancers. In addition, male breast cancers were found to be significantly enriched for mutations affecting DNA repair-related genes.
Male breast cancers less frequently harbor somatic genetic alterations typical of ER-positive/HER2-negative female breast cancers, such as PIK3CA and TP53 mutations and losses of 16q, suggesting that at least a subset of male breast cancers are driven by a distinct repertoire of somatic changes. Given the genomic differences, caution may be needed in the application of biologic and therapeutic findings from studies of female breast cancers to male breast cancers. Clin Cancer Res; 22(16); 4045-56. ©2016 AACR.
男性乳腺癌较为罕见，其基因组格局尚未得到充分表征。由于缺乏针对男性的研究，男性乳腺癌的治疗方案是根据女性乳腺癌的研究结果推断而来的。我们试图确定男性乳腺癌是否存在女性乳腺癌中常见的基因体细胞突变。
所有男性乳腺癌均为雌激素受体阳性，除两例外均为HER2阴性。通过免疫组织化学对59例男性乳腺癌进行亚型分类，对肿瘤-正常组织配对样本进行显微切割，并对女性乳腺癌中频繁突变或与DNA修复相关的241个基因的所有外显子进行大规模平行测序。将男性乳腺癌的体细胞突变和拷贝数改变情况与亚型匹配的女性乳腺癌进行比较。
分别有29%和71%的男性乳腺癌通过免疫组织化学分类为腔面A型或腔面B型。男性乳腺癌表现出体细胞基因改变的异质性，在一定程度上重现了雌激素受体（ER）阳性/HER2阴性女性乳腺癌的情况，包括影响PIK3CA（20%）和GATA3（15%）的复发性突变。然而，与ER阳性/HER2阴性女性乳腺癌相比，ER阳性/HER2阴性男性乳腺癌中16q缺失、PIK3CA和TP53突变的发生率较低。此外，发现男性乳腺癌中影响DNA修复相关基因的突变显著富集。
男性乳腺癌中ER阳性/HER2阴性女性乳腺癌典型的体细胞基因改变，如PIK3CA和TP53突变以及16q缺失，出现频率较低，这表明至少一部分男性乳腺癌是由不同的体细胞变化驱动的。鉴于基因组差异，将女性乳腺癌研究中的生物学和治疗学发现应用于男性乳腺癌时可能需要谨慎。临床癌症研究；22(16)；4045 - 56。©2016美国癌症研究协会。
