Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Mod Pathol. 2020 Dec;33(12):2473-2482. doi: 10.1038/s41379-020-0589-x. Epub 2020 Jun 5.
Pure invasive apocrine carcinoma is a rare type of primary breast cancer, constituting ~1% of all breast cancers. Since most pure invasive apocrine carcinomas are triple negative, the lack of targeted therapies for triple-negative breast cancer has fostered efforts to discover actionable molecular targets in these tumors. In this study, we analyzed the clinicopathologic characteristics and comprehensive genomic profiling of 18 patients with pure triple-negative apocrine carcinomas (TNACs) using a 324-gene panel assay (FoundationOne CDx). The median age of these patients was 55.5 years, and the postmenopausal status rate was 77.8%. In total, 83.3% of patients were diagnosed with histological grade II, and 16.7% were diagnosed with grade III. The majority of patients presented at an early tumor-node-metastasis (TNM) stage (I: 38.9%; II: 50.0%; and III: 11.1%). The mean Ki-67 index was 9.7%, and the percent of PD-L1 positivity was 11.7%. With a median follow-up period of 76.5 months, one patient died, and two experienced distant metastases. There were 61 clinically relevant genomic alterations among all 18 pure TNACs, and the mean tumor mutation burden (TMB) was 3 Mut/Mb. The top ranked altered genes were PIK3CA (72.2%), PTEN (33.3%) and TP53 (27.8%). There were four novel mutations found in PTEN and an actionable rearrangement involving FGFR2-TACC2 that has not been reported in breast cancer before. In total, 88.9%, 50%, 44.4%, and 16.7% of TNACs had at least one clinically relevant genomic alteration in genes involved in the PI3K/mTOR, cell cycle, RAS/RAF/MEK and growth factor receptor-related pathways, respectively. All patients had at least one clinically relevant genomic alteration, and 94.4% had at least one actionable alteration. To the best of our knowledge, this study is the largest genomic sequencing cohort of pure TNACs. Incorporation of comprehensive genomic profiling into TNACs might shed light on potential therapeutic opportunities for both targeted drugs and immune checkpoint inhibitors.
纯浸润性大汗腺癌是一种罕见的原发性乳腺癌，约占所有乳腺癌的 1%。由于大多数纯浸润性大汗腺癌均为三阴性乳腺癌，缺乏针对三阴性乳腺癌的靶向治疗方法，促使人们努力在这些肿瘤中发现可操作的分子靶点。在这项研究中，我们使用 324 基因panel 检测（FoundationOne CDx）分析了 18 例纯三阴性大汗腺癌（TNAC）患者的临床病理特征和综合基因组谱。这些患者的中位年龄为 55.5 岁，绝经后状态率为 77.8%。总共，83.3%的患者诊断为组织学 II 级，16.7%诊断为 III 级。大多数患者处于早期肿瘤-淋巴结-转移（TNM）分期（I 期：38.9%；II 期：50.0%；III 期：11.1%）。平均 Ki-67 指数为 9.7%，PD-L1 阳性率为 11.7%。中位随访时间为 76.5 个月，1 例患者死亡，2 例发生远处转移。在所有 18 例纯 TNAC 中，共发现 61 个临床相关的基因组改变，平均肿瘤突变负荷（TMB）为 3 Mut/Mb。排名最高的改变基因是 PIK3CA（72.2%）、PTEN（33.3%）和 TP53（27.8%）。在 PTEN 中发现了 4 个新突变，以及一个之前在乳腺癌中未报道过的 FGFR2-TACC2 可操作重排。总共，88.9%、50%、44.4%和 16.7%的 TNAC 分别在参与 PI3K/mTOR、细胞周期、RAS/RAF/MEK 和生长因子受体相关途径的基因中至少存在一个临床相关的基因组改变。所有患者均存在至少一种临床相关的基因组改变，94.4%的患者存在至少一种可操作的改变。据我们所知，这项研究是最大的纯 TNAC 基因组测序队列。将综合基因组谱纳入 TNAC 可能为靶向药物和免疫检查点抑制剂提供潜在的治疗机会。
