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Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.

乳腺浸润性大汗腺癌: 18 例纯三阴性大汗腺癌的临床病理特征和综合基因组谱。

  • 影响因子:6.13
  • DOI:10.1038/s41379-020-0589-x
  • 作者列表:"Sun X","Zuo K","Yao Q","Zhou S","Shui R","Xu X","Bi R","Yu B","Cheng Y","Tu X","Lu H","Yang W
  • 发表时间:2020-06-05
Abstract

: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.

摘要

: 单纯浸润性大汗腺癌是原发性乳腺癌的一种罕见类型,约占所有乳腺癌的 1%。由于大多数纯侵袭性大汗腺癌是三阴性的,三阴性乳腺癌靶向治疗的缺乏促进了在这些肿瘤中发现可操作的分子靶点的努力。在本研究中,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 (TNACs) 患者的临床病理特征和全面的基因组谱。这些患者的中位年龄为 55.5 岁,绝经后状态率为 77.8%。总的来说,83.3% 的患者被诊断为组织学 ⅱ 级,16.7% 的患者被诊断为 ⅲ 级。大多数患者表现为早期肿瘤-淋巴结-转移 (TNM) 分期 (I: 38.9%; II: 50.0%; 和 III: 11.1%)。平均 Ki-67 指数为 9.7%,PD-L1 阳性率为 11.7%。中位随访期为 76.5 个月,1 例患者死亡,2 例发生远处转移。在所有 18 个纯 TNACs 中有 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。排名靠前的改变基因为 PIK3CA (72.2%) 、 PTEN (33.3%) 和 TP53 (27.8%)。在 PTEN 中发现了四个新的突变和一个涉及 FGFR2-TACC2 的可操作的重排,这在乳腺癌中以前没有报道过。总共有 88.9% 、 50% 、 44.4% 和 16.7% 的 TNACs 在参与 PI3K/mTOR 、细胞周期的基因中至少有一个临床相关的基因组改变,分别为 RAS/RAF/MEK 和生长因子受体相关通路。所有患者至少有一个临床相关的基因组改变,94.4% 至少有一个可操作的改变。据我们所知,这项研究是纯 TNACs 最大的基因组测序队列。将全面的基因组谱纳入 TNACs 可能揭示靶向药物和免疫检查点抑制剂的潜在治疗机会。

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影响因子:2.87
发表时间:2020-01-31
来源期刊:Bioscience reports
DOI:10.1042/BSR20192546
作者列表:["Chen X","Theobard R","Zhang J","Dai X"]

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发表时间:2020-01-31
来源期刊:BMC cancer
DOI:10.1186/s12885-020-6534-z
作者列表:["Soliman H","Shah V","Srkalovic G","Mahtani R","Levine E","Mavromatis B","Srinivasiah J","Kassar M","Gabordi R","Qamar R","Untch S","Kling HM","Treece T","Audeh W"]

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