BACKGROUND Most patients with hormone receptor (HR)-positive, human epidermal growth factor receptor type 2 (HER2)-negative breast cancer can be cured by surgery and endocrine therapy, but a significant proportion suffer recurrences. Actinin-4 is associated with cancer invasion and metastasis, and its genetic alteration may be used for breast cancer prognostication. METHODS The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridisation (FISH) in two independent cohorts totalling 597 patients (336 from Japan and 261 from the USA) with HR-positive, HER2-negative, node-negative breast cancer. RESULTS In the Japanese cohort, multivariate analysis revealed that a copy number increase (CNI) of ACTN4 was an independent factor associated with high risks of recurrence (P = 0.01; hazard ratio (HR), 2.95) and breast cancer death (P = 0.014; HR, 4.27). The prognostic significance of ACTN4 CNI was validated in the US cohort, where it was the sole prognostic factor significantly associated with high risks of recurrence (P = 0.04; HR, 2.73) and death (P = 0.016; HR, 4.01). CONCLUSIONS Copy number analysis of a single gene, ACTN4, can identify early-stage luminal breast cancer patients with a distinct outcome. Such high-risk patients may benefit from adjuvant chemotherapy.

中文翻译：

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ACTN4基因拷贝数改变对激素受体阳性，HER2阴性，淋巴结阴性的浸润性乳腺癌的预后影响。

背景技术大多数具有激素受体（HR）阳性，人类表皮生长因子受体2型（HER2）阴性的乳腺癌患者可以通过手术和内分泌疗法治愈，但是相当一部分患者会复发。肌动蛋白4与癌症的侵袭和转移有关，其遗传改变可用于乳腺癌的预后。方法通过荧光原位杂交（FISH）法测定两个独立的队列，共597例患者（日本为336例，美国为261例）HR阳性，HER2阴性的淋巴结，检测肌动蛋白4（ACTN4）基因的拷贝数。 -阴性乳腺癌。结果在日本队列中，多变量分析显示ACTN4的拷贝数增加（CNI）是与高复发风险相关的独立因素（P = 0.01；危险比（HR），2。95）和乳腺癌死亡（P = 0.014; HR，4.27）。ACTN4 CNI的预后意义在美国队列中得到验证，这是与高复发风险（P = 0.04； HR，2.73）和死亡（P = 0.016； HR，4.01）显着相关的唯一预后因素。结论对单个基因ACTN4的拷贝数分析可以鉴定出具有明显结果的早期腔内乳腺癌患者。这类高危患者可能会从辅助化疗中受益。可以识别出具有明显结果的早期腔内乳腺癌患者。这类高危患者可能会从辅助化疗中受益。可以识别出具有明显结果的早期腔内乳腺癌患者。这类高危患者可能会从辅助化疗中受益。