Background: The present study was performed to determine whether the human epidermal growth factor receptor-related 2 (HER2)/centromeric probe for chromosome 17 fluorescence in situ hybridization (FISH) ratio is a predictor of a pathologic complete response (pCR), recurrence-free survival (RFS), and/or overall survival (OS) in patients receiving neoadjuvant systemic treatment (NST) with trastuzumab (NST-T) for HER2+ locally advanced breast cancer (LABC).
Patients and methods: The present retrospective study included 555 patients with HER2+ LABC who had undergone NST and definitive surgery (1999-2012); 373 had concurrently received trastuzumab. HER2-positivity was considered present with an immunohistochemical score of 3+ and/or HER2 FISH ratio of ≥2.0. We used logistic regression analysis and Cox proportional hazard modeling to determine whether a high HER2 FISH ratio, either as a continuous variable or with a cutoff of ≥7.0, would predict for pCR (no invasive disease in the breast and no tumor in the ipsilateral axillary lymph nodes), RFS, and/or OS.
Results: The pCR group's median HER2 FISH ratio was significantly higher than that of the non-pCR group (6.4 vs. 5.2; p = .003). The logistic regression model demonstrated that the independent predictors of pCR included a high HER2 FISH ratio as a continuous variable (p = .04). The multicovariate Cox proportional hazard model showed that a high HER2 FISH ratio (with a cutoff of ≥7.0 or as a continuous variable) was a significant prognostic indicator of longer RFS time (p = .047 and p = .04, respectively). Similarly, a high HER2 FISH ratio of ≥7.0 was associated with longer OS (p = .06).
Conclusion: A high HER2 FISH ratio is a predictor of pCR in patients with HER2+ LABC who receive NST-T.
Implications for practice: This study demonstrated the optimal predictive and prognostic value of a HER2/centromeric probe for chromosome 17 FISH ratio for primary HER2+ breast cancer treated with trastuzumab combined with neoadjuvant systemic treatment (NST-T). This suggests that a high HER2 FISH ratio is a potential indicator for a high pathologic complete response rate and a better prognosis when patients are treated with NST-T.
摘要
背景. 本研究的目的是, 在接受新辅助系统治疗 (NST) 联合曲妥珠单抗 (NST-T) 治疗的人表皮生长因子受体 2 (HER2) 阳性的局部晚期乳腺癌 (LABC) 患者中, 确定 HER2/17 号染色体着丝粒探针荧光原位杂交(FISH) 比值是病理学完全缓解 (pCR)、无复发生存 (RFS) 和/或总生存 (OS) 的预测因素。
患者和方法. 本项回顾性研究在 1999 年∼2012 年间共纳入 555 例接受 NST 和根治术的 HER2+ LABC 患者, 373 例接受同期曲妥珠单抗治疗。免疫组化评分为 3+和/或 HER2 FISH 比值≥ 2.0 可判定为 HER2 阳性。我们使用 logistic 回归分析和 Cox 比例风险模型确定高 HER2 FISH 比值 (作为连续变量或者采用临界值≥7.0) 可预测 pCR (乳腺无浸润性疾病且同侧腋窝淋巴结无肿瘤)、RFS 和/或 OS。
结果. pCR组的中位HER2 FISH比值显著高于未达到pCR的患者 (6.4 vs 5.2, P = 0.003)。logistic 回归模型证实, 当高 HER2 FISH 比值作为连续变量时是 pCR 的独立预测因素 (P = 0.04)。多变量 Cox 比例风险模型显示, 高 HER2 FISH 比值 (采用临界值≥7.0 或作为连续变量) 是 RFS 持续时间较长的显著预后因素 (P值分别为 0.047 和 0.04)。与此相似, 当采用临界值≥7.0 时, 高 HER2 FISH 比值也与 OS 时间较长相关 (P = 0.06)。
结论. 高HER2 FISH 比值是接受NST-T治疗的HER2+ LABC患者pCR的预测因素。The Oncologist 2016;21:21–27
对临床实践的提示: 本研究证实, 对于接受曲妥珠单抗联合新辅助系统治疗 (NST-T) 的原发性 HER2+乳腺癌患者, HER2/17 号染色体着丝粒探针 FISH 比值具有理想的预测和预后价值。这提示对于接受 NST-T 治疗的患者, 高 HER2 FISH 比值是高病理学完全缓解率的潜在指标, 这类患者具有更好的预后。
Keywords: HER2+ breast cancer; HER2/centromeric probe for chromosome 17 fluorescence in situ hybridization ratio; Pathologic complete response; Predictive factor; Trastuzumab.
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