基于 PAM50 的化疗内分泌评分（CES）在接受抗 HER2 新辅助治疗的激素受体阳性 HER2 阳性乳腺癌中的独立验证。
Independent Validation of the PAM50-Based Chemo-Endocrine Score (CES) in Hormone Receptor-Positive HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2-Based Therapy.
机构信息
Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Department of Medical Oncology, Hospital Clínic de Barcelona, Spain.
出版信息
Clin Cancer Res. 2021 Jun 1;27(11):3116-3125. doi: 10.1158/1078-0432.CCR-20-4102. Epub 2021 Feb 25.
PURPOSE
We do not yet have validated biomarkers to predict response and outcome within hormone receptor-positive/HER2-positive (HR+/HER2+) breast cancer. The PAM50-based chemo-endocrine score (CES) predicts chemo-endocrine sensitivity in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer. Here, we evaluate the relationship of CES with response and survival in HR+/HER2+ breast cancer.
EXPERIMENTAL DESIGN
Intrinsic subtype and clinicopathologic data were obtained from seven studies in which patients were treated with HER2-targeted therapy either with endocrine therapy (ET) or with chemotherapy (CTX). CES was evaluated as a continuous variable and categorically from low to high scores [CES-C (chemo-sensitive), CES-U (uncertain), and CES-E (endocrine-sensitive)]. We first analyzed each dataset individually, and then all combined. Multivariable analyses were used to test CES association with pathologic complete response (pCR) and disease-free survival (DFS).
RESULTS
A total of 457 patients were included (112 with ET and 345 with CTX). In the combined cohort, CES-C, CES-U, and CES-E were identified in 60%, 23%, and 17% of the patients, respectively. High CES (i.e., CES-E) was associated with a lower probability of achieving pCR independently of clinical characteristics, therapy, intrinsic subtype, and study (adjusted OR = 0.42; = 0.016). A total of 295 patients were analyzed for DFS with a median follow-up of 66 months. High CES was also associated with better DFS (adjusted HR, 0.174; = 0.003) independently of pCR, clinical characteristics and intrinsic subtype. In patients with residual disease, the adjusted DFS HR of CES was 0.160 ( = 0.012).
CONCLUSIONS
In HER2+/HR+ breast cancer, CES is useful for predicting chemo-endocrine sensitivity and provides additional prognostication beyond intrinsic subtype and clinicopathologic characteristics.
目的
我们目前还没有经过验证的生物标志物来预测激素受体阳性/HER2 阳性（HR+/HER2+）乳腺癌的反应和预后。基于 PAM50 的化疗-内分泌评分（CES）可预测激素受体阳性/HER2 阴性（HR+/HER2-）乳腺癌的化疗-内分泌敏感性。在这里，我们评估了 CES 与 HR+/HER2+乳腺癌的反应和生存之间的关系。
实验设计
从接受 HER2 靶向治疗的 7 项研究中获得了内在亚型和临床病理数据，这些研究中患者接受了内分泌治疗（ET）或化疗（CTX）。CES 被评估为连续变量和分类变量（CES-C[化疗敏感]、CES-U[不确定]和 CES-E[内分泌敏感]）。我们首先分别分析每个数据集，然后将所有数据集合并。多变量分析用于测试 CES 与病理完全缓解（pCR）和无病生存（DFS）的相关性。
结果
共纳入 457 例患者（112 例接受 ET，345 例接受 CTX）。在合并队列中，分别有 60%、23%和 17%的患者被诊断为 CES-C、CES-U 和 CES-E。高 CES（即 CES-E）与独立于临床特征、治疗、内在亚型和研究的 pCR 概率较低相关（调整后的 OR=0.42；P=0.016）。共对 295 例患者进行了 DFS 分析，中位随访时间为 66 个月。高 CES 也与更好的 DFS 相关（调整后的 HR，0.174；P=0.003），独立于 pCR、临床特征和内在亚型。在有残留疾病的患者中，CES 的调整后 DFS HR 为 0.160（P=0.012）。
结论
在 HER2+/HR+乳腺癌中，CES 可用于预测化疗-内分泌敏感性，并提供比内在亚型和临床病理特征更有价值的预后信息。
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