Table_1_Adjuvant chemotherapy is associated with an overall survival benefit regardless of age in ER+/HER2- breast cancer pts with 1-3 positive nodes and oncotype DX recurrence score 20 to 25: an NCDB analysis.docx

BackgroundThe RxPONDER trial found that among breast cancer patients with estrogen receptor positive (ER+) breast cancer, 1-3 positive axillary nodes, and a recurrence score of ≤25, only pre-menopausal women benefitted from adjuvant chemoendocrine therapy; postmenopausal women with similar characteristic did not benefit from adjuvant chemotherapy. We aimed to replicate the RxPonder trial using a larger patient cohort with real world data to determine whether a RS threshold existed where adjuvant chemotherapy was beneficial regardless of age.
MethodsThe National Cancer Database (NCDB) was queried for women with ER+, human epidermal growth factor receptor 2 (HER2) negative breast cancer, 1-3 positive axillary nodes, and RS ≤25 who received endocrine (ET) only or chemo-endocrine therapy (CET). Cox regression interaction was explored between CET and age as a surrogate for menopausal status.
ResultsThe final analytic cohort included 28,427 eligible women: 7,487 (26.3%) received adjuvant CET and 20,940 (73.7%) ET. In the entire cohort, RS had a normal distribution, with a median score of 14. After correcting for demographic and clinical variables, a threshold effect was observed with RS >20 being associated with a significantly inferior overall survival (OS) (P value range: < 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age <=50: HR = 0.334, P=0.002; age>50: HR=0.521, P=0.019).
ConclusionAmong women with ER+/HER2- breast cancer with 1–3 positive nodes, and a RS of 20-25—in contrast to the RxPONDER trial—we observed that CET was associated with an OS benefit in women regardless of age.

背景：RxPONDER试验发现，在雌激素受体阳性（ER+）、1~3枚腋窝淋巴结阳性且复发评分（RS）≤25的乳腺癌患者中，仅绝经前女性可从辅助化疗内分泌治疗中获益；具有上述相似特征的绝经后女性则未从辅助化疗中获益。本研究旨在利用更大样本量的真实世界数据队列复刻RxPONDER试验，以明确是否存在无论年龄如何均能从辅助化疗中获益的RS阈值。方法：本研究检索美国国家癌症数据库（NCDB）中符合以下条件的女性患者：ER+、人类表皮生长因子受体2（HER2）阴性、1~3枚腋窝淋巴结阳性、RS≤25，且仅接受内分泌治疗（ET）或化疗内分泌联合治疗（CET）。以年龄作为绝经状态的替代指标，探究CET与年龄之间的Cox回归交互作用。结果：最终分析队列共纳入28427例符合入组标准的女性患者，其中7487例（26.3%）接受辅助化疗内分泌联合治疗（CET），20940例（73.7%）仅接受内分泌治疗（ET）。全队列中复发评分（RS）呈正态分布，中位评分为14。校正人口统计学特征与临床变量后，观察到阈值效应：RS>20与总生存期（OS）显著更差相关（P值范围：<0.001~0.019）。在RS为20~25的女性中，无论年龄如何，CET均与总生存期（OS）的显著改善相关（年龄≤50岁：风险比HR=0.334，P=0.002；年龄>50岁：风险比HR=0.521，P=0.019）。结论：与RxPONDER试验结果不同，在1~3枚腋窝淋巴结阳性、RS为20~25的ER+/HER2-乳腺癌女性患者中，我们观察到无论年龄如何，化疗内分泌联合治疗（CET）均与总生存期（OS）获益相关。