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TY - JOUR AU - Geyer, Charles E. AU - Tang, Gong AU - Mamounas, Eleftherios P. AU - Rastogi, Priya AU - Paik, Soonmyung AU - Shak, Steven AU - Baehner, Frederick L. AU - Crager, Michael AU - Wickerham, D. Lawrence AU - Costantino, Joseph P. AU - Wolmark, Norman PY - 2018 DA - 2018/11/14 TI - 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer JO - npj Breast Cancer SP - 37 VL - 4 IS - 1 AB - The NSABP B-20 prospective-retrospective study of the 21-gene Oncotype DX Breast Cancer Recurrence Score® test predicted benefit from addition of chemotherapy to tamoxifen in node-negative, estrogen-receptor positive breast cancer when recurrence score (RS) was ≥31. HER2 is a component of the RS algorithm with a positive coefficient and contributes to higher RS values. Accrual to B-20 occurred prior to routine testing for HER2, so questions have arisen regarding assay performance if HER2-positive patients were identified and excluded. We report an exploratory reanalysis of the B-20, 21-gene study following exclusion of such patients. Patients were considered HER2 positive if quantitative RT-PCR for HER2 was ≥11.5 units, and excluded from re-analyses performed using the original cutoffs: <18, 18–30, ≥31, and the TAILORx cutoffs: <11, 11–25, >25. The endpoint remained distant recurrence-free interval (DRFI) as in the original study. Distribution was estimated via the Kaplan–Meier method and compared via log-rank test. Multivariate Cox proportional hazards models estimated chemotherapy benefit in each group. In the RS < 18 and 18–30 groups, 1.7 and 6.7% were HER2 positive. In the RS ≥ 31 group, 41% were HER2 positive. Exclusion resulted in fewer events, with loss of significance for benefit from chemotherapy in the overall HER2-negative cohort (log-rank P = 0.06), but substantial benefit from chemotherapy remained in the RS ≥ 31 cohort (HR = 0.18; 95% CI: 0.07–0.47) and the RS > 25 cohort (HR = 0.28; 95% CI: 0.12–0.64). No benefit from chemotherapy was evident in the other RS groups. Following exclusion of HER2-positive patients based on RT-PCR expression, substantial benefit of chemotherapy remained for RS ≥ 31 as originally employed, and with RS > 25 employed in TAILORx. SN - 2374-4677 UR - https://doi.org/10.1038/s41523-018-0090-6 DO - 10.1038/s41523-018-0090-6 ID - Geyer2018 ER -