%0 Journal Article
%T 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer
%J -
%D 2018
%R https://doi.org/10.1038/s41523-018-0090-6
%X The NSABP B-20 prospective-retrospective study of the 21-gene Oncotype DX Breast Cancer Recurrence Scoreˋ 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每30, ≡31, and the TAILORx cutoffs: <11, 11每25, >25. The endpoint remained distant recurrence-free interval (DRFI) as in the original study. Distribution was estimated via the Kaplan每Meier method and compared via log-rank test. Multivariate Cox proportional hazards models estimated chemotherapy benefit in each group. In the RSˋ<ˋ18 and 18每30 groups, 1.7 and 6.7% were HER2 positive. In the RSˋ≡ˋ31 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 Pˋ=ˋ0.06), but substantial benefit from chemotherapy remained in the RSˋ≡ˋ31 cohort (HRˋ=ˋ0.18; 95% CI: 0.07每0.47) and the RSˋ>ˋ25 cohort (HRˋ=ˋ0.28; 95% CI: 0.12每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 RSˋ≡ˋ31 as originally employed, and with RSˋ>ˋ25 employed in TAILORx
%U https://www.nature.com/articles/s41523-018-0090-6