Abstract
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.
Highlights
The prospective-retrospective NSABP B-20 trial evaluating the Oncotype DX® 21-gene assay as a predictor of benefit from adjuvant chemotherapy in node-negative, estrogen-receptor (ER)-positive breast cancer demonstrated that a high recurrence score (RS), defined as 31 or higher, was predictive of chemotherapy benefit.[1,2] In preparation for the TAILORx trial, the analysis of the B-20 trial was repeated with the cutoffs employed in TAILORx: 25, and demonstrated that the patients with RS > 25 had a large benefit from the addition of chemotherapy.[3]
We report here for the first time results of an exploratory reanalysis of chemotherapy benefit in B-20 when excluding the cohort of patients with quantitative RT-PCR ≥ 11.5 units, in order to demonstrate the performance of the assay in predicting chemotherapy benefit for patients with node-negative, ERpositive, HER2-negative disease
Following publication of the results of the original analysis of the 21-gene assay as a predictive biomarker for chemotherapy benefit in NSABP B-20,1 expert panels recommended the assay for clinical use to determine potential benefit from the addition of chemotherapy to endocrine therapy in patients with ER-positive, HER2-negative, node-negative breast cancer.[9,10]
Summary
The prospective-retrospective NSABP B-20 trial evaluating the Oncotype DX® 21-gene assay as a predictor of benefit from adjuvant chemotherapy in node-negative, estrogen-receptor (ER)-. Positive breast cancer demonstrated that a high recurrence score (RS), defined as 31 or higher, was predictive of chemotherapy benefit.[1,2] In preparation for the TAILORx trial, the analysis of the B-20 trial was repeated with the cutoffs employed in TAILORx: 25, and demonstrated that the patients with RS > 25 had a large benefit from the addition of chemotherapy.[3] Supportive findings of chemotherapy benefit in patients with RS ≥ 31 were subsequently demonstrated in a similar prospective-retrospective analysis of SWOG-8814, conducted in patients with node-positive, ER-positive breast cancer.[4]. The 21-gene assay is based on RT-PCR analysis and integration of expression of 16 breast cancer-related genes and 5 reference genes.[5] HER2 is one of the genes in the RS algorithm with a positive coefficient and contributes to a higher RS value. In NSABP B-20, patients were accrued from October 1988 to March 1993, prior to establishment of routine clinical testing for HER2, so a portion of the patients accrued to B-20 were likely to have had HER2-positive disease.[6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
