21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer - PubMed (original) (raw)

21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer

Charles E Geyer Jr et al. NPJ Breast Cancer. 2018.

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.

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Conflict of interest statement

Dr. Mamounas: Genomic Health, Inc.: Consultant, Honoraria (Speaker); Biotheranostics: Consultant. Dr. Paik discloses being listed as one of the inventors of OncotypeDx in the patents, but all rights have been transferred to NSABP Foundation, resulting in no financial interest. Dr. Shak: Genomic Health, Inc.: Full-time employee and shareholder. Dr. Crager: Employment at Genomic Health, Inc., and ownership of company stock. Dr. Baehner: Employee and minor shareholder of Genomic Health, Inc. All other authors declare no other potential competing interest(s).

Figures

Fig. 1

Fig. 1

CONSORT Diagram for 21-gene assay study using available primary breast cancer specimens from NSABP B-20

Fig. 2

Fig. 2

Kaplan–Meier estimates of the probability of remaining free of distant recurrence by original RS groups following exclusion of patients with presumed HER2-positive disease, comparing treatment with tamoxifen alone with tamoxifen plus chemotherapy. a All patients; b low-risk RS < 18; c intermediate-risk RS 18–30; and d high-risk RS ≥ 31

Fig. 3

Fig. 3

Kaplan–Meier estimates of the probability of remaining free of distant recurrence by TAILORx RS groups following exclusion of patients with presumed HER2-positive disease comparing treatment with tamoxifen alone with tamoxifen plus chemotherapy. a RS < 11; **b** RS 11–25; **c** RS > 25

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