Background: Meta-analyses have demonstrated that young women ≤40 (YW) derive the most benefit from chemotherapy (EBCTCG, Lancet. 1998). Oncotype DX was designed to determine the benefit of chemotherapy in women with ER+/HER2-, node-negative (LN-) breast cancer based on recurrence score (RS). TAILORx reported clinically meaningful benefits in freedom-from-distant recurrence in women <50 with the addition of chemotherapy to endocrine therapy when RS was 16-25. Recent TAILORx analyses suggest that women <40 with an intermediate (int) RS do not derive chemotherapy benefit, though YW comprised <4% of the trial population . Defining the optimal adjuvant treatment strategy for this population of YW remains a clinical challenge. We sought to determine national patterns of RS utilization in association with receipt of chemotherapy and to characterize the association of RS with tumor characteristics and demographics among YW with early stage ER+, LN- breast cancer.
Methods: Using the National Cancer Data Base (NCDB), we identified individuals age <75, diagnosed 2010-2015 with stage I-II, ER+/HER2-, LN- breast cancer with known RS. Cohorts were defined as low (0-10), int (11-25), and high (>25) RS. Age categories were classified as ≤40, 41-50, and >50. Chi-square tests or Fisher’s exact tests were used to compare categorical variables. Logistic regression was used to estimate the association of RS score and age group with adjuvant chemotherapy use, after adjustment for known covariates. Kaplan-Meier curves were used to visualize unadjusted overall survival (OS), and Cox proportional hazards models were used to estimate adjusted OS.
Results: 120,051 women were identified, of whom 4,781 were ≤40 years, 24,846 were 41-50, and 90,424 were >50. By age group, 20% of YW had a high RS compared to 12% of women age 41-50 and 15% of women >50 (p<0.001). Among YW, black women were more likely than white women to have a high RS; 29% vs. 19% (p<0.001). RS was strongly associated with receipt of chemotherapy in YW (86% of high RS vs. 33% of int RS vs. 7% of low RS, p<0.001). Chemotherapy was omitted in 55% of YW with RS 16-25. YW in multivariate analysis with a low or int RS were more likely than women 41-50 or >50 to receive chemotherapy (p<0.001). Receipt of chemotherapy for YW with an int RS was associated with younger chronologic age (p<0.001), ductal histology (p=0.02), high grade (p<0.001), and higher pathologic T-stage (p<0.001). Among YW, the unadjusted 5-year OS (95% CI) was as follows: low RS= 100% (0.99-1), int RS= 100% (1-1), high RS= 93% (0.90-0.96). Chemotherapy did not influence 5 year OS in YW with an int RS. In univariate analysis, a high RS was associated with a worse 5-year OS in YW (log-rank p<0.001). After adjustment for race and chemotherapy receipt, high vs. low RS was associated with an increased risk of death (HR=5.86, 95% CI 1.19-28.82, p=0.03) in YW.
Conclusions: High RS is more common in YW (≤40) than those age 41-50 or >50, and is associated with worse OS. YW with an int or low RS are more likely to receive chemotherapy despite unclear benefit. Chemotherapy was omitted in over half of YW with RS of 16-25, highlighting the uncertainty in clinical practice which will remain until further studies inform optimal systemic treatment specific to YW.
1. Sparano, J.A., et al., Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. New England Journal of Medicine, 2019. 380(25): p. 2395-2405.
Citation Format: Sarah Sammons, Yi Ren, Jeremy Force, Oluwadamilola M. Fayanju, Laura H. Rosenberger, Jennifer K. Plichta, Gretchen Kimmick, Kelly Westbrook, Susan Dent, Carey Anders, Samantha M. Thomas, Terry Hyslop, E. S. Hwang, P. K. Marcom, Rachel A. Greenup. Characterization of oncotype DX recurrence score and chemotherapy utilization patterns in young women (≤40) with early stage ER+/HER-, lymph node negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-10.