The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians Already Decided?

Abstract

Background: The 21-gene recurrence score (RS) assay is retrospectively validated for assessing prognosis and benefit from chemotherapy in hormone receptor-positive, early-stage breast cancer (EBC) with low RS. We hypothesized that oncologists have already incorporated the RS assay for decision-making in higher-risk, node-positive disease, despite the lack of prospective data and contrary to NCCN Guideline recommendations. This study provides the first analysis of trends and differences in RS use and therapeutic implications in a population-based data set of patients with node-positive EBC. It also assesses the impact of the RxPONDER trial on clinicians' chemotherapy recommendations. Methods: Node-positive EBC cases diagnosed during 2010 through 2012 and included in the National Cancer Data Base were used. Multivariate logistic regression was used to estimate test use and impact on chemotherapy recommendations. Results: The RS assay was ordered for 16.5% of the 80,405 identified patients. Of all variables, the RS assay had the strongest association with chemotherapy recommendation, with adjusted odds ratios (AORs) of 19 for scores >30. Odds of chemotherapy recommendation were significantly lower for the group who received the test (AOR, 0.21; 95% CI, 0.20-0.22). When divided based on the cutoff point of 25 adopted by the RxPONDER trial, those with an RS of 18 to 25 had significantly lower odds of chemotherapy recommendation compared with those with an RS of 26 to 30 (AOR, 0.32; 95% CI, 0.26-0.40). Test use was lower for blacks, community centers, uninsured/governmentally insured patients, higher tumor grade, larger tumor size, and more nodes involved. Chemotherapy recommendation was higher for patients of younger age, with private insurance, and with higher tumor grade, size, and number of nodes involved. Black patients had significantly higher RS (AOR, 1.37; 95% CI, 1.25-1.79). Conclusions: The RS assay influences clinicians' chemotherapy recommendation in node-positive EBC. Clinicians are using the inclusion criteria of the RxPONDER trial before its final release. Black patients have higher RS, likely representing worse biology. Significant differences exist in test use and clinical implications based on race, insurance, and facility.

Ki‐67 index, progesterone receptor expression, histologic grade and tumor size in predicting breast cancer recurrence risk: A consecutive cohort study

“…For HR‐positive EBC patients, the predictive advantage of the IHC3 model needs to be confirmed by longer follow‐up. Lastly, patients with metastasized lymph nodes, ER‐positive breast cancer were not enrolled in this study because although the 21‐gene RS has been demonstrated to be a predictor of the benefit of chemotherapy for such patients [32], the NCCN guidelines before 2018 recommend chemotherapy for these patients without the need for the 21‐gene assay.…”

Factors Determining Anthracycline Use in Hormone Receptor Positive, Early-Stage Breast Cancer

“…Controversy, however, exists as to the utility of the 21-gene assay in lymph node-positive disease. 12 There is currently no prospective data for lymph node-positive disease; however, retrospective analysis of the SWOG (Southwestern Oncology Group)-8814 suggests node-positive patients with a low recurrence score do not seem to benefit from adjuvant chemotherapy. 13 A descriptive study from the University of Michigan in 2016 reported that many physicians use the recurrence score to guide chemotherapy selection, despite the lack of evidence supporting its use in this manner.…”

Adjuvant Systemic Treatment in Hormone Receptor Positive, HER2 Negative Breast Cancer

“…Rx for Positive Node, Endocrine Responsive Breast Cancer (RxPONDER) trial is an ongoing multicenter phase III trial revealed that patients with node positive breast cancer who had low to intermediate RS results could benefit from chemotherapy [13]. The trial also determined whether there is an optimal RS cutoff for these patients above which chemotherapy should be recommended in clinical practice.…”