Use of 21-gene recurrence score assay to individualize adjuvant chemotherapy recommendations in ER+/HER2\u2212 node positive breast cancer\u2014A National Cancer Database study

Prema P Peethambaram,Elizabeth B Habermann,Matthew P Goetz,Judy C Boughey,Tanya L Hoskin,Courtney N Day

doi:10.1038/s41523-017-0044-4

Prema P Peethambaram, Elizabeth B Habermann + Show 4 more

Open Access

https://doi.org/10.1038/s41523-017-0044-4

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Journal: npj Breast Cancer	Publication Date: Oct 19, 2017
Citations: 18	License type: open-access

Affiliation: Mayo Clinic, Winneshiek Medical Center

Abstract

The 21-gene Recurrence Score (RS) assay is prognostic and predictive of adjuvant chemotherapy benefit in node positive (N+) breast cancer (BC). We sought to evaluate use patterns of RS assay in N+, ER+/HER2− BC and the impact of RS on recommendations for adjuvant chemotherapy. Patients with T1-T4c,N1mi-N3, ER+/HER2− BC diagnosed 2010–2013 in the National Cancer Database were analyzed. Multivariable logistic regression assessed factors influencing RS testing and chemotherapy recommendations based on RS. Among 72,897 patients, RS was obtained in 20.6%, increasing from 15.0% in 2010 to 24.5% in 2013 (p < 0.001). RS testing was most common in N1mi (43.7%) followed by N1 (22.1%) and rare in N2/N3 (3.3%). Of the 12,536 with quantitative RS results, 61.1% were low RS, 32.3% intermediate RS and 6.6% high RS. Chemotherapy was recommended less frequently in patients with RS testing (50.4%) vs. those not tested (81.0%, p < 0.001). In N1mi/N1 patients, chemotherapy recommendation varied by RS; however, in N2/N3 patients, chemotherapy was recommended in the majority (70.9–87.5%) regardless of RS. Most patients (>85%) with RS ≥ 26 were recommended chemotherapy regardless of nodal stage. For patients with RS < 26, chemotherapy recommendations increased with higher N and T stage, grade, and younger age (p < 0.001). Histology was not associated with chemotherapy recommendation in any RS subset. The RS assay is frequently and increasingly being used for decision making in node positive ER+/HER2− breast cancer patients and its use is associated with lower rates of adjuvant chemotherapy.

Highlights

For the treatment of estrogen receptor (ER) positive breast cancer, adjuvant endocrine therapy provides the greatest benefit in terms of reduction in distant recurrence and breast cancer mortality
Recurrence Score (RS) testing was more commonly obtained in patients who had private insurance/managed care (21.7%) or Medicare (20.6%), than among those with Medicaid or no insurance (15.1%, p < 0.001)
Chemotherapy is standardly recommended for ER+, node positive breast cancer based on a meta-analysis of multiple prospective clinical studies demonstrating that poly-chemotherapy significantly reduces breast cancer mortality for ER+, node positive breast cancer.[5]

Summary

Introduction

For the treatment of estrogen receptor (ER) positive breast cancer, adjuvant endocrine therapy provides the greatest benefit in terms of reduction in distant recurrence and breast cancer mortality. The 21 gene recurrence score (RS)[6,16] has been determined to be prognostic in both node negative and node positive ER+/HER2− breast cancer.[16,17,18,19,20] the RS has been studied in secondary analysis of prospective clinical trials which tested the benefit of adjuvant chemotherapy and provides limited evidence that RS is predictive of chemotherapy benefit in node positive ER+/HER2− breast cancer patients.[17,18,19,20,21,22] Based on these studies, NCCN guidelines recommends the use of the RS in decision making in the setting of both node negative and node positive (1–3 lymph nodes) ER+ breast cancer. While prospective clinical trials are ongoing to answer this question, these disparate recommendations may lead to confusion among patients and providers and impact reimbursement by payers.[22]

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