Application of a neoadjuvant 21-gene breast recurrence score assay to redirect surgical and systemic treatment pathways in early breast cancer: A multicenter prospective study.

Abstract

596 Background: The 21-gene Oncotype DX Breast Recurrence Score assay is well established for determining use of adjuvant chemotherapy in hormone receptor (HR)-positive, HER2-negative breast cancer patients. However, the role of the 21-gene assay in the neoadjuvant setting has yet to be established. We previously reported the impact of the 21-gene assay in the neoadjuvant setting in node-negative breast cancer patients, which led to a reduction in the recommendation of chemotherapy in about one-third of patients. Here, we report the impact of the assay on neoadjuvant treatment pathways including surgery, endocrine therapy, and chemotherapy, in addition to overall costs. Methods: We performed a multicentre, prospective observational trial of HR-positive, HER2-negative breast cancer patients with T2-T3 disease and clinically negative axillary lymph nodes. Physicians completed questionnaires prior to and after Recurrence Score (RS) results, indicating their treatment choice for neoadjuvant endocrine or chemotherapy, or upfront surgery. Data was also collected at 6 months after initiation of therapy, to verify treatment received. The primary and secondary objectives were to evaluate impact of RS results on physician’s treatment decisions and on drug (anti-emetics and pre-medication), and nursing (counselling and infusion time) costs, respectively. Results: A total of 70 patients were enrolled in the study as part of five hospital centers of the McPeak Sirois Group in the province of Quebec from 2018-2021. Feasibility of the 21-gene assay from core biopsy samples was 98.6%. At 6-month follow-up, the 21-gene assay led to a change in treatment decision in 52.2% of patients, including de-escalation from neoadjuvant chemotherapy to either upfront surgery in 21.7%, or to neoadjuvant endocrine therapy in a further 21.7%. The use of upfront surgery changed from 10.0% at baseline to 33.3% at 6-month follow-up ( p = 0.0004). Use of neoadjuvant endocrine therapy also changed from 12.9% to 29.0% ( p = 0.02). Among patients treated with upfront surgery or neoadjuvant endocrine therapy, 52.2% and 55.0% of patients, respectively, had a RS≥16. At baseline, for all patients, total chemotherapy-associated drug costs were $190,656 CAD, and nursing-associated costs were $96,918 CAD. RS-guided treatment recommendation reduced chemotherapy-associated drug costs by 32.3% and nursing resource utilization by 44.1%. Conclusions: The use of the 21-gene assay reclassified treatment pathways in 52.2% of patients, including shifting patients from neoadjuvant chemotherapy toward upfront surgery or neoadjuvant endocrine therapy, while reducing chemotherapy-related resource utilisation. These data support the use of the 21-gene assay as a clinical decision-making tool in the neoadjuvant setting. Additional information: Coauthor André Robidoux, MD, died in July 2020.