Using Oncotype DX Breast Recurrence Score (R) (RS) assay to define the role of neoadjuvant endocrine therapy (NET) in early-stage hormone receptor positive (HR plus ) breast cancer (BC)

Abstract Background:Adjuvant endocrine therapy remains the standard of care for patients (pts) with early stage, HR+ BC who can safely omit chemotherapy based on RS results; however, the role of NET remains unclear. There are limited data regarding the optimal duration of treatment with NET and the ideal patient (pt) population for NET in terms of age and RS result. This question rose to critical importance amidst the COVID-19 pandemic, during which NET was utilized more broadly in attempts to delay surgery or chemotherapy while preserving optimal pt outcomes. This study re-examines the use of NET among a cohort of pts with HR+ BC randomized to NET or neoadjuvant chemotherapy (NCT) based on RS (performed on initial core biopsy specimens).Methods:Data were pooled from two independent studies performed at Emory’s Winship Cancer Institute and Massey Cancer Center at Virginia Commonwealth University (VCU) from 2010-2012. These studies evaluated rates of clinical and pathologic complete response (pCR) among pts with early stage, HR+ BC assigned to treatment groups based on RS results. Pts with RS 0-10 received NET (Group (Grp) A), RS 11-24/25 (Emory 11-24 vs VCU 11-25) were randomized to NET (Grp B) or NCT (Grp C), and those with RS 25/26-100 received NCT (Grp D). Associations between RS result, neoadjuvant therapy and pCR in the breast, lymph nodes (LN) and breast plus LN were evaluated using Fisher’s exact test. Results:109 pts were included in this analysis. The Emory cohort was younger (median age 56 years (yrs) vs 63 yrs in VCU cohort) and more diverse (37.5% African American (AA) vs 18.6% AA in VCU cohort). The pts were predominantly post-menopausal (69.6% Emory vs 83.1% VCU). Nodal status among the Emory cohort was evenly divided with 50% N0 and 50% N+, while the majority of VCU pts were N0 (76.3% N0 vs 22.0% N+). Pts were grouped based on RS result: RS <11 (18% Emory vs 20.3% VCU), RS 11-24/25 (36% Emory vs 55.9% VCU) and RS 24/25 or higher (46% Emory vs 23.7% VCU). Pts with low RS result were older (median 64 yrs vs 59 yrs among RS > 24/25) with higher percentage of low-grade tumors (47.6% grade 1 vs 5.4% grade 1 among RS >24/25). With regard to pCR, there were no significant differences among pts with low or intermediate RS results, as no pts in these groups achieved pCR in the breast or breast + LN (Table). Pts with RS result 25/26-100 (Grp D) were the only pts shown to achieve pCR in breast + LN (18.9%, p= 0.0043 across groups). Notably, while pts on the Emory study received longer courses of NET (median 10 months vs 5.5 months), there were no significant differences in pCR across RS result subgroups noted between the two institutions. Conclusion:Our results demonstrate that the use of Oncotype DX Breast Recurrence Score® or other genomic assays in the neoadjuvant setting may help guide treatment decisions when considering the use of NET versus NCT. Pt age and length of endocrine therapy as well as pt preferences should be considered when determining neoadjuvant treatment plans. There are currently ongoing studies evaluating the use of NET with CDK4/6 inhibitors that will offer further insight into optimal neoadjuvant treatment strategies in HR+ BC. Subsequent phase III evaluation of the role of genomic assays in the neoadjuvant setting is feasible and may help determine whether NET + CDK 4/6 inhibitors could replace NCT for pts with higher RS values. Table: pCR according to treatment groups (All Eligible Patients)VariableGroup A (N=21)Group B (N=23)Group C (N=22)Group D (N=37)P value (a)pCR Breast0 (0.0%)0 (0.0%)0 (0.0%)8 (21.6%)0.0016pCR Nodes0 (0.0%)1 (4.3%)3 (13.6%)2 (5.6%)0.2977pCR Breast + Nodes0 (0.0%)0 (0.0%)0 (0.0%)7 (18.9%)0.0043(a) Fisher's exact test was used for categorical variables with cell counts <5.Note: Group A= Recurrence Score <11,Group B= Recurrence Score 11-24 (Emory study) or 11-25 (VCUstudy) receiving NET,Group C= Recurrence Score 11-24 (Emory study) or 11-25 (VCUstudy) receiving NCT,and Group D= Recurrence Score >24 (Emory study) or >25 (VCUstudy).Note: 1 patient did not receive SLNB(sentinel lymph node biopsy) or ALND (axillary lymph node dissection) and is excluded from the denominator for pCR Nodes. Citation Format: Caitlin Taylor, Aimee Foreman, Christy Russell, Dipankar Bandyopdhyay, Xiaoyan Deng, Lisa Floyd, Amelia Zelnak, Ruth O'Regan, Harry Bear, Jane Meisel. Using Oncotype DX Breast Recurrence Score® (RS) assay to define the role of neoadjuvant endocrine therapy (NET) in early-stage hormone receptor positive (HR+) breast cancer (BC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-15-02.