Abstract P2-03-12: Impact of adjuvant endocrine therapy (ET) omission in ER+ breast cancer (BC) treated with neoadjuvant chemotherapy (NAC)
Authors: Choong Grace M. , Boughey Judy C. , Hoskin Tanya L. , Day Courtney N. , Goetz Matthew P. 
Published: March 2023

Abstract
Background: Adjuvant endocrine therapy (ET) in ER+ breast cancer (BC) reduces local, distant, and contralateral BC events and improves overall survival (OS). Furthermore, decreased adherence or omission of ET increases the risk of death. However, in ER+ pts with early-stage BC treated with NAC who have a pathologic complete response (pCR), the importance of adjuvant ET may be called into question. We sought to examine the impact of ET omission on the survival of pts with ER+ BC treated with NAC, according to pCR vs residual disease.
Methods: We queried the National Cancer Database (NCDB) 2010-2018 for female pts with stage I-III ER+ BC treated with NAC followed by surgery. pCR was defined as ypT0/ypTis, ypN0. The percent receiving adjuvant ET and the impact of adjuvant ET omission on overall survival (OS) in patients with and without pCR were assessed separately based on HER2 expression. OS was analyzed with adjuvant ET as a time-dependent covariate using Cox proportional hazards regression.
Results: We identified 34,394 pts treated with NAC for ER+ BC (28,434 ER+/HER2-, 5960 ER+/HER2+). Pts with ER+/HER2+ BC were less likely than pts with ER+/HER2- BC to have received adjuvant ET (61.6% vs 88.8%, p&lt; 0.001). Overall, 4505 (13.1%) had pCR (9.1% of ER+/HER2- and 32.0% of ER+/HER2+). Within each subtype, pts with pCR were significantly less likely to start adjuvant ET after surgery than pts with residual disease (78.4% vs 89.8% for ER+/HER2- and 46.5% vs 68.7% for ER+/HER2+, each p&lt; 0.001), Table 1. Regarding those with residual disease, pts with ER+/HER2+ BC were less likely than ER+/HER2- BC to receive adjuvant ET (68.7% vs 89.8%, p&lt; 0.001). Median follow-up was 4.4 years. Among pts with pCR, 5-year OS was 93.2% (95% CI: 92.1-94.4%) for ER+/HER2- BC and 94.3% (95% CI: 93.1-95.5%) for ER+/HER2+ BC (p=0.08), while among patients with residual disease 5-year OS was 81.7% (95% CI: 81.1-82.2%) and 85.7% (95% CI: 84.5-86.9%) for the two subtypes respectively (p&lt; 0.001). On multivariable analysis, omission of adjuvant ET was significantly associated with poorer OS in patients with residual disease for both ER+/HER2- BC (adjusted HR 1.72, p&lt; 0.001) and ER+/HER2+ BC (adjusted HR 1.63, p&lt; 0.001). In contrast, omission of adjuvant ET was not significantly associated with OS in patients with pCR, regardless of HER2 status (ER+/HER2- adjusted HR 1.28, p=0.20; ER+/HER2+ adjusted HR 1.13, p=0.54), Table 1.
Conclusions: In pts receiving NAC for ER+ BC, those with ER+/HER2+ disease were less likely to have received adjuvant ET compared to ER+/HER2- patients, regardless of pCR. In pts with residual disease after NAC, omission of adjuvant ET was associated with significantly higher risk of death. These data provide strong support for interventions to increase utilization of ET, especially for patients with residual disease following NAC. The observation that ET omission did not impact OS in pts with ER+ BC who achieve pCR following NAC is hypothesis generating and may have implications for future de-escalation trials for this subset of patients.
Table 1. Differential use of adjuvant endocrine therapy by subtype and pCR and the impact on overall survival
Citation Format: Grace M. Choong, Judy C. Boughey, Tanya L. Hoskin, Courtney N. Day, Matthew P. Goetz. Impact of adjuvant endocrine therapy (ET) omission in ER+ breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-12.