Overall survival association of adjuvant endocrine therapy (ET) after pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in ER+/HER2+ early-stage breast cancer.

541 Background: In ER+/HER2+ early breast cancer, adjuvant ET is standard; however, its survival benefit for patients achieving pCR after NAC remains uncertain. As pCR is associated with favorable prognosis and may inform postoperative decision-making, it is unknown if pCR identifies a subset in whom the ET survival benefit is reduced. We evaluated ET use patterns and its association with overall survival (OS) in ER+/HER2+ patients with pCR after NAC. Methods: Using NCDB, we identified women with ER+/HER2+ M0 breast cancer treated with NAC and definitive surgery (2018-2022) who achieved pCR (ypT0/ypTis and ypN0). The primary endpoint was OS. To reduce immortal time bias, we used a time-varying Cox model with ET initiation as a time-dependent exposure (time zero: surgery). A 6-month landmark analysis was performed as a sensitivity analysis. Multivariable models adjusted for demographic, clinicopathologic, treatment, and socioeconomic variables. Predictors of ET omission were assessed using multivariable logistic regression. Exploratory analyses evaluated ER-low (1-10%) and effect modification using an ET×ER-low interaction term. Results: Of 8,981 patients, 7,917 (88.2%) received ET and 1,064 (11.8%) did not. In the time-varying Cox model, ET receipt was associated with improved OS (HR 0.79, 95% CI 0.67-0.93). Worse OS was associated with older age (per 10 years: HR 1.17, 95% CI 1.10-1.24) and stage III disease (HR 1.39, 95% CI 1.16-1.67). In 6-month landmark analysis (n=8,756), ET benefit persisted (HR 0.58, 95% CI 0.39-0.86). There was no differential association by ER-low status (ET×ER-low interaction p =0.73), with similar ET associations in ER-high (HR 0.58) and ER-low (HR 0.63) groups. ET was omitted in 36.9% of ER-low patients compared to only 7.6% of ER-high patients. Logistic regression identified ER-low status as the strongest predictor of ET omission (OR 0.16, 95% CI 0.14-0.19). Omission was also more likely with older age (per 10-year increase: OR 0.92, 95% CI 0.85-0.99) and community facility treatment (OR 0.74, 95% CI 0.55-0.99), while ET receipt was more likely with PR-positivity (OR 1.54, 95% CI 1.32-1.79), radiation (OR 2.78, 95% CI 2.32-3.33) and HER2-targeted therapy (OR 2.62, 95% CI 2.03-3.38). Conclusions: In this NCDB cohort, adjuvant ET was associated with improved OS in ER+/HER2+ patients achieving pCR after NAC. The survival association did not differ by ER-low status, though event rates in this subgroup were limited. ER-low status was the strongest predictor of ET omission, highlighting a potential gap between real-world practice and outcomes. These findings support continued consideration of ET in post-pCR ER+/HER2+ patients, including the ER-low population. Cohort Total N ET (%) No ET (%) Death (%) Overall 8,981 7,917 (88.2%) 1,064 (11.8%) 152 (1.7%) ER-low 1,316 831 (63.1%) 485 (36.9%) 32 (2.4%)