The HERA trial demonstrated survival benefits from the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy (ET) in premenopausal patients with hormone receptor (HR)-positive/HER2-positive early breast cancer. OFS combined with tamoxifen (TAM) over TAM alone following neoadjuvant chemotherapy is of unclear benefit, particularly in patients achieving pathologic complete response (pCR), a marker for improved disease-free survival (DFS) and overall survival (OS). This retrospective study evaluates the real-world impact of de-escalated ET in this setting.
A retrospective analysis was conducted on premenopausal patients aged ≤50 years with HR-positive/HER2-positive stage I to III breast cancer who achieved pCR (ypTis/T0 ypN0) after neoadjuvant chemotherapy at Memorial Sloan Kettering Cancer Center between 2008 and 2025. Patients were classified into 2 groups based on adjuvant ET: OFS combined with TAM or an aromatase inhibitor (AI) versus TAM alone. Patients receiving more than 1 type of ET were assigned to the group reflecting the therapy used for >75% of their total ET duration. Primary endpoints included DFS and OS, which were estimated using the Kaplan-Meier method and compared using log-rank tests. Patient characteristics were assessed with chi-square and Fisher’s exact tests, and univariable and multivariable Cox proportional hazards models were used to examine associations among patient characteristics, ET groups, and outcomes.
The study included 157 patients, with 67 receiving OFS plus TAM/AI and 90 receiving TAM alone. Median follow-up was 58.6 months (interquartile range, 41-79 months). At baseline, the OFS group had a higher prevalence of nodal involvement (67% vs 48%; P=.019) and high-grade tumors (82% vs 67%; P=.041) compared with the TAM group. Most patients underwent neoadjuvant chemotherapy with AC-THP regimens (75% vs 74%; P=.072), followed by adjuvant dual HER2 blockade (96% vs 92%; P=.8). The 5-year DFS was 97% (95% confidence interval [CI]: 92-100%); in the OFS group versus 89% (95% CI, 83-97) in the TAM group (P=.12). Multivariable analysis indicated that TAM alone was associated with a trend toward inferior DFS (hazard ratio, 3.44; 95% CI, 0.71-16.6; P=.12), whereas clinical stage III was significantly associated with worse DFS (hazard ratio, 4.71; 95% CI, 1.34-16.6; P=.016). No significant differences in OS were observed between groups (P=.9). Sensitivity analysis in 138 patients without ET switching yielded similar results.
In premenopausal patients with HR-positive/HER2-positive breast cancer achieving pCR after neoadjuvant chemotherapy, adjuvant OFS combined with TAM or an AI showed a trend toward improved DFS compared with TAM alone, although statistical significance was not reached, likely due to limited sample size. Patients with stage III disease remained at a higher risk for recurrence despite achieving pCR, suggesting they may benefit from intensified ET. Further studies are warranted to confirm these findings and refine treatment strategies for this high-risk subgroup.
Source: Modi S, Blotta DA, Mai N. Adjuvant ovarian function suppression (OFS) in HR+/HER2+ premenopausal breast cancer (BC) patients with pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC): a real-world study. Presented at: ESMO Congress 2025. October 20, 2025; Berlin, Germany. Abstract 433eP.