Prognostic factors and the role of GnRHa in premenopausal HR+/HER2+ breast cancer achieving pathologic complete response after neoadjuvant chemotherapy.

BACKGROUND

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) generally have favorable outcomes. However, in the hormone receptor-positive/HER2-positive (HR+/HER2+) subtype, prognostic heterogeneity may persist even after pCR. In particular, the role of gonadotropin-releasing hormone agonist (GnRHa) for ovarian function suppression in premenopausal patients remains unclear. We aimed to identify prognostic factors and evaluate the clinical impact of GnRHa in this population.

METHODS

We performed a retrospective analysis of prospectively collected cohorts from Samsung Medical Center and Asan Medical Center. A total of 332 premenopausal patients with HR+/HER2+ breast cancer who achieved pCR after anti-HER2 containing NAC (2008 - 2021) were included. Patients were categorized according to GnRHa use during adjuvant endocrine therapy. The primary endpoints were disease-free survival (DFS) and distant metastasis-free survival (DMFS), analyzed using Cox proportional hazards regression and the Kaplan-Meier method.

RESULTS

Among 332 patients, 218 (65.7%) did not receive GnRHa and 114 (34.3%) did. With a median follow-up of 65.8 months, clinical nodal stage (cN3) was identified as an independent adverse prognostic factor for both DFS (HR 5.92, p < 0.001) and DMFS (HR 13.60, p < 0.001). In contrast, GnRHa use was not significantly associated with survival outcomes. Patients with cN3 disease showed significantly worse outcomes than those with cN0-2 (5-year DFS: 80.0%% vs 96.2%; DMFS: 87.5% vs 97.9%). No clear survival differences were observed according to GnRHa use. Subgroup analyses showed no significant association between GnRHa and survival, although a trend toward improved outcomes was observed in the cN3 subgroup.

CONCLUSION

Prognostic heterogeneity persists among premenopausal HR+/HER2+ patients achieving pCR, with baseline nodal status as a key determinant of outcomes. GnRHa was not associated with improved survival overall, although a potential benefit in high-risk subgroups cannot be excluded. These findings support a risk-adapted approach to adjuvant endocrine therapy rather than uniform intensification.