Is Mastectomy Necessary in Patients with Occult Breast Cancer and Advanced (N2/N3) Nodal Disease?

BACKGROUND/PURPOSE: Optimal surgical management of occult breast cancer (OBC) with N2/N3 nodal disease remains uncertain, but current National Comprehensive Cancer Network guidelines recommend mastectomy. We aimed to evaluate whether oncologic outcomes differ by local therapy. PATIENTS AND METHODS: We conducted an observational cohort study of patients with cT0N1-3M0 OBC treated at our institution between 2010 and 2025. We also analyzed data from patients registered in the National Cancer Database (NCDB) from 2006 to 2022. All patients included underwent neoadjuvant systemic therapy. Overall survival (OS) was estimated using Kaplan-Meier methods. RESULTS: Among 85 patients treated at our institution, 42 (49.4%) had cN1 disease, 15 (17.6%) had cN2 disease, and 28 (32.9%) had cN3 disease. A total of 14 (16.5%) underwent mastectomy. Over a median follow-up of 3.6 years [IQR: 1.8, 7.9], no in-breast or chest wall recurrences occurred. The 5-year OS and disease-free survival (DFS) were similar among patients undergoing whole-breast radiation versus mastectomy, regardless of nodal status. The NCDB analysis included 632 patients, of whom 558 (88.3%) underwent mastectomy and 74 (11.7%) had radiation without breast surgery. For patients with cN2/N3 disease, 5-year OS was 96.3% (95% CI: 77.7-99.9%) with whole-breast radiation versus 84.3% (95% CI: 78.3-89.0%) with mastectomy. CONCLUSIONS: There is not strong evidence for improved local control or survival with mastectomy in patients with OBC, even among those with advanced nodal disease. This lack of evidentiary support should be discussed in shared decision-making when mastectomy is presented as the default recommendation for all patients with OBC and N2/N3 disease.