Abstract PS3-01-14: Oncological and Surgical Outcomes of Risk Reducing Nipple Sparing Mastectomy in Germline Pathogenic Variant Carriers

Abstract Background: Nipple-sparing mastectomy (NSM) is increasingly adopted as a risk-reducing surgical approach in women with germline pathogenic variants (PVs). Although oncologic outcomes are well established for risk-reducing mastectomies in BRCA1/2 carriers, data are limited for NSM as well as for individuals with other high- and moderate-penetrance PVs. This study aimed to evaluate the incidence of new breast cancer, cosmetic outcomes and surgical complications following risk-reducing NSM in PV carriers. Methods: We conducted a multicenter retrospective cohort study of risk-reducing NSM performed between 2008 and 2025 across 12 institutions. Asymptomatic patients (bilateral risk-reducing mastectomy [BRRM]) or individuals with unilateral breast cancer (contralateral risk-reducing mastectomy [CRRM]) were included. Patients with occult malignancy detected at NSM were excluded. Crude incidence rates were used to report new breast cancer diagnoses and complications. Cosmetic outcomes were assessed using the Harvard four-point scale. Risk factors for complications were analyzed using univariable (UVA) and multivariable (MVA) analyses. Results: A total of 524 patients underwent risk-reducing NSM: 219 BRRM and 305 CRRM (743 mastectomies). Most patients carried BRCA1 (46.0%) or BRCA2 (25.4%) PVs, followed by TP53 (15.1%). Median age was 40 years (range 20-68). At a median follow-up of 41.2 months (IQR 13.1-60.3), three patients (0.6%) developed breast cancer: one nodal recurrence post-BRRM, and two flap recurrences post-CRRM (BRCA1 [n=2] and BRCA2 [n=1]). Breast cancer-related death occurred in three patients (0.6%), all following CRRM. Cosmetic outcomes were favorable, with 90% rated as excellent or good. Surgical complications occurred in 101 patients (19.3%), more frequently after CRRM (24.6%) than BRRM (11.9%) (p<.001). On UVA, complications in BRRM were associated with obesity (OR 9.15, 95% CI 2.08-40.2, p=0.003) and Wise-pattern incision (OR 35.0, 95% CI 2.57-47.3, p=0.008). In CRRM, comorbidities (OR 2.76, 95% CI 1.38-5.54, p=0.004) and Wise-pattern incision (OR 7.33, 95% CI 1.65-32.5, p=0.009) were significant. On MVA, comorbidities (OR 2.59, 95% CI 1.23-5.47, p=0.012) and Wise-pattern incision (OR 7.83, 95% CI 1.73-35.5, p=0.008) remained independently associated with complications in CRRM; no independent predictors were found in BRRM. Conclusion: In this multicenter cohort of women with high- and moderate-penetrance germline PVs, risk-reducing NSM was associated with a very low incidence of new breast cancer (0.6%), supporting its oncologic safety. Most patients achieved favorable cosmetic outcomes. Surgical complication rates were higher after CRRM and associated with comorbidities and Wise-pattern incisions. These findings may guide surgical planning and patient counseling for risk-reducing NSM in genetically predisposed populations. Citation Format: F. P. Cavalcante, M. Antonini, A. L. Frasson, I. de Oliveira-Junior, F. P. Brenelli, A. Berretini Junior, G. N. Garcia, F. Bagnoli, F. P. Zerwes, E. C. Millen, A. Mattar, J. P. Reis, R. Fenile, R. A. da Costa Vieira, H. R. de Oliveira Filho, M. Lichtenfels, R. Sandoval, P. L. Quidute, R. Z. Torresan, L. M. Zuliani, M. M. Bortoluzzi, A. D. Lima, R. S. Guindalini, N. Polidorio. Oncological and Surgical Outcomes of Risk Reducing Nipple Sparing Mastectomy in Germline Pathogenic Variant Carriers [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-14.