Background: The introduction of skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) with immediate reconstruction allowed a noticeable improvement in reconstructive surgery aesthetic results and patients' psychophysical well-being. In any case, there are still concerns about the long-term oncological safety of these two procedures. This study aims to assess the oncological outcomes of women who underwent SSM and NSM and to compare them with traditional modified total mastectomy (MTM). The secondary outcome was to compare mastectomy with breast-conserving surgery (BCS) outcome. Methods: We performed a retrospective chart review study concerning all patients who had experienced SSM and NSM in our Clinic between January 2004 and July 2013. The main outcomes were overall survival (OS), disease-free survival (DFS), and recurrences cumulative rate. Results: Among this study's 1836 invasive breast carcinomas, we found NSM (86.7, 95% confidence interval (CI), 76.7-98.0%) to have a significantly shorter 5-year DFS than MTM (90.4%, 95% CI, 87.9-93.0%). Furthermore, low body mass index (odds ratio (OR) 0.733, p = 0.056), basal-like molecular subtype (OR 28.932, p < 0.05), extended intraductal component (OR 11.160, p = 0.107), and lymph node metastasis extracapsular invasion (OR 8.727, p = 0.077) were the most significant predictors of recurrence in women treated with NSM. Furthermore, patients with BCS had significantly longer OS and DFS than those who underwent MTM. Conclusions: Occult nipple neoplastic involvement following negative intraoperative histological examination of subareolar tissue may explain the higher recurrence rate among women undergoing NSM. Patients with one or more risk factors for recurrence after NSM, such as basal-like molecular subtype, extended intraductal component, and extracapsular invasion of lymph node metastasis, should be given special attention.
