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The main concern associated with nipple-sparing mastectomy (NSM) is the risk of local breast cancer recurrence at the retained nipple-areola complex (NAC) consequent to occult nipple involvement. Long-term follow-up data regarding the oncologic safety of modern therapeutic NSM in terms of cancer recurrence at the NAC and survival are limited.To assess the incidence, risk factors, treatment, and long-term outcomes associated with cancer recurrence at the NAC in a large series of patients with invasive breast cancer who underwent NSM and immediate breast reconstruction.In this retrospective cohort study at a single institution (Asan Medical Center) in Seoul, Republic of Korea, 962 breasts from 944 patients who underwent NSM and immediate breast reconstruction for invasive breast cancer were analyzed between March 3, 2003, and December 31, 2015. Patients who underwent neoadjuvant systemic therapy or palliative surgery were excluded. Data analysis was performed from June 4, 2018, to August 31, 2018.Univariate and multivariate Cox proportional hazards regression models were used to analyze the association between clinicopathologic variables and cancer recurrence at the NAC. To evaluate the association between cancer recurrence at the NAC and prognosis, distant metastasis-free survival, and overall survival were estimated using the Kaplan-Meier method and compared using the log-rank test.Among the 944 study patients (median age at diagnosis, 43 years [range, 23-67 years]) during a median follow-up of 85 months (range, 14–185 months), 39 cases (4.1%) of cancer recurrence at the NAC were identified as the first event after NSM. The 5-year cumulative incidence of cancer recurrence at the NAC was 3.5% (n = 34). In multivariate analyses, multifocality or multicentricity (hazard ratio [HR], 3.309; 95% CI, 1.501-7.294; P = .003), negative hormone receptor or ERBB2 (formerly HER2 or HER2/neu)–positive subtype (HR, 3.051; 95% CI, 1.194-7.796; P = .02), high histologic grade (HR, 2.641; 95% CI, 1.132-6.160; P = .03), and extensive intraductal component (HR, 3.338; 95% CI, 1.262-8.824; P = .02) were independently associated with cancer recurrence at the NAC after NSM. All 39 recurrent cases involved wide local excision. Patients with and without cancer recurrence at the NAC as the first event did not differ significantly with regard to distant metastasis-free survival (P = .95) or overall survival (P = .21). The 10-year distant metastasis-free survival rates were 89.3% among patients with cancer recurrence at the NAC and 94.3% among patients without recurrence. The 10-year overall survival rates were 100% among patients with cancer recurrence at the NAC and 94.5% among those without recurrence.Patients had a low incidence of cancer recurrence at the NAC after NSM and immediate breast reconstruction in this study. The findings suggest that multifocal or multicentric disease, hormone receptor–negative/ERBB2–positive subtype, high histologic grade, and positive extensive intraductal component should be considered before determining the NSM procedure.