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Original Investigation
August 28, 2019

Breast Cancer Recurrence in the Nipple-Areola Complex After Nipple-Sparing Mastectomy With Immediate Breast Reconstruction for Invasive Breast Cancer

Author Affiliations
  • 1Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea
  • 2Department of Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China
  • 3Department of Plastic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea
  • 4Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea
  • 5Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea
  • 6Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea
JAMA Surg. Published online August 28, 2019. doi:10.1001/jamasurg.2019.2959
Key Points

Question  What are the incidence of and risk factors and long-term outcomes associated with breast cancer recurrence at the nipple-areola complex after nipple-sparing mastectomy for invasive breast cancer?

Findings  In this cohort study of 962 breasts from 944 patients who underwent nipple-sparing mastectomy and immediate breast reconstruction for invasive breast cancer, 39 cases of cancer recurrence at the nipple-areola complex were identified as the first event; multifocality or multicentricity, negative hormone receptor and ERBB2 (formerly HER2 or HER2/neu)–positive subtype, high histologic grade, and extensive intraductal component were independently associated with recurrence. Patients with and without recurrence of cancer at the nipple-areola complex as the first event did not differ significantly with regard to distant metastasis-free or overall survival.

Meaning  The findings suggest that biological features of the breast cancer tumor should be considered when planning nipple-sparing mastectomy.

Abstract

Importance  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.

Objective  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.

Design, Setting, and Participants  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.

Main Outcomes and Measures  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.

Results  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.

Conclusions and Relevance  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.

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