Oncologic Trends, Outcomes, and Risk Factors for Locoregional Recurrence: An Analysis of Tumor-to-Nipple Distance and Critical Factors in Therapeutic Nipple-Sparing Mastectomy
Jordan D. Frey, M.D., Ara A. Salibian, M.D., Jiyon Lee, M.D., Kristin Harris, D.O., Deborah M. Axelrod, M.D., Amber A. Guth, M.D., Richard L. Shapiro, M.D., Freya R. Schnabel, M.D., Nolan S. Karp, M.D., Mihye Choi, M.D..
NYU Langone Health, New York, NY, USA.
Oncologic outcomes with nipple-sparing mastectomy (NSM) continue to be established. We examine oncologic trends and outcomes, including an analysis of tumor-to-nipple distance, in NSMs undertaken for therapeutic indications while also evaluating for risk factors for cancer recurrence.
Demographics, outcomes, and overall trends for all NSMs undertaken for therapeutic indications from 2006 to 2017 were reviewed. A univariate analysis was performed to identify independent risk factors for cancer recurrence in these cases. p-Values <0.05 were deemed significant.
A total of 496 therapeutic NSMs were performed during the study period. Average follow-up time was 48.25 months. The most common histologic tumor type was invasive carcinoma (52.4%) followed by ductal carcinoma in situ (50.4%). Average tumor size was 1.48 centimeters. In all, 25.2% of NSMs had multifocal disease while 11.5% had lymphovascular invasion. Of all NSMs, 59.9% were estrogen receptor-positive, 56.3% were progesterone receptor-positive, and 42.5% were HER 2-neu positive. Sentinel lymph node sampling was performed in 79.8% of NSMs; 4.1% had positive frozen sentinel lymph node biopsies while 15.7% had positive nodes on permanent examination. Rates of positive frozen and permanent subareolar biopsy results were 6.4% and 6.7%, respectively. The most common pathologic cancer stage was stage IA (42.5%) followed by Stage 0 (31.3%).
Per NSM, the rate of local in breast recurrence was 1.6% (N=8) while the rate of regional recurrence was 0.6% (N=3). Per patient, rates of local and regional recurrence were 2.6% and 1.0%. Four patients (1.3%) experienced distant metastasis. In all, 171 NSMs had magnetic resonance imaging available to assess tumor-to-nipple distance (TND). The average overall TND was 4.78 centimeters. TND did not significantly differ between NSMs with and without locoregional recurrence (4.62 versus 4.78 centimeters; p=0.8758). However, NSMs with TND ≤1 centimeter (25.0% versus 2.4%, p=0.0031) and ≤2 centimeters (8.7% versus 2.0%; p=0.0218) were significantly associated with higher rates of locoregional recurrence.
In univariate analysis, demographic-, operative-, and tumor-specific variables were examined to determine independent risk factors for locoregional recurrence. TND ≤1 centimeter was the only significant risk factor for recurrence (OR=13.5833, p=0.0385). Age <50 years (p=0.0503) and multifocal disease (p=0.0820), TND ≤2 centimeters (p=0.1052), and positive permanent subareolar biopsy (p=0.1094) trended towards being associated with higher risk of recurrence.
Nipple-sparing mastectomy represents an oncologically safe procedure with a locoregional recurrence rate of 2.0% in appropriately selected patients. Tumor-to-nipple distances of ≤1 centimeter was a significant predictor of locoregional recurrence on univariate analysis.
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