Abstract Background: Women with locally advanced triple negative breast cancer (LA-TNBC) have a high risk of disease recurrence and are monitored clinically and with annual mammograms. High risk women, such as BRCA1/2 carriers, are additionally monitored for second primary breast cancers (BC) with annual MRIs and may opt for risk reducing mastectomy (RRM) as a prophylactic measure. Our aim was to explore the clinical outcomes of patients (pts) with average BC risk and high BC risk (known BRCA1/2 carriers) who undergo RRM at the time of LA-TNBC diagnosis. Methods: We included 78 consecutive LA-TNBC pts, stages IIB and III, with resectable unilateral disease, treated at the Sunnybrook Health Sciences Centre from 2009 to 2018. Pts who did not undergo systemic chemotherapy and surgical treatment were excluded, as well as pts with a history of prior BC. Medical records were reviewed for clinical outcomes, pathology and germline BRCA1/2 testing results. Log rank test was used to determine the time to recurrence (TTR) and overall survival (OS) differences among women who underwent RRM and those who did not. Results: Median age at diagnosis of LA-TNBC was 49 years (range 27-82) and 14 (18%) pts were BRCA1/2 carriers. All pts underwent neoadjuvant chemotherapy with 27 (35%) presenting complete pathological response. Fifteen pts underwent RRM, out of which seven were BRCA1/2 carriers. Mean follow up time was 34 (2-86) months, during which 25 pts (32%) were diagnosed with distant disease recurrence and none with second primary BC. Median TTR was 10 months (range 1-48) and median OS was 18 months (range 2-86). RRM was not associated with TTR (p=0.45) and OS (p=0.98). Presence of germline BRCA1/2 also did not correlate with TTR (p=0.16) and OS (p=0.21). Conclusions: In our cohort of pts with LA-TNBC, the prognosis was driven by the risk of recurrence rather than the risk of second primary BCs. RRM was not associated with improved clinical outcomes, regardless the BRCA1/2 status and larger studies are required to support this procedure at the time of diagnosis of LA-TNBC. Citation Format: Neda Stjepanovic, Danilo Giffoni, Sonal Gandhi, Katarzyna Jerzak, Sharon Lemon, Karen Ott, Rossanna Pezo, Kathleen Pritchard, Samuel Tabbarah, Maureen Trudeau, Ellen Warner, William Tran, Andrea Eisen. Risk reducing mastectomy in average and high risk patients with locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-08.