Abstract P5-09-07: Risk reducing strategy in germline BRCA mutated patients with locally advanced breast cancer. Establishing mastectomy as a preventing procedure of local recurrence
Authors: Tunon de Lara C , Leroux J , Bonnet F , Debled M , Barrouk-Simonet E , Quenel-Tueux N , Lagarde P , Chassaigne F , Esnaud T , Fournier M , Bubien V , Breton-Callu C , Charitansky H , Petit A , Mathoulin-Pelissier S , Macgrogan G , Longy M , Sevenet N 
Published: May 2019

Abstract
Introduction
Neoadjuvant chemotherapy (NAC) is proposed for locally advanced breast cancer (LABC) to increase the breast conservative treatment (BCT). In France, mastectomy is the risk-reducing prophylactic surgical strategy only for pre-symptomatic germline BRCA-mutated (gBRCAm) patients. On the other hand, BCT is proposed to all patients following NAC based on clinical response, regardless the gBRCAm status. The aim of this retrospective study is to evaluate the risk of local recurrence (LR) according to BRCA status.
Patients and methods
Inclusion criteria were: (i) patients treated for unilateral LABC, T2-3, N≥0, M0 by NAC, and (ii) patients who underwent germline BRCA screening. , using targeted next-generation screening, was carried out either during NAC (rapid process) or after surgery. Deleterious mutations were confirmed using Sanger sequencing before passing on the results to the clinical geneticist. Some gBRCAm patients from Olympia study were also included. Patients were followed-up over a long term for overall survival, LR and disease-free survival. Chi-square and Fischer test were used to generate statistical comparison.
Results
Between 2007 and 2015, 988 women were treated for LABC at our institution. Among them, 151 patients underwent clinical genetic testing for gBRCAm based on these criteria: young age at diagnosis or familial history of breast or ovarian cancer or histological characteristics as grade 2/3, Her2-3+ or basal like. A total of 122 patients were included in the study; 28 patients had gBRCAm status and no mutations were detected in 94 patients (wtBRCA). Significant differences between the two groups (gBRCAm vs wtBRCA) were observed for
Mean age, (36.7 vs 40.1y (p=0.0032) ,
Intrinsic tumor subtypes basal like (64.3% vs 42.5%, p=0.0432)
ER are more often negative (21.4% vs 46.8%, p=0.0165).
Among the 30 patients who underwent BRCA screening during NAC and eligible for BCT, 8 of the 9 patients with gBRCAm choose mastectomy (88%). Among the 92 patients with screening mutation after breast cancer treatment, 5 of the 19 patients with gBRCAm had a mastectomy (28%). In the 28 gBRCAm patients, 15 had a BCT and 13 a mastectomy. In the 94 wtBRCA patients, 67 had a BCT and 27 a mastectomy. After a follow-up of 4.32 years, we observed 8 relapses, 5 LRs after BCT and 3 contro-lateral relapses. Of the 5 LRs, 3 came from 15 gBRCAm with BCT and 2 of the 67 wtBRCA (p=0.0403).
Discussion
In this selected subgroup of patients, gBRCAm rate is higher (23%) than the rate based on familial criteria for BRCA testing (12%). Regarding the rationale for BCT or mastectomy procedure in LABC and pre-symptomatic gBRCAm patients, this study led us to establish mastectomy as risk-reducing strategy in a sole surgery procedure for gBRCAm patients. Moreover, 88% gBRCAm patients chose mastectomy; the mastectomy rate was lower when the patient was unaware of their BRCA status (26%). The LR rate was higher in the gBRCAm vs wtBRCA with a statistical difference. In LABC patients with high genetic risk, the knowledge of mutation status could influence patients' and surgeons' choice of surgery. In case of gBRCAm status, mastectomy is recommended to decrease LR risk.
Citation Format: Tunon de Lara C, Leroux J, Bonnet F, Debled M, Barrouk-Simonet E, Quenel-Tueux N, Lagarde P, Chassaigne F, Esnaud T, Fournier M, Bubien V, Breton-Callu C, Charitansky H, Petit A, Mathoulin-Pelissier S, Macgrogan G, Longy M, Sevenet N. Risk reducing strategy in germline BRCA mutated patients with locally advanced breast cancer. Establishing mastectomy as a preventing procedure of local recurrence [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-07.