Abstract P5-16-23: Rapid germline BRCA screening for locally advanced breast cancer changes surgical procedure after neoadjuvant chemotherapy
Authors: Tunon de Lara C , Bonnet F , Debled M , Lafon D , Breton-Callu C , Rarouk-Simonet E , Fournier M , Petit A , Bubien V , Quenel-Tueux N , Lagarde P , Longy M , Macgrogan G , Sevenet N 
Published: May 2019

Abstract
Introduction
Neoadjuvant chemotherapy (NAC) is proposed in case of locally advanced breast cancer (LABC) to improve breast conservative treatment (BCT). In the case of germline BRCA mutated (gBRCAm) patients, risk-reducing prophylactic surgical strategies in France are mastectomy for pre-symptomatic. On the other hand, BCT is proposed to all patients after NAC according to clinical response, regardless their gBRCAm status. Moreover, in the case of BRCA mutation, local recurrence risk at 15 years is higher in the BCT group (23%) vs mastectomy (5%) (Pierce 2010). The aim of this retrospective one-institution analysis is to evaluate if the knowledge of gBRCAm status impact surgical decision.
Patients and methods
All patients who underwent BRCA genetic testing during NAC for ≥ 3cm breast cancer between 2012 and 2015 were included. BRCA testing was decided with each patient based on age, familial history of breast or ovarian cancer and histological characteristics of the tumor. Rapid germline BRCA mutation screening was performed through targeted next generation sequencing with a 25-genes panel including full coding sequence of BRCA1 & 2. Deleterious mutations were detected using MiSeq reporter and confirmed by Sanger sequencing before giving the results to the clinical geneticist, and finally used for the choice of surgical strategy. At the end of NAC (6 three-weeks cycles in our center), a shared-decision making for surgical procedure was performed, based on pre and post-NAC clinical and radiological features, and results of the genetic testing.
Results
A total of 25 patients (including three with bilateral cancer) were tested during NAC: mean age 38 years (26-64); mean clinical size 46 mm (20-130mm); histological types: triple negative (n=14), HER-2 positive (n=7), luminal (n=7). A germline BRCA mutation was detected in 10 patients (40%) : 8 BRCA1 and 2 BRCA2, including 8 patients among the 14 patients with a Manchester score &gt; 20 (6 BRCA1 & 2 BRCA2). Two patients were secondarily excluded (one being metastatic and one died during NAC), one of them having a gBRCAm status. All the 23 patients evaluable for the surgical procedure after NAC could be eligible for a BCT. All the 9 patients with gBRCAm status choose mastectomy in the shared-decision making procedure while a BCT was performed in 12 of the 14 remaining patients without BRCA mutation.
Discussion
In this highly selected subgroup of patients, gBRCAm rate is higher (40%) than the usual rate for BRCA testing (17% in our center). Regarding the rationale for BCT or mastectomy procedure in LABC or pre-symptomatic gBRCAm patients, the duration of NAC allows rapid germline BRCA screening that looks very useful considering the high incidence of mutation we observed and the impact on surgical final decision. Furthermore, in the group of high Manchester score (&gt;20), patients without BRCA mutation harbored incidental mutation, currently under analysis, especially on other genes involved in hereditary breast cancer, that could also be used as a compelling argument for mastectomy.
Citation Format: Tunon de Lara C, Bonnet F, Debled M, Lafon D, Breton-Callu C, Rarouk-Simonet E, Fournier M, Petit A, Bubien V, Quenel-Tueux N, Lagarde P, Longy M, Macgrogan G, Sevenet N. Rapid germline BRCA screening for locally advanced breast cancer changes surgical procedure after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-23.