Impact of peridiagnostic genetic counseling and germline testing on treatment decisions for patients with triple negative breast cancer undergoing pembrolizumab-chemotherapy neoadjuvant approach.
Authors: Bruno Luisina Ines , Alberto Guillermo , Lapuchesky Laura Sabina , Rodriguez Andres , Waisberg Federico , Enrico Diego Hernán , Ostinelli Cristian Alexis , Paletta Claudio Alfredo , Petracci Fernando Enrique , Amat Mora , Pombo Maria Teresa , Rivero Sergio , Coló Federico Andrés , Loza Carlos Martin , Fabiano Verónica Yamila , Chacon Reinaldo D. , Chacon Matias Rodrigo , Nadal Jorge Carlos , Nervo Adrian , Costanzo Maria Victoria 
Published: June 2024

e12633

Background: Triple negative breast cancer (TNBC) has been globally associated with a high risk of carrying pathogenic or likely pathogenic (P/LP) variants in germline breast cancer (BC) susceptibility genes (BCSG). Immunotherapy- based Neoadjuvant (pembro-NA) treatment is the preferred approach for localized, T2 or node positive TNBC. To the best of our knowledge, information about peridiagnostic genetic counseling (PGC), germline status and their impact on patients (pts) undergoing this treatment approach has not been reported yet. Our aim was to describe the feasibility and impact of PGC in TNBC pts treated with pembro-NA and to compare clinical benefits between carriers and wild type (WT) pts in a real- world (RW) setting. Methods: Consecutive, localized TNBC pts who received pembro-NA were enrolled, between March 2022 and August 2023 in a private Argentinian institution. Informed consent was obtained, and medical information collected from medical records and an institutional GC registry. Clinical benefit in terms of pathological complete response (pCR) was analyzed according to BCSG status. Univariate analyses, including chi-square, Fisher and Wilcoxon tests were performed when appropriate. p<0.05 was considered for statistical significance. Results: 47 pts were ascertained. 36.5% (15/41) tested positive for BCSG: 93% (14/15) for BRCA1-2 genes (gBRCA+). No differences were observed in pts ages, with medians of 45 years [IQR 40-50.5] vs 40 [IQR 35-48] among non-carriers versus carriers, respectively (p=0.56). Also, stage at presentation was similar for both subgroups (II: 77.8% vs 60%, III: 14.8% vs 33.3; p=0.37). PGC outcomes: 1/47 (2%) was previously diagnosed as BRCA1 positive (gBRCA+), 1/47 (2%) died before PGC assessment; 85% (40/47) were assessed locally; 64% (30/47) revealed a positive cancer family history; 93% (38/41) were tested through multi-gene panel testing. Median time from diagnosis to first GC appointment was 11.4 weeks (wk) and to disclosure of genetic results by a geneticist or oncologist was 13 wk. Treatment outcomes: 81% (38/47) had completed pembro-NA; one (2%) progressed in the WT group. pCR was achieved in 78.9% (30/38), with no differences between groups (p=0.46). Olaparib or capecitabine were added in pts that did not achieve pCR according to gBRCA status. Notably, 73% carriers versus 37.5% WT pts underwent risk-reducing bilateral mastectomy (p=0.0304). Conclusions: PGC is feasible in a RW scenario of limited resources such as in Argentina. We found a high rate of carriers, mostly gBRCA+, in which surgical decisions and post-NA treatments were determined considering germline status findings. Although efficacy differences between gBRCA+ and WT were not found, further research and data on long-terms outcomes are needed to assess comparative results.