CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype

• DOI: 10.1001/jamanetworkopen.2024.7862
• Publication Date: 2024-04-23T15:01:26Z
• Authors: Giovanni Corso; Elena Marino; Cristina Zanzottera; Carla Oliveira; Loris Bernard; Debora Macis; Joana Figueiredo; Joana Pereira; Patrícia Carneiro; Giulia Massari; Massimo Barberis; Alessandra Marghe...; Sergio Vincenzo T...; Elham Sajjadi; Claudia Sangalli; Sara Gandini; Oriana D’Ecclesiis; Cristina Maria Tr...; Anna Rotili; Filippo Pesapane; Luca Nicosia; Carlo La Vecchia; Viviana Galimberti; Elena Guerini-Rocco; Bernardo Bonanni; Paolo Veronesi
• Keywords: CDH1

Importance Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast (LBC) in the so-called hereditary (HDGC) syndrome. However, some circumstances, LBC can be first manifestation of this syndrome absence manifestation. Objectives To evaluate frequency women (HLBC) phenotype, somatic gene inactivation variant carriers’ tumor samples, association genetic profiles clinical-pathological data survival. Design, Setting, Participants This single-center, longitudinal, prospective cohort study was conducted from January 1, 1997, to December 31, 2021, follow-up until 2023. Women seen at European Institute Oncology were included. Testing , BRCA1 BRCA2 genes performed. Somatic profiling assessed carriers. Main Outcomes Measures Accurate estimates prevalence among patients HLBC sequence alteration The Kaplan-Meier method a multivariable Cox proportional hazards regression model applied overall disease-free survival analysis. Results Of 5429 cases primary LBC, familial phenotype accounted 1867 (34.4%). A total 394 tested, whom 15 unrelated families identified. Among these variants, 6 (40.0%) P/LP, an 1.5% (6 394). probands P/LP 5 (83.3%) had positive family history BC only 1 (16.7%) sporadic juvenile early-onset LBC. No identified An inactivating mechanism (second hit) 4 explored matched samples (66.7%) carriers significantly lower age diagnosis compared group carrying unknown significance benign (42.5 [IQR, 38.3-43.0] vs 51.0 45.0-53.0] years; P = .03). Conclusions Relevance In study, individuals not fulfilling classic clinical criteria HDGC screening, suggesting that identification may provide novel test early and/or BC.