RESUMEN
Even though male breast cancer (MBC) risk encompasses both genetic and environmental aetiologies, the primary risk factor is a germline pathogenic variant (PV) or likely pathogenic variant (LPV) in BRCA2, BRCA1 and/or PALB2 genes. To identify new potential MBC-specific predisposition genes, we sequenced a panel of 585 carcinogenesis genes in an MBC cohort without BRCA1/BRCA2/PALB2 PV/LPV. We identified 14 genes carrying rare PVs/LPVs in the MBC population versus noncancer non-Finnish European men, predominantly coding for DNA repair and maintenance of genomic stability proteins. We identified for the first time PVs/LPVs in PRCC (pre-mRNA processing), HOXA9 (transcription regulation), RECQL4 and WRN (maintenance of genomic stability) as well as in genes involved in other cellular processes. To study the specificity of this MBC PV/LPV profile, we examined whether variants in the same genes could be detected in a female breast cancer (FBC) cohort without BRCA1/BRCA2/PALB2 PV/LPV. Only 5/109 women (4.6%) carried a PV/LPV versus 18/85 men (21.2%) on these genes. FBC did not carry any PV/LPV on 11 of these genes. Although 5.9% of the MBC cohort carried PVs/LPVs in PALLD and ERCC2, neither of these genes were altered in our FBC cohort. Our data suggest that in addition to BRCA1/BRCA2/PALB2, other genes involved in DNA repair/maintenance or genomic stability as well as cell adhesion may form a specific MBC PV/LPV signature.
RESUMEN
INTRODUCTION: More and more French cancer patients are offered by their physicians having their genetic characteristics analyzed (diagnosis, adaptation of treatment plans, etc.). In oncology, considering the development of personalized medicine, these analyses are commonplace. Analyses of germline (hereditary) genetic characteristics require information from patients who must sign an informed consent (article 16.10 of the Civil Code and articles L. 1131-3 and L. 1122-1-1 of the Public Health Code). However, prescribing physicians are rarely geneticists and have little training in genetics. Patients report that few are able to answer their questions and often sign a consent that is not truly informed. METHODS: To identify the genetic knowledge and training needs of prescribers, we conducted an online survey of physicians prescribing genetic testing in oncology between January and March 2020. The survey consisted of 17 closed questions and 3 open questions. RESULTS: We obtained 35 usable questionnaires which show that 50% of the prescribing physicians questioned lack knowledge of genetics, but do not express a need for training. They were interested in the provision of a digital teaching aid for patients. DISCUSSION: We have therefore made a film for patients, available in free access, which aims to shed light on the analysis of genetic characteristics. The film helps physicians to explain the offered analyses and their consequences (https://youtu.be/5lWUSsteavs).
RESUMEN
One of the main challenges in cancer genetics is responding to the exponential demand for genetic counseling, especially in patients with breast and/or ovarian cancer. To address this demand, we have set up a new procedure, based on pre-genetic counseling telephone interviews (PTI) followed by routing of patients: D1, a PTI is scheduled within 14 days; D7-D14, genetic counselors perform a 20 min PTI in order to establish a pre-genetic counseling file, by collecting personal and family medical history via a structured questionnaire and; D10-17, routing: pre-genetic counseling appointment files are analyzed by a cancer geneticist with 3 possible conclusions: (a) priority face-to-face genetic counseling (FTFGC) appointment with a cancer geneticist, if the genetic test results have an immediate therapeutic impact; (b) non-priority FTFGC with a genetic counselor, or (c) no FTFGC required or substitution by a more appropriate index case. In the context of breast and/or ovarian cancer, 1012 patients received PTIs, 39.1% of which did not lead to FTFGC. The mean delay for non-priority FTFGC was maintained at 18 weeks and priority FTFGC appointments were guaranteed within 8 weeks. The required resources for 1012 patients was estimated at 0.12 FTE secretaries, 0.62 FTE genetic counselors and 0.08 FTE cancer geneticists and the procedure was shown to be cost-effective. This new procedure allows the suppression of up to 1/3 of appointments, guarantees priority for appointments with therapeutic impact and optimizes the interaction and breakdown of tasks between genetic counselors and cancer geneticists.
