A comprehensive study on surveillance outcomes of a male population followed at a hereditary breast cancer high-risk consultation at a Portuguese tertiary hospital.

Introduction: Men born with pathogenic/likely pathogenic variants in genes associated with the Hereditary Breast and Ovarian Cancer Syndrome have a higher risk to develop breast cancer and other cancers (such as prostate cancer) and should undergo adequate surveillance protocols in highly specialized Centers.

Methods: A retrospective study was conducted to assess these genetic variants' epidemiological and phenotypical manifestations in male carriers, as well as the efficacy of the surveillance protocol and compliance toward it through a survey. During follow-up, a genetic panel for testing was implemented, the starting age for surveillance was delayed, and the six-month screening interval was extended to annual.

Differences among a Portuguese cohort of BRCA pathogenic/likely pathogenic variants carriers choosing risk-reducing mastectomy or intensive breast surveillance.

Purpose: Women with BRCA1 and BRCA2 (BRCA1/2) pathogenic/likely pathogenic (P/LP) variants have a higher risk to develop breast and ovarian cancer. In structured high-risk clinics, risk-reducing measures are adopted. This study aimed at characterizing these women and identify factors that may have influenced their choice between risk reduction mastectomy (RRM) and intensive breast surveillance (IBS).

Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the European Reference Network on Genetic Tumour Risk Syndromes.

Background: Truncating pathogenic or likely pathogenic variants of CDH1 cause hereditary diffuse gastric cancer (HDGC), a tumour risk syndrome that predisposes carrier individuals to diffuse gastric and lobular breast cancer. Rare CDH1 missense variants are often classified as variants of unknown significance. We conducted a genotype-phenotype analysis in families carrying rare CDH1 variants, comparing cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV; analysed jointly) or missense variants of unknown significance, assessing the frequency of families with lobular breast cancer among PV/LPV carrier families, and testing the performance of lobular breast cancer-expanded criteria for CDH1 testing.

The c.1901C>T Variant: A Founder Variant in the Portuguese Population with Severe Impact in mRNA Splicing.

Hereditary diffuse gastric cancer (HDGC) caused by variants predisposes to early-onset diffuse gastric (DGC) and lobular breast cancer (LBC). In Northern Portugal, the unusually high number of HDGC cases in unrelated families carrying the c.1901C>T variant (formerly known as p.

Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease.

Background And Aims: The time course for the development of clinically significant hereditary diffuse gastric cancer (HDGC) is unpredictable. Little is known about the progression from preclinical, indolent lesions to widely invasive, aggressive phenotypes. Gastroendoscopy often fails to detect early lesions, and risk-reducing/prophylactic total gastrectomy (PTG) is the only curative approach.