Four pathogenic variants co-occurring in a MINAS early-onset breast cancer

Abstract

Introduction Multilocus Inherited Neoplasia Allele Syndrome (MINAS) is a condition defined by the presence of germline pathogenic variants in more than one Cancer Susceptibility Gene (CSG). MINAS is still underreported in the literature and public databases. Since MINAS-related phenotypes are difficult to predict, case descriptions may contribute to risk assessment, treatment, and personalized surveillance for proband and relatives. Case Description: Here we report a unique case of early onset, bifocal, non-Triple Negative breast cancer in a 31-year-old woman. Fast metastatic dissemination involving the brain caused the death of the patient in a few months. Her multigene panel testing showed the co-occurrence of pathogenic variants in PALB2 (c.1221del; p.Thr408fs*40), ATM (c.8545C>T; p.Arg2849*), PMS2 (c.1919C>A; p.Ser640*), and MUTYH (c.1103G>A; p.Gly368Asp). The patient inherited the ATM and MUTYH variants from the mother, and PALB2 and PMS2 variants from the father. The brother inherited the maternal ATM and paternal PMS2 variants. A baseline imaging-based family screening excluded malignancies in both parents and in the brother. Tailored monitoring is ongoing based on the risk predicted by pathogenic variants identified in family members. Conclusions: Currently, there are no predictive tools available to determine organ-specific cancer risk in MINAS patients. Given the uncertainty in predicting the phenotypic effect of multiple variants in CSGs, ongoing clinical surveillance and sharing data from complex cases are crucial for improving risk stratification in this condition.