Multilocus Inherited Neoplasia Alleles Syndrome in a Patient With BRCA2-Associated Breast Cancer and MLH1-Related Lynch Syndrome.

Abstract

Multilocus inherited neoplasia alleles syndrome (MINAS) is a rare but increasingly recognized entity characterized by germline pathogenic variants in multiple cancer susceptibility genes, leading to overlapping hereditary cancer syndromes. The growing use of next-generation sequencing (NGS) and comprehensive genetic testing has increased MINAS detection, with an estimated 1.37% prevalence among hereditary cancer patients. Genes commonly implicated include BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, APC, TP53, PTEN, and STK11, conferring a higher risk of multiple primary malignancies. We describe a case of a postmenopausal woman initially diagnosed with Stage IIIB luminal A breast carcinoma, who developed contralateral breast recurrence with supraclavicular and pulmonary metastases, responding completely to ribociclib and letrozole. Given her early-onset breast cancer, genetic testing of her hereditary cancer risk revealed BRCA2 and MLH1 germline variants, confirming MINAS syndrome. Subsequent evaluation identified colonic adenocarcinoma (Stage IIIB, MLH1/PMS2 deficiency), leading to total colectomy, hysterectomy, and bilateral salpingo-oophorectomy. Surveillance was proposed for colon cancer, while ribociclib and letrozole were continued for breast cancer. This case highlights the clinical complexity of MINAS syndrome. The comprehensive genomic profiling is critical for guiding targeted therapy, immunotherapy, and surgical decision-making, optimizing outcomes in this high-risk population.