Clinicopathological features of breast cancer in Ukrainian women with BRCA1 c.181T>G (p.Cys61Gly) variant: a case series

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Introduction BRCA1 c.181T>G (p.Cys61Gly) is a pathogenic founder genetic variant prevalent in Central and Eastern Europe. The data on its clinicopathological manifestations in Ukrainian patients remain limited. Aim This study aimed to characterize clinical presentation, tumor biology, and family history in Ukrainian women with BRCA1 c.181T>G variant. Materials and methods We conducted a single-centre case series of women with primary breast cancer (BC) and/or ovarian cancer (OC) harbouring BRCA1 c.181T>G genetic variant and treated at Lviv Regional Oncology Treatment and Diagnostic Center (Ukraine) between January 2024 and August 2025. Clinical presentation, tumor pathology, biomarker status, family history, treatment, and outcomes were analysed. Results Thirteen women aged 29–81 years (median 35 years) were included in this case series. Early-onset BC was recorded in 10 (76.9%) of patients diagnosed before 40 years. BC was the initial malignancy in 12 (92.3%) patients. OC occurred as a first tumor in 1 (7.7%) and as a subsequent cancer in 4 (30.8%) patients. Multiple malignancies were observed in 61.5% of patients, with intervals of 5–21 years between diagnoses. Family history revealed strong clustering of BC and OC across generations, often involving multiple affected relatives, consistent with hereditary breast and ovarian cancer syndrome phenotype. Among cases with known biomarker status (10/13), 2 were HER2-positive, 4 belonged to luminal-like type, and 4 cases represented triple negative BC. Most cases (10/13, 76.9%) were diagnosed at early tumor growth stage (pT1-2). However, more than half of primary tumors (8 of 13; 61.5%) had positive nodal status (pN1-2) reflecting invasive behaviour of cancer cells. Conclusions This Ukrainian case series demonstrates that the BRCA1 c.181T>G genetic variant is associated with early-onset breast cancer, variable tumor biology, frequent multiple primary cancers, and strong familial clustering. These observations support the need for expanded genetic testing, targeted surveillance, and corresponding risk reduction strategies tailored to Ukraine’s BRCA1 founder pathogenic variant landscape.