Genetic Testing of Breast Cancer Patients with Very Early-Onset Breast Cancer (≤30 Years) Yields a High Rate of Germline Pathogenic Variants, Mainly in the BRCA1, TP53, and BRCA2 Genes.

Early-onset breast cancer constitutes a major criterion for genetic testing referral. Nevertheless, studies focusing on breast cancer patients (≤30 years) are limited. We investigated the contribution and spectrum of known breast-cancer-associated genes in 267 Greek women with breast cancer ≤30 years while monitoring their clinicopathological characteristics and outcomes. In this cohort, a significant proportion (39.7%) carried germline pathogenic variants (PVs) distributed in 8 genes. The majority, namely 36.7%, involved , and . PVs in were the most prevalent (28.1%), followed by (4.5%) and BRCA2 (4.1%) PVs. The contribution of PVs in , , , , and was limited to 3%. In the patient group ≤26 years, PVs were significantly higher compared to the group 26-30 years ( = 0.0023). A total of 74.8% of carriers did not report a family history of cancer. Carriers of PVs receiving neoadjuvant chemotherapy showed an improved event-free survival ( < 0.0001) compared to non-carriers. Overall, many women with early-onset breast cancer carry clinically actionable variants, mainly in the and genes. The inclusion of timely testing of in these patients provides essential information for appropriate clinical management. This is important for countries where reimbursement involves the cost of genetic analysis of only.