Comparison of clinicopathological features in early-onset breast cancer patients with and without pathogenic genetic mutation.

Abstract

e13179 Background: Early-onset breast cancer (EOBC), particularly in women under 40, has been increasing. Approximately, 10% of women with breast cancer carry a pathogenic variant in a cancer-predisposing gene, including BRCA1 and BRCA2. However, the impact of these mutations on clinicopathological characteristics remains inconsistent, especially in resource-limited settings. This study aimed to compare the clinicopathological characteristics and outcomes of early-onset breast cancer patients with and without pathogenic genetic mutations including those associated with Hereditary Breast and Ovarian Cancer (HBOC) genes. Methods: This is a single-center retrospective study. The study included patients diagnosed with breast cancer between 1999 and 2024, aged 40 years or younger, who underwent hereditary genetic panel testing. Pathogenic mutations in genes associated with Hereditary Breast and Ovarian Cancer (HBOC) were classified as genetic mutations for the purposes of this study. Clinicopatological and germline genetic data were collected from patient surveys and medical records. Clinicopathological features and outcomes were compared between patients with and without mutations using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. Survival analyses were conducted using the Kaplan-Meier method. Results: A total of 144 patients were included in the study, with 53 patients having pathogenic HBOC mutations and 91 patients not having mutations. The median follow-up period was 56.1 months . Patients with pathogenic mutations were significantly younger at diagnosis (35 vs. 37 years; p = 0.02) compared to those without mutations. Among tumor subtypes, triple-negative breast cancer (TNBC) was significantly more frequent in patients with pathogenic mutations (42.2% vs. 17.3%, p = 0.02). Other characteristics, including BMI, smoking, alcohol consumption, histological type, family history of malignancy, median Ki-67 index, histological grade, recurrence status and stage at diagnosis, showed no significant differences. Among HER2-negative patients, the frequency of HER2-low was higher in the mutation-negative group (33.8% vs. 23.9%); however, the difference was not statistically significant. Recurrence rates and overall survival were similar between groups, with limited deaths hindering survival analysis. Conclusions: Outcomes were similar between patients with and without pathogenic mutations. Despite the small sample size and low event rates, our findings highlight the heterogeneity in early-onset breast cancer (EOBC). No significant differences in overall survival were observed. Further studies with larger patient cohorts are needed to investigate the numerically higher frequency of HER2-low in patients without pathogenic mutations compared to those with mutations.