Evaluating genetic features and clinical characteristics of young women diagnosed with breast cancer by the age of 35.

Abstract

10580 Background: Breast cancer in young women tends to be more aggressive with a unique distribution of molecular phenotypes compared to the general population. We evaluated the clinical characteristics and germline genetic test results in this cohort. Methods: We performed a single center retrospective review of 167 women diagnosed with breast cancer by 35, treated at our institution between the years 2013 to 2023. We reviewed medical records under Institutional Review Board approval for demographics, family history, tumor characteristics, surgical interventions performed, germline genetic test results, and number of pathogenic mutations identified. We used both descriptive and comparative quantitative statistics (student’s t test, Mann Whitney U Test and Chi Square tests) to compare data between patients with a pathogenic mutation and those without a pathogenic mutation. Results: Germline genetic testing was performed in 92.2% of individuals. The majority (81.4%) had no pathogenic mutation, whereas 15.6% had a pathogenic mutation implicated in hereditary breast cancer, and 3.0% had a pathogenic mutation not implicated in hereditary breast cancer. Our population was diverse - 60.4% white, 25.1% black, 7.8% Hispanic, and 6.5% Asian. Most patients had tumors that were high grade (56.3%), had a bilateral mastectomy performed (57.4%), did not have recurrence (87.4%), had exposure to oral contraceptives prior to diagnosis (59.9%), and had a family history of breast cancer (52.1%). 3.5% of patients were pregnant at the time of diagnosis. 26 patients were found to have pathogenic mutations implicated in hereditary breast cancer including BRCA1 (10), BRCA2 (10), CHEK2 (2), TP53 (2) and 88.5% of these patients underwent bilateral mastectomy. A higher proportion of patients with a pathogenic mutation were found to be progesterone receptor (PR) negative (56.8% vs 34.9; p = 0.029), undergo bilateral mastectomy (80.8% vs 53.2%; p = 0.009), be stage 1 at diagnosis (50.0% vs 19.1%; p < 0.001), have invasive ductal carcinoma (80.8% vs 59.6%; p = 0.040), and have a family history of breast cancer (73.1% vs 48.9%; p = 0.024) compared to those with no pathogenic mutation. While not statistically significant, a higher proportion of patients with pathogenic mutations experienced recurrence (19.2% vs 11.3%; p = 0.330). Conclusions: Our study showed that breast cancer diagnosed in young women has a more aggressive disease biology with 56.3% of the cohort found to have grade 3 disease. A higher proportion of those who had a pathogenic mutation implicated in hereditary breast cancer were found to be PR negative, underwent bilateral mastectomy, and had a family history of breast cancer. As our study was an exploratory observational study, further prospective multi-center studies are needed to help corroborate our findings and to better elucidate the potential clinical significance.