Breast Cancer Diagnosed in Young Women ≤ Age 35: Effects of Germline Pathogenic Variants, Cancer Subtypes, Tumor-Related Characteristics, and Pregnancy-Associated Diagnosis on Outcomes

Abstract Background While breast cancer (BC) is uncommon in women ≤ age 35, women in this age group may have more aggressive cancer subtypes and high-risk pathogenic variants (HRPV). Higher recurrence and mortality rates in young patients may be related to differences in tumor biology, pathologic mutation status, or treatment. The purpose of this study was to evaluate germline mutation status, and other factors that affect recurrence-free survival (RFS) and overall survival (OS) in young women with BC. Materials/Methods This was a retrospective study of women diagnosed with BC at age ≤ 35 at Allina Health System from 2000 – 2017 (n= 306). Information was collected on germline mutation status, tumor characteristics (grade, hormone receptor and human epidermal growth factor receptor 2 [HER2]), molecular subtype, pregnancy-associated cancers, and treatment. Survival analyses using Kaplan Meier curves were conducted for RFS and OS. Results With mean follow-up of 6.5 years, OS was 87.0% for invasive cancers, RFS was 84.7%; 69% obtained genetic testing, and 26.9% had (HRPV). There were no differences in RFS or OS between patients with HRPV versus unknown/low/moderate risk variants. Recurrence analysis showed increased recurrence rates in Luminal B-like cancers followed by triple negative and HER2 positive cancers (p = 0.041). Pregnancy-associated BC diagnoses, angiolymphatic invasion and tumor stage were associated with reduced OS. In spite of young age at diagnosis, nearly a third of patients did not receive germline genetic testing. Conclusions Similar survival patterns were found between women with HRPV versus no known mutations. Luminal B-like subtype, pregnancy-associated BC, angiolymphatic invasion and cancer stage were associated with reduced OS.