The impact of molecular subtype on breast cancer recurrence in young women treated with contemporary adjuvant therapy

Breast cancer is the leading cause of cancer death in women younger than 40 years. Triple-negative breast cancer (TNBC) and human epidermal growth factor receptor-2 (HER2) positive subtypes have a particularly poor prognosis in this age group. The purpose of this study was to compare rates of recurrence among breast cancer subtypes in young patients treated with modern adjuvant systemic therapy. A retrospective review of breast cancer patients managed at a major academic breast center between May 2000 and November 2014 was performed. We included 239 women with breast cancer who were diagnosed and treated at age ≤40 years. Clinical, pathological, therapeutic, and outcome data were recorded. Patients were classified into the following molecular subtypes: luminal A/B (estrogen receptor [ER] positive and/or progesterone receptor [PR] positive, and HER2 negative), luminal/HER2 (ER positive and/or PR positive, and HER2 positive), HER2- enriched (ER negative, PR negative, and HER2 positive) and TNBC (ER negative, PR negative, and HER2 negative). Descriptive statistics were used to characterize the study cohort. Kaplan-Meier survival analysis was performed to estimate recurrence-free survival (RFS). Median follow-up time was 29 months. Mean age was 34.5 years. Among all patients, 193 (80.8%) were diagnosed with Invasive breast cancer and 46 (19.2%) with ductal carcinoma in situ with or without microinvasion. Subclassification into molecular subtypes was complete for 199 patients among which, 50.7% were classified as luminal A/B, 21.1% luminal/HER2, 12.1% HER2-enriched and 16.1% TNBC. Of the 199 patients, 25.1% received neo-adjuvant chemotherapy and 59.2% received adjuvant chemotherapy. Among HER2-positive patients, 81.3% received HER2 directed therapy. Twenty-eight patients (11.7%) had recurrences (13 loco-regional, seven distant, and eight both). At 3 years, the HER2 subtype had the highest RFS 100%, compared to 91.1% in luminal A/B, 85.6% in luminal/HER2 and 81.9% in TNBC. In comparing outcomes among subtypes, the HER2 positive subtype was associated with improved RFS, likely reflecting the impact of HER2 directed therapy. Those young patients with triple-negative subtype continued to have the poorest outcomes.