A new study has reported that only the triple negative breast cancer subtype is associated with increased risk of locoregional recurrence in early stage breast cancer patients treated with lumpectomy and modern systemic therapy. Triple negative refers to breast cancer that is estrogen receptor negative (ER-), progesterone receptor negative (PR-), and does not overexpress human epidermal growth factor receptor 2 (HER2). Locoregional recurrence is recurrence in the breast, chest wall, or lymph nodes. Both triple negative and HER2+ disease have been associated with increased risk of locoregional recurrence in earlier studies of breast-conserving surgery (typically, lumpectomy).
In these studies, fewer patients received systemic therapy, including HER2-targeted therapy (Herceptin), compared with recent standards. The present study included 415 patients with invasive breast cancer who received breast-conserving surgery between 1992 and 2009. The patients had a median age of 54 and were followed for a median of 60 months. Forty eight percent of the patients received chemotherapy (anthracycline/taxane 34%, Herceptin-containing 4%, other 10%). Endocrine therapy (aromatase inhibitor, tamoxifen) was given to 67%.
Receptor status was available in 301 patients and were used to approximate subtypes: 66% luminal A, 9% luminal B, and 5% HER2+, and 20% basal (triple negative). These are molecular phenotypes, a new way to categorize breast cancer subtypes as determined by gene expression profiling. Luminal A tumors are strongly estrogen receptor positive (ER+) and progesterone receptor positive (PR+) and not HER2 overexpressing, with low tumor grade and low proliferation. Luminal B are weak to moderate ER+/PR+ and can be HER2- or HER2+. Luminal B tumors may have low tumor grade, but have higher proliferation and DNA instability than luminal A tumors. Basal tumors are most often triple negative.
There were a total of 11 locoregional recurrences, 15 distant metastases, and 20 deaths during the study period. The estimated 10-year progression-free survival rate was 85.4% and the overall survival rate was 90.5%. The five-year cumulative incidence of locoregional recurrence was 2.8%; the 10-year incidence was 4.5%. On single variable analysis, triple negative compared to luminal A and tumor size over 2 cm compared to up to 2 cm were significant prognostic factors for locoregional recurrence as first relapse. On multivariate analysis, only triple negative subtype retained statistical significance; other subtypes, including luminal B/HER2+ combined subtypes, were not significant. The authors conclude that long-term clinical outcomes were excellent in this cohort of breast cancer patients treated with breast-conserving surgery and modern systemic therapy, with 10-year locoregional recurrence of 4.5% and overall survival of 90.5%. Triple negative subtype was an independent predictor for locoregional recurrence. On the other hand, HER2+ subtype was not associated with increase in locoregional recurrence in this cohort treated with breast-conserving surgery and Herceptin.