Patterns of Recurrence in Node-Negative Breast Cancer

The recurrence pattern for patients with early-stage breast cancer can be highly variable, and there is an evolving appreciation that biology can trump, or at least complement, clinical characteristics of a tumor with respect to recurrence risk, even in patients with axillary node-negative (ANN) disease.

To determine patterns of recurrence and survival in ANN breast cancer according to disease subtype, the International Breast Cancer Study Group (IBCSG) analyzed 1951 early-stage ANN patients enrolled in two IBCSG studies: IBCSG VIII randomized 1063 patients to 6 cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by 18 months of goserelin, 6 cycles of CMF alone, or 24 months of goserelin alone; IBCSG IX randomized 1669 postmenopausal patients to 3 cycles of CMF followed by tamoxifen for 57 months or tamoxifen alone for 5 years. Tumors were classified by immunohistochemical analysis into four subtypes: triple negative (TN), HER2-positive, luminal A (LA), or luminal B (LB). Breast cancer-free interval (BCFI) was defined as the duration from randomization to invasive breast cancer recurrence.

At median follow-up of 12.5 years, the 10-year BCFI rate was higher for LA (86%) versus LB (76%), HER2 (73%), or TN (71%) cohorts. TN and HER2 cohorts had a higher risk for BCFI events in the first 4 years after diagnosis (pre-trastuzumab era), and LB cohorts had continuously higher risk for BCFI events over time versus LA cohorts. Ten-year overall survival was higher for LA (89%) versus LB (83%), HER2 (77%), or TN (75%) cohorts. Bone as site of first recurrence was more common for LB versus other subtypes. Visceral recurrence as first site was less common for the LA subtype; similar incidence was observed among the other subtypes when chemotherapy was administered.