Breast cancer (BC) may recur many years after primary diagnosis. We investigated the incidence of late breast cancer recurrence (BCR) (>= 10 years after primary surgery) and identified potential associations between clinico-pathological factors at baseline and late BCR.
Using the Danish Breast Cancer Group’s (DBCG) database we identified all women with incident stage I-III operable BC diagnosed during 1987-2002, who were alive and without a recurrence or new primary cancer 10 years after diagnosis. We derived an algorithm to identify late BCR using Danish population-based registries. Follow-up began 10 years after primary surgery date and continued until late BCR, death, emigration, second cancer or 31/12/2013. Crude incidence rates (IRs) per 1,000 person-years (PY) and cumulative incidence proportions (CIPs) for late BCR were calculated by patient- and tumor characteristics at baseline. Cox regression models were used to calculate hazard ratios (HRs), accounting for competing risks. The HRs were adjusted for tumor- and patient characteristics.
18,117 women of 31,528 (57%) reached year 10 without BC recurrence, a contralateral breast cancer or other primary cancer, and were followed for a total of 106,602 PY with a median follow-up of 4.9 years (IQR; 2.4-8.7). Of these 10-year survivors, 1,763 developed late BCR corresponding to an IR of 16.5 (95% CI, 15.8-17.3) per 1,000 PY and a CIP of 15% maximum 27 years after primary diagnosis. The CIP was higher among patients with estrogen receptor (ER)+ tumors, stage III disease and high nodal status. We found an adjusted HR of 3.0 (95% CI, 2.47-3.55) for patients with 4 or more positive lymph nodes versus patients with no lymph node involvement, an adjusted HR of 1.85 (95% CI, 1.59-2.15) for patients with stage III disease versus stage I disease and an adjusted HR of 0.57 (95% CI, 0.45-0.72) for patients with an ER- tumor versus patients with an ER+ tumor.
Our findings suggest that women with breast cancer can remain disease-free for at least ten years, but recurrences continue to occur from 10 to 27 years after primary diagnosis. Baseline tumor characteristics such as lymph node status, stage, and ER receptor status seems to be associated with late breast cancer recurrence.
Clinical trial identification
Legal entity responsible for the study
The Danish Cancer Society.
B. Ejlertsen: Research grant/Funding (institution), Research funding to my institution from NanoString, Roche, Novartis, and Oncology Venture: Rigshospitalet, Copenhagen University Hospital. All other authors have declared no conflicts of interest.