Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V

Abstract

Purpose: Predicting the pattern of recurrence can aid in the development of targeted surveillance and treatment strategies. We identified patient populations that remain at risk for an event at a median follow-up of 24 years from the diagnosis of operable breast cancer.

Patients and methods: International Breast Cancer Study Group clinical trials I to V randomly assigned 4,105 patients between 1978 and 1985. Annualized hazards were estimated for breast cancer-free interval (primary end point), disease-free survival, and overall survival.

Results: For the entire group, the annualized hazard of recurrence was highest during the first 5 years (10.4%), with a peak between years 1 and 2 (15.2%). During the first 5 years, patients with estrogen receptor (ER)--positive disease had a lower annualized hazard compared with those with ER-negative disease (9.9% v 11.5%; P = .01). However, beyond 5 years, patients with ER-positive disease had higher hazards (5 to 10 years: 5.4% v 3.3%; 10 to 15 years: 2.9% v 1.3%; 15 to 20 years: 2.8% v 1.2%; and 20 to 25 years: 1.3% v 1.4%; P < .001). Among patients with ER-positive disease, annualized hazards of recurrence remained elevated and fairly stable beyond 10 years, even for those with no axillary involvement (2.0%, 2.1%, and 1.1% for years 10 to 15, 15 to 20, and 20 to 25, respectively) and for those with one to three positive nodes (3.0%, 3.5%, and 1.5%, respectively).

Conclusion: Patients with ER-positive breast cancer maintain a significant recurrence rate during extended follow up. Strategies for follow up and treatments to prevent recurrences may be most efficiently applied and studied in patients with ER-positive disease followed for a long period of time.

Fig 1.

CONSORT diagram showing the analytic population according to estrogen receptor (ER) status for the five clinical trials.

Fig 2.

Annual hazard of breast cancer recurrence (A) for 4,105 patients included in International Breast Cancer Study Group trials I to V overall, (B) according to known estrogen receptor (ER) status (n = 2,956), (C) according to number of positive nodes for patients with ER-positive disease (n = 1,808), and (D) according to number of positive nodes for patients with ER-negative disease (n = 1,148). Vertical lines indicate 95% CI of the hazard.

Fig 3.

Kaplan-Meier curves according to known estrogen receptor (ER) status for the end points of (A) breast cancer–free interval (BCFI), (B) disease-free survival (DFS), and (C) overall survival (OS). Two-sided P values based on tests for interaction of ER status and survival times are each P < .001, indicating significant nonproportionality of hazards over time.