Changes in Temporal Patterns and Risk of Recurrence in Breast Cancer Between 1986–1992 and 2004–2008
In a Canadian study reported in Journal of Clinical Oncology, Cossetti and colleagues found that temporal patterns of breast cancer relapse according to estrogen receptor and HER2 status in the period 2004–2008 were similar to those in 1986–1992 but at markedly reduced relapse rates. Improvement in outcomes between the two periods was greatest in HER2-positive and estrogen receptor–negative/HER2-negative subgroups.
Study Details
The study involved data from 7,178 patients referred to the British Columbia Cancer Agency with biopsy-proven stage I to III breast cancer diagnosed between 1986 and 1992 (early cohort, n = 3,589) and between mid-2004 and 2008 (late cohort, n = 3,589), with late-cohort patients matched to early-cohort patients for stage, grade, and estrogen receptor and HER2 status. The primary endpoint was hazard rate of relapse (HRR) according to biomarker status. Overall, 70.8% of patients had estrogen receptor–positive/HER2-negative disease, 6.9% had estrogen receptor–positive/HER2-positive disease, 6.6% had estrogen receptor–negative/HER2-positive, and 15.8% had estrogen receptor–negative/HER2-negative disease.
Similar Patterns, Reduced Risk According to Estrogen Receptor Status
In the overall population, the HRR was approximately halved in all yearly intervals to year 9 in the late vs early cohort.
The HRR for estrogen receptor–negative tumors was higher than the HRR for estrogen receptor–positive tumors during the initial years of follow-up in both cohorts. In the early cohort, the HRR for estrogen receptor–negative tumors was higher in the first 4 years, with the HRR for estrogen receptor–positive tumors exhibiting a smooth peak in the first 3 years and remaining relatively stable after year 5. The HRRs for estrogen receptor–negative and estrogen receptor–positive tumors crossed between years 4 and 5.
In the late cohort, the HRR for estrogen receptor–negative tumors was also higher in the initial 4 years, with the HRR for estrogen receptor–positive patients having a slight peak in the first 3 years and remaining relatively stable after year 5 and the HRRs for estrogen receptor–negative and estrogen receptor–positive patients also crossing between years 4 and 5.
The HRR ratios for the late vs early cohort were 0.52, 0.39, 0.56, 0.52, 0.51, 0.41, 0.52, 0.26, and 0.35 by year of follow-up among estrogen receptor–positive patients and 0.54, 0.50, 0.50, 0.55, 0.41, 0.50, 0.50, 0.43, and 0 by year of follow-up among estrogen receptor–negative patients.
By Estrogen Receptor and HER2 Status
For estrogen receptor–positive/HER2-negative tumors, the HRR ratio for the late vs early cohort ranged from 0.30 to 0.62 by year of follow-up. For estrogen receptor–positive/HER2-positive patients, a peak of recurrence in the first 5 years in the early cohort was not observed in the late cohort; HRR ratios ranged from 0 to 0.55.
For estrogen receptor–negative/HER2-positive disease, a peak of relapse in the early cohort was also present in the late cohort but at reduced magnitude; HRR ratios were < 0.50 during the initial 5 years of follow-up, with few recurrences observed thereafter. For estrogen receptor–negative/HER2-negative disease, a peak of recurrence during the first 5 years in the early cohort was also present in the late cohort; HRRs were reduced in the late cohort but to a lesser degree than in other subgroups (HRR ratios = 0.55 to 0.87 during first 7 years of follow-up and 0 thereafter). HRRs were lower in the late cohort for all disease stages and grades.
Mortality
The hazard rate of death (HRD) was decreased in the late vs early cohort but to a lesser degree than HRR. The greatest relative HRD reductions for the late vs early cohorts were observed in HER2-positive disease, whereas reductions were not observed in all years of follow-up among patients with HER2-negaitve disease. In particular, HRDs were lower in the late cohort for all subgroups during follow-up except for the first year among estrogen receptor–positive/HER2-negative patients (HRD ratio 2.60) and estrogen receptor–negative/HER2-negative patients (HRD ratio 1.19), the 6th year for estrogen receptor–positive/HER2-negative patients, and the 9th year for estrogen receptor–negative/HER2-negative patients. The HRD was higher for estrogen receptor–negative patients in the first years after diagnosis in both cohorts. Among estrogen receptor–positive patients, the HRD increased over the years and crossed the HRD for estrogen receptor–negative patients at year 6 in the early cohort and year 5 in the late cohort.
The investigators concluded: “Although the pattern of relapse remains similar, there has been a significant improvement in [breast cancer] relapse-free survival. Outcomes have improved for all [breast cancer] subtypes, especially HER2-positive and estrogen receptor–negative/HER2-negative [breast cancer], with the early spike in disease recurrence markedly decreased. These contemporary hazard rates are important for treatment decisions, patient discussions, and planning clinical trials of early [breast cancer].”
Karen A. Gelmon, MD, of the British Columbia Cancer Agency, is the corresponding author for the Journal of Clinical Oncology article.
The authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
