In a meta-analysis reported in The New England Journal of Medicine by Pan et al for the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), it was found that breast cancer recurs at a steady incidence following cessation of adjuvant endocrine therapy after 5 years, with the risk dependent on initial nodal involvement.
The meta-analysis included data from 88 trials involving 62,923 women with estrogen receptor–positive breast cancer who were disease-free after 5 years of adjuvant endocrine therapy. Kaplan-Meier and Cox regression analyses stratified according to trial and treatment were performed to examine associations of tumor diameter and nodal status (TN), tumor grade, and other factors with outcome during the period from 5 to 20 years.
Distant disease recurrence was found to occur steadily for the entire follow-up period, with an annual risk strongly associated with nodal status (P < .001); 20-year risks were 22% in women with no positive nodes, 31% in those with one to three positive nodes, and 52% in those with four to nine positive nodes. Among women with T1 disease, the risk of distant recurrence was 13% with no nodal involvement, 20% with one to three nodes involved, and 34% with four to nine nodes involved; among those with T2 disease, the risk was 19% with no nodal involvement, 26% with one to three involved nodes, and 41% with four to nine involved nodes. Similar associations were observed between TN status and risk of death from breast cancer, but no significant association was found between TN status and risk of contralateral breast cancer.
After adjustment for TN status, tumor grade and Ki67 status were of moderate independent predictive value for distant disease recurrence, whereas progesterone receptor status and HER2 receptor status were not predictive. During the 5 to 20 years of follow-up, the absolute risk of distant disease recurrence among patients with T1, N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease, with a corresponding risk of any recurrence or contralateral breast cancer being 17%, 22%, and 26%, respectively.
The investigators concluded: “After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant [disease] recurrence was strongly correlated with the original TN status, with risks ranging from 10% to 41%, depending on TN status and tumor grade.”
The study was funded by Cancer Research UK and others.
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