Even after 5 years of adjuvant endocrine therapy, women with early-stage estrogen receptor (ER)-positive breast cancer experienced a steady rate of recurrences for as long as 20 years, according to the results of a meta-analysis published in the New England Journal of Medicine. Even women with low-grade T1N0 disease had an absolute risk for recurrence of 10% during years 5 to 20 of study follow-up.
“This finding has implications for long-term follow-up strategies and highlights the need for new approaches to reduce late recurrence,” wrote Hongchao Pan, PhD, of the Nuffield Department of Population Health at the University of Oxford in the United Kingdom, and colleagues. “Recognition of the magnitude of the long-term risks of ER-positive disease can help women and their healthcare professionals decide whether to extend therapy beyond 5 years and whether to persist if adverse events occur.”
According to the study, endocrine therapy given for up to 5 years significantly reduces risk for recurrence during and after treatment in women with early-stage ER-positive breast cancer. Extending endocrine therapy beyond 5 years is possible but associated with additional side effects. Pan and colleagues conducted this meta-analysis to determine the absolute risk for distant recurrence if patients were to stop therapy at 5 years.
The study looked at results from 88 trials that involved more than 62,000 women with ER-positive breast cancer who were disease free after 5 years of scheduled endocrine therapy.
The researchers found a correlation between risk for distant recurrence and original TN status. Patients with T1 disease had a risk for distant recurrence of 13% with no nodal involvement (T1N0). This risk increased to 20% with one to three nodes involved (T1N1-3), and further to 34% with four to nine nodes involved (T1N4-9). The risk increased further for patients with T2 disease—to 19% with T2N0, 26% with T2N1-3, and 41% with T2N4-9.
A similar association was also found for the risk for death from breast cancer, which was also dependent on TN status. However, risk for contralateral breast cancer was not.
From year 5 to 20 of the study period, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease. Corresponding risks for any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively.
The researchers noted that they could not assess the relevance of use of chemotherapy to prognosis after year 5, “since the women who received chemotherapy and those who did not receive chemotherapy differed in the extent of nodal involvement, tumor size, tumor grade, and perhaps unrecorded selection factors.”
“These findings underline the need to help women who are receiving endocrine therapy to discover whether any symptoms are actually caused or exacerbated by therapy,” the researchers wrote. “Such patients could try stopping treatment for short periods or switching from one agent to another.”