20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

Authors: Hongchao P, et. al.

Source: NEJM 2017;377:1836-46

www.nejm.org/doi/full/10.1056/NEJMoa1701830

Endocrine therapy (tamoxifen or an aromatase inhibitor) is routinely used for women who have had estrogen receptor (ER) positive breast cancer. The initial recommendations were for five years of use. This regimen reduces the rates of recurrence and improves breast cancer-specific survival. More recent information supports continuing therapy for 10 years because recurrence is reduced even further. However, some women have significant side effects from the medications and are unwilling to continue beyond five years.

The investigators recognized that, for a woman to decide to extend her endocrine therapy for 10 years, she must understand the risks and the benefits of doing so. The group investigated recurrence patterns among women with ER-positive, early stage breast cancer over an extended period of time.

Cases of over 62,000 women with ER-positive breast cancer were gathered. Tumors were 5 cm or less in size.  No more than 9 lymph nodes were involved per woman. Cases were followed to measure rates of recurrence and breast cancer-specific deaths. Follow up was 20 years.

Disease recurrence rates steadily rose for at least 15 years after the scheduled 5 years of planned endocrine therapy ended. Women with no positive nodes (N0) had a 20 year recurrence rate of 22%. The rate was 31% for women with 1-3 positive nodes (N1-3). The rate rose to 52% for women with 4-9 positive nodes (N4-9). Calculations found that the risk of death at 20 years was 15% with N0 disease, 28% with N1-3 disease and 49% with N4-9 disease.

As with nodal status, tumor sizes were directly related to rates of recurrence and breast cancer-specific death. These rates also steadily rose over the observed time period of 20 years. Even women with smaller, node-negative disease had recurrence risks of 13% up to year 20. Tumor grade was also related to outcomes, but did not seem as significant as lymph node status and tumor size over time.

The investigators tried to identify a group of women for whom only 5 years of endocrine therapy would be sufficient. They determined that only women over 70 or in poor health should be considered for such a short regimen, because their risk of death from other causes may be higher than the risk of death from breast cancer.

There were some drawbacks to the study design, including the fact that some of the participants did not complete 5 years of endocrine therapy. This may have made the outcomes appear worse than they actually were. Nonetheless, the information remains overwhelming that women with early stage, ER-positive breast cancer are expected to benefit from continuing endocrine therapy for 10 years.