ER-Positive Breast Cancer Distant Recurrence Risk Persists Long-Term After Endocrine Therapy

Metastatic breast cancer risk characterised for 15 years after women complete tamoxifen and/or aromatase inhibitor therapy

  • Date: 09 Nov 2017
  • Author: By Lynda Williams, Senior medwireNews Reporter
  • Topic: Breast Cancer

medwireNews: Women successfully treated for oestrogen receptor (ER)-positive breast cancer remain at risk for distant recurrence for at least 15 years after completing a 5-year course of endocrine therapy, say researchers who found initial tumour diameter and nodal status (TN) to be strongly associated with patient outcome.

The Early Breast Cancer Trialists’ Collaborative Group meta-analysis included 62,923 participants of 88 trials, all of whom were disease-free after completing 5 years of tamoxifen (63%) or aromatase inhibitor (17%) monotherapy or sequential treatment of these agents (20%) for early-stage, ER-positive breast cancer.

For patients with stage T1 disease, the cumulative risk of distant recurrence was 13% for those without any nodal involvement, rising to 20% for patients with one to three positive nodes and 34% with four to nine positive nodes. The corresponding risks for patients with stage T2 disease were 19%, 26% and 41%. 

Analysis of tumour grade data from 43,590 women and Ki-67 status from 7692 women revealed that these two factors “strongly” correlated with each other but individually were each only of “moderate” predictive value for distant recurrence. And assessment of progesterone receptor (n=54,115) or HER2 receptor status (n=15,418 nonusers of trastuzumab) suggested that neither significantly predicted the likelihood of metastases. 

In the 5–15 years after diagnosis, the risk of distant recurrence in women with T1 node-negative disease was 10% for those with low-grade disease, rising to 13% for moderate-grade disease and 17% for patients with high-grade disease. The likelihood of any recurrence or contralateral disease in these patients was 17%, 22% and 26%, respectively. 

Writing in The New England Journal of Medicine, the investigators say that the meta-analysis has “implications for long-term follow-up strategies and highlights the need for new approaches to reduce late recurrence.” 

Daniel Hayes, from the University of Michigan Comprehensive Cancer Center in Ann Arbor, USA, and co-authors suggest that extending endocrine therapy duration could be warranted to reduce the risk of distant recurrence, even in women with low-grade T1 node-negative disease.

“Recognition of the magnitude of the long-term risks of ER-positive disease can help women and their health care professionals decide whether to extend therapy beyond 5 years and whether to persist if adverse events occur”, they conclude.


Pan H, Gray R, Braybrooke J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 2017; 377: 1836–1846. DOI: 10.1056/NEJMoa1701830

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