20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years
The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment.
In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients’ outcomes during the period from 5 to 20 years.
Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, 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; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively.
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 recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.)
Supported by core funding from Cancer Research UK, the British Heart Foundation, and the Medical Research Council (MRC) to the Clinical Trial Service Unit and MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford. Drs. Taylor and McGale are supported by a grant (C8225/A21133) from Cancer Research UK.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the women who entered these trials and their caregivers, the practitioners who conducted the studies and shared their data through the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), and the past and present members of the EBCTCG secretariat.
From the Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford (H.P., R.G., J. Braybrooke, C.D., C.T., P.M., R.P.), and Royal Marsden Hospital and Institute of Cancer Research, London (M.D.) — both in the United Kingdom; Sunnybrook Health Sciences Centre and the University of Toronto, Toronto (K.I.P.); Karolinska Institutet and Karolinska University Hospital, Stockholm (J. Bergh); and the University of Michigan Comprehensive Cancer Center, Ann Arbor (D.F.H.).
Address reprint requests to the EBCTCG Secretariat, Richard Doll Bldg., Old Road Campus, Oxford OX3 7LF, United Kingdom, or at email@example.com.
A complete list of the members of the Early Breast Cancer Trialist
Publisher URL: http://www.nejm.org/doi/full/10.1056/NEJMoa1701830
Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.
Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.