Women with early-stage oestrogen receptor (ER)-positive (ER+) breast cancer who receive standard endocrine therapy for 5 years remain at risk of distant recurrence for at least 15 years after treatment discontinuation. The extension of the duration of adjuvant endocrine therapy to 10 years has been shown to reduce the risk of recurrence only in a subset of women and, to date, predictive biomarkers of benefit from therapy do not exist. In this Review, we briefly explore the epidemiology of late recurrence (>5 years after diagnosis) in patients with ER+ breast cancer. The mechanisms underlying this phenomenon remain poorly understood; we discuss the evidence currently available on processes such as alterations of gene expression or specific genomic aberrations and examine several models used for risk prognostication and for estimating the presence of minimal residual disease, as well as the relevance of these prediction tools for clinicians and patients. Our aim is to enable clinicians to make well-informed decisions on whether to extend endocrine therapy for each individual patient.
Oestrogen receptor (ER)-positive (ER+) breast cancer is at least as likely to recur beyond 5 years as it is before 5 years from diagnosis.
Extended endocrine therapy is likely to improve survival in a subgroup of women with ER+ breast cancer; all women should be evaluated for their likely risk of recurrence at the completion of 5 years of endocrine therapy.
Clinical and genomic expression models can help stratify patients for their risk of late recurrence, but most are not predictive of benefit from extended endocrine therapy.
Dormancy of ER+ breast cancer occurs through a multitude of mechanisms; microscopic disease can emerge from dormancy in some women in response to unidentified triggers.
Monitoring of minimal residual disease through circulating tumour cells and circulating tumour DNA is likely to prove beneficial for anticipating late recurrence.
An individualized, patient-centred approach to long-term risk management is essential owing to the protracted length of survivorship and its ensuing complexity.
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J.R. is a Cridlan Ross Smith Charitable Trust clinical research fellow. The authors acknowledge support from the UK National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. The authors are thankful to C. Isacke and A. Ring for providing internal review and feedback on this manuscript.
Nature Reviews Clinical Oncology thanks J. Cortes, G. Viale and the other anonymous reviewer(s) for their contribution to the peer review of this work.
The authors declare no competing interests.
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Richman, J., Dowsett, M. Beyond 5 years: enduring risk of recurrence in oestrogen receptor-positive breast cancer. Nat Rev Clin Oncol 16, 296–311 (2019). https://doi.org/10.1038/s41571-018-0145-5
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