Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor–positive breast cancer: ATLAS, a randomised trial
Open accessAbstract
Background For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years.Methods In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633.Findings Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%).Interpretation For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis.Funding Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.
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Taking the full course of adjuvant hormonal therapy (daily for at least five years) is necessary to obtain its full benefits.
“Adherence to the full course of treatment (one pill every day for at least 5 years) is necessary to obtain the full benefits of hormonal treatment.4, 5”
From Behavioral interventions to enhance adherence to hormone therapy in breast cancer survivors: a systematic literature review (2016) · cites this paper as [4]
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- Authors
- Davies, C., Pan, H., Godwin, J., Gray, R., Arriagada, R., Raina, V., Abraham, M., Alencar, V. H. M., Badran, A., Bonfill, X., Bradbury, J., Clarke, M., Collins, R., Davis, S. R., Delmestri, A., Forbes, J. F., Haddad, P., Hou, M.-F., Inbar, M., Khaled, H., Kielanowska, J., Kwan, W.-H., Mathew, B. S., Mittra, I., Müller, B., Nicolucci, A., Peralta, O., Pernas, F., Petruzelka, L., Pienkowski, T., Radhika, R., Rajan, B., Rubach, M. T., Tort, S., Urrútia, G., Valentini, M., Wang, Y., & Peto, R.
- Affiliations
- University of Oxford (GB)
- Glasgow Caledonian University (GB)
- Institut Gustave Roussy (FR)
- DR. B.R.A. Institute Rotary Cancer Hospital (IN)
- Instituto Cardiovascular de Rosario (AR)
- Hospital Haroldo Juaçaba (BR)
- Cairo University (EG)
- Institut de Recerca Sant Pau (ES)
- Monash University (AU)
- Breast Cancer Trials (AU)
- Tehran University of Medical Sciences (IR)
- Kaohsiung Medical University Chung-Ho Memorial Hospital (TW)
- Tel Aviv Sourasky Medical Center (IL)
- The Maria Sklodowska-Curie National Research Institute of Oncology (PL)
- Regional Cancer Center, Thiruvananthapuram (IN)
- Tata Memorial Hospital (IN)
- Mario Negri Sud Foundation (IT)
- Charles University (CZ)
- Cancer Institute (WIA) (IN)
- Royal Hospital (OM)
- Corresponding author
- Davies, Christina
- ORCID
- Pan, Hongchao
- Godwin, Jon
- Gray, Richard
- Arriagada, Rodrigo
- Bonfill, Xavier
- Collins, Rory
- Davis, Susan R
- Delmestri, Antonella
- Forbes, John F
- Haddad, Peiman
- Hou, Ming-Feng
- Khaled, Hussein
- Kwan, Wing-Hong
- Mittra, Indraneel
- Müller, Bettina
- Nicolucci, Antonio
- Peralta, Octavio
- Petruzelka, Lubos
- Rubach, Maryna T
- Urrútia, Gerard
- Wang, Yaochen
- Peto, Richard
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 381
- Issue
- 9869
- Pages
- 805-816
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC3596060
- OpenAlex
- W2161977537
- Cited by
- 2,044
- References
- 21
- Citations by year
- 2026: 74 · 2025: 99 · 2024: 125 · 2023: 144 · 2022: 143 · 2021: 162 · 2020: 134 · 2019: 140 · 2018: 155 · 2017: 198 · 2016: 191 · 2015: 202 · 2014: 155 · 2013: 118 · 2012: 2
- FWCI
- 50.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Lancet (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Figshare (submittedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- Cancer Research UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- tamoxifen, estrogen receptor-positive breast cancer, adjuvant endocrine therapy, breast cancer recurrence, breast cancer mortality, all-cause mortality, secondary malignancies, treatment side effects, long-term follow-up, ATLAS trial, early breast cancer
- MeSH terms
- Adult, Aged, Breast Neoplasms, Female, Humans, Middle Aged, Receptors, Estrogen, Tamoxifen, Time Factors, Chemotherapy, Adjuvant, Antineoplastic Agents, Hormonal
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