Journal Article
. 2017 Oct; 18(11):1502-1511.
doi: 10.1016/S1470-2045(17)30600-9.

Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial

Vivianne C G Tjan-Heijnen 1 Irene E G van Hellemond 2 Petronella G M Peer 3 Astrid C P Swinkels 4 Carolien H Smorenburg 5 Maurice J C van der Sangen 6 Judith R Kroep 7 Hiltje De Graaf 8 Aafke H Honkoop 9 Frans L G Erdkamp 10 Franchette W P J van den Berkmortel 11 Maaike de Boer 2 Wilfred K de Roos 12 Sabine C Linn 13 Alexander L T Imholz 14 Caroline M Seynaeve 15 Dutch Breast Cancer Research Group (BOOG) for the DATA Investigators  
  • PMID: 29031778
  •     25 citations


Background: The effect of extended adjuvant aromatase inhibition in hormone receptor-positive breast cancer after sequential endocrine therapy of tamoxifen followed by an aromatase inhibitor for a 5-year treatment period still needs clarification. To address this issue, we began the DATA study to assess different durations of anastrozole therapy after tamoxifen.

Methods: DATA was a prospective, randomised, open-label, multicentre, phase 3 study done in 79 hospitals in the Netherlands. We randomly assigned postmenopausal women with hormone receptor-positive early breast cancer with no signs of disease recurrence after 2-3 years of adjuvant tamoxifen to either 3 or 6 years of anastrozole treatment (1 mg orally once a day) in a 1:1 ratio. We used TENALEA (Trans European Network for Clinical Trials Services) for the randomisation procedure. Stratification factors were nodal status, hormone receptor status, HER2 status, and tamoxifen treatment duration. The primary study endpoint of this analysis was disease-free survival starting beyond 3 years after randomisation (adapted disease-free survival). Here we report the final analysis from the DATA trial, which is registered with, number NCT00301457.

Findings: Between June 28, 2006, and Aug 10, 2009, we screened 1912 patients of whom 955 were assigned to the 3-year group and 957 to the 6-year anastrozole treatment group. 1860 patients were eligible (931 in the 6-year group and 929 in the 3-year group) and 1660 were disease free 3 years after randomisation. The 5-year adapted disease-free survival was 83·1% (95% CI 80·0-86·3) in the 6-year group and 79·4% (76·1-82·8) in the 3-year group (hazard ratio [HR] 0·79 [95% CI 0·62-1·02]; p=0·066). Patients in the 6-year treatment group had more adverse events than those in the 3-year treatment group, including all-grade arthralgia or myalgia (478 [58%] of 827 in the 6-year treatment group vs 438 [53%] of 833 in the 3-year treatment group) and osteopenia or osteoporosis (173 [21%] vs 137 [16%]).

Interpretation: We cannot recommend the use of extended adjuvant aromatase inhibition after 5 years of sequential endocrine therapy in all postmenopausal women with hormone receptor-positive breast cancer.

Funding: AstraZeneca.

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.
Hongchao Pan, Richard Gray, +9 authors, EBCTCG.
N Engl J Med, 2017 Nov 09; 377(19). PMID: 29117498    Free PMC article.
Highly Cited.
Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.
Ivana Sestak, Richard Buus, +9 authors, Mitch Dowsett.
JAMA Oncol, 2018 Feb 17; 4(4). PMID: 29450494    Free PMC article.
Highly Cited.
Current Status of Extended Adjuvant Endocrine Therapy in Early Stage Breast Cancer.
Irene E G van Hellemond, Sandra M E Geurts, Vivianne C G Tjan-Heijnen.
Curr Treat Options Oncol, 2018 Apr 29; 19(5). PMID: 29704066    Free PMC article.
Endocrine therapy for breast cancer in the primary care setting.
A Awan, K Esfahani.
Curr Oncol, 2018 Aug 17; 25(4). PMID: 30111969    Free PMC article.
Extended duration of adjuvant aromatase inhibitor in breast cancer: a meta-analysis of randomized controlled trials.
Zackariah Clement, James Kollias, +2 authors, Melissa Bochner.
Gland Surg, 2018 Dec 07; 7(5). PMID: 30505766    Free PMC article.
Assessment and management of bone health in women with early breast cancer receiving endocrine treatment in the DATA study.
Irene E G van Hellemond, Carolien H Smorenburg, +14 authors, Dutch Breast Cancer Research Group (BOOG).
Int J Cancer, 2019 Feb 13; 145(5). PMID: 30748011    Free PMC article.
Incidence of Late Relapses in Patients With HER2-Positive Breast Cancer Receiving Adjuvant Trastuzumab: Combined Analysis of NCCTG N9831 (Alliance) and NRG Oncology/NSABP B-31.
Saranya Chumsri, Zhuo Li, +9 authors, E Aubrey Thompson.
J Clin Oncol, 2019 Oct 18; 37(35). PMID: 31622131    Free PMC article.
The trans-DATA study: aims and design of a translational breast cancer prognostic marker identification study.
Tim C de Ruijter, Kim M Smits, +7 authors, Vivianne C G Tjan-Heijnen.
Diagn Progn Res, 2019 Oct 24; 3. PMID: 31641693    Free PMC article.
Aromatase inhibitors and risk of cardiovascular events in breast cancer patients: a systematic review and meta-analysis.
Yang He, Jianhua Zhang, +5 authors, Dongsheng Hong.
BMC Pharmacol Toxicol, 2019 Oct 31; 20(1). PMID: 31665091    Free PMC article.
Systematic Review.
Endocrine-responsive lobular carcinoma of the breast: features associated with risk of late distant recurrence.
Fabio Conforti, Laura Pala, +12 authors, Aron Goldhirsch.
Breast Cancer Res, 2020 Jan 01; 21(1). PMID: 31888717    Free PMC article.
Efficacy of anastrozole after tamoxifen in early breast cancer patients with chemotherapy-induced ovarian function failure.
Irene E G van Hellemond, Ingeborg J H Vriens, +15 authors, Dutch Breast Cancer Research Group (BOOG).
Int J Cancer, 2018 Dec 28; 145(1). PMID: 30588619    Free PMC article.
Association of Industry and Academic Sponsorship With Negative Phase 3 Oncology Trials and Reported Outcomes on Participant Survival: A Pooled Analysis.
Alfredo Addeo, Glen J Weiss, Bishal Gyawali.
JAMA Netw Open, 2019 May 11; 2(5). PMID: 31074821    Free PMC article.
Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial.
Irene E G van Hellemond, Carolien H Smorenburg, +14 authors, Dutch Breast Cancer Research Group (BOOG).
Breast Cancer Res Treat, 2020 Mar 04; 180(3). PMID: 32124136    Free PMC article.
Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial.
Eleftherios P Mamounas, Hanna Bandos, +17 authors, Norman Wolmark.
Lancet Oncol, 2018 Dec 05; 20(1). PMID: 30509771    Free PMC article.
Natural history of luminal A breast invasive ductal carcinoma in an elderly.
Geok Hoon Lim, Samantha Piao Xue Tay, Mihir Gudi.
BMJ Case Rep, 2018 Apr 19; 2018. PMID: 29666097    Free PMC article.
Toronto Workshop on Late Recurrence in Estrogen Receptor-Positive Breast Cancer: Part 1: Late Recurrence: Current Understanding, Clinical Considerations.
Ryan J O Dowling, Kevin Kalinsky, +29 authors, Pamela J Goodwin.
JNCI Cancer Spectr, 2020 Apr 28; 3(4). PMID: 32337479    Free PMC article.
Management of hormone receptor-positive, HER2-negative early breast cancer.
Elaine M Walsh, Karen L Smith, Vered Stearns.
Semin Oncol, 2020 Jun 18; 47(4). PMID: 32546323    Free PMC article.
Endocrine Therapy in Early Breast Cancer.
Katja Krauss, Elmar Stickeler.
Breast Care (Basel), 2020 Sep 29; 15(4). PMID: 32982643    Free PMC article.
Do we still need breast cancer screening in the era of targeted therapies and precision medicine?
Rubina Manuela Trimboli, Paolo Giorgi Rossi, +4 authors, Francesco Sardanelli.
Insights Imaging, 2020 Sep 26; 11(1). PMID: 32975658    Free PMC article.
Landmark trials in the medical oncology management of early stage breast cancer.
Whitney Hensing, Cesar A Santa-Maria, Lindsay L Peterson, Jennifer Y Sheng.
Semin Oncol, 2020 Sep 17; 47(5). PMID: 32933761    Free PMC article.
Development of a Prognostic Tool to Guide the Decision to Extend Adjuvant Aromatase Inhibitors for up to Ten Years in Postmenopausal Early Breast Cancer Patients.
Camille Moreau-Bachelard, Loïc Campion, +6 authors, Jean-Sébastien Frénel.
Cancers (Basel), 2020 Dec 17; 12(12). PMID: 33322473    Free PMC article.
Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis.
Elizabeth M Salvo, Abril Oliva Ramirez, +4 authors, Imtiaz A Samjoo.
Breast, 2021 Mar 08; 57. PMID: 33677313    Free PMC article.
The frequency of medical reversals in a cross-sectional analysis of high-impact oncology journals, 2009-2018.
Alyson Haslam, Jennifer Gill, +5 authors, Vinay Prasad.
BMC Cancer, 2021 Aug 05; 21(1). PMID: 34344325    Free PMC article.
Can We Use Survival Data from Cancer Registries to Learn about Disease Recurrence? The Case of Breast Cancer.
Angela B Mariotto, Zhaohui Zou, +3 authors, Ruth Etzioni.
Cancer Epidemiol Biomarkers Prev, 2018 Oct 20; 27(11). PMID: 30337342    Free PMC article.
Preventive drug therapy and contralateral breast cancer: summary of the evidence of clinical trials and observational studies.
Annet Bens, Rikke Langballe, +3 authors, Lene Mellemkjaer.
Acta Oncol, 2019 Aug 09; 58(11). PMID: 31393200    Free PMC article.