Show simple item record

dc.contributor.authorEarly Breast Cancer Trialists’ Collaborative group (EBCTCG)
dc.identifier.citationThe Lancet. Oncology, 2021, 22 (8), pp. 1139 - 1150en_US
dc.description.abstract<h4>Background</h4>Trastuzumab targets the extracellular domain of the HER2 protein. Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces the risk of recurrence and death, but is associated with cardiac toxicity. We investigated the long-term benefits and risks of adjuvant trastuzumab on breast cancer recurrence and cause-specific mortality.<h4>Methods</h4>We did a collaborative meta-analysis of individual patient data from randomised trials assessing chemotherapy plus trastuzumab versus the same chemotherapy alone. Randomised trials that enrolled women with node-negative or node-positive, operable breast cancer were included. We collected individual patient-level data on baseline characteristics, dates and sites of first distant breast cancer recurrence and any previous local recurrence or second primary cancer, and the date and underlying cause of death. Primary outcomes were breast cancer recurrence, breast cancer mortality, death without recurrence, and all-cause mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, oestrogen receptor (ER) status, and trial yielded first-event rate ratios (RRs).<h4>Findings</h4>Seven randomised trials met the inclusion criteria, and included 13 864 patients enrolled between February, 2000, and December, 2005. Mean scheduled treatment duration was 14·4 months and median follow-up was 10·7 years (IQR 9·5 to 11·9). The risks of breast cancer recurrence (RR 0·66, 95% CI 0·62 to 0·71; p<0·0001) and death from breast cancer (0·67, 0·61 to 0·73; p<0·0001) were lower with trastuzumab plus chemotherapy than with chemotherapy alone. Absolute 10-year recurrence risk was reduced by 9·0% (95% CI 7·4 to 10·7; p<0·0001) and 10-year breast cancer mortality was reduced by 6·4% (4·9 to 7·8; p<0·0001), with a 6·5% reduction (5·0 to 8·0; p<0·0001) in all-cause mortality, and no increase in death without recurrence (0·4%, -0·3 to 1·1; p=0·35). The proportional reduction in recurrence was largest in years 0-1 after randomisation (0·53, 99% CI 0·46 to 0·61), with benefits persisting through years 2-4 (0·73, 0·62 to 0·85) and 5-9 (0·80, 0·64 to 1·01), and little follow-up beyond year 10. Proportional recurrence reductions were similar irrespective of recorded patient and tumour characteristics, including ER status. The more high risk the tumour, the larger the absolute reductions in 5-year recurrence (eg, 5·7% [95% CI 3·1 to 8·3], 6·8% [4·7 to 9·0], and 10·7% [7·7 to 13·6] in N0, N1-3, and N4+ disease).<h4>Interpretation</h4>Adding trastuzumab to chemotherapy for early-stage, HER2-positive breast cancer reduces recurrence of, and mortality from, breast cancer by a third, with worthwhile proportional reductions irrespective of recorded patient and tumour characteristics.<h4>Funding</h4>Cancer Research UK, UK Medical Research Council.en_US
dc.format.extent1139 - 1150en_US
dc.subjectEarly Breast Cancer Trialists’ Collaborative group (EBCTCG)en_US
dc.subjectBreast Neoplasmsen_US
dc.subjectReceptor, erbB-2en_US
dc.subjectAntineoplastic Agents, Immunologicalen_US
dc.titleTrastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials.en_US
dc.typeJournal Article
dc.relation.isPartOfThe Lancet. Oncologyen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.embargo.termsNot knownen_US
icr.researchteamClinical Trials & Statistics Unit
dc.contributor.icrauthorBliss, Judithen_US

Files in this item


This item appears in the following Collection(s)

Show simple item record
Except where otherwise noted, this item's license is described as