Chemotherapy for early breast cancer: benefits and risks in 100,000 women

Overview

Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Lancet 2023 · PMID 37061269 · DOI 10.1016/S0140-6736(23)00285-4

Anthracycline-taxane chemotherapy lowered recurrence and breast-cancer death; it caused about one extra leukaemia per 700 women and no measurable excess heart deaths within about 5 years.

Does the study support the specific claim? Partly · Methodological quality: high

Original publication

Plain-language summary

Scientific in-depth review

1. Full reference

Authors

Early Breast Cancer Trialists' Collaborative Group (EBCTCG)

Journal

Lancet

Year

2023

Identifier

PMID 37061269 DOI 10.1016/S0140-6736(23)00285-4

Verification

verified – PubMed efetch 2026-10-26 (PublicationType and CommentsCorrections checked); Crossref 2026-10-26

Retracted

no

Corrections

none

Extent checked

full text

Conflicts of interest and funding

Cancer Research UK, UK Medical Research Council; funders had no role. Several writing-committee members report industry grants/consulting (declared).

2. Research question

What are the benefits and risks of adding anthracycline to taxane chemotherapy, and how do anthracycline-taxane regimens compare?

3. Study design and population

Study design

Meta-analysis – Individual-patient-data meta-analysis of randomised trials (log-rank, intention-to-treat)

Population

Women with early-stage operable breast cancer in randomised adjuvant or neoadjuvant trials begun before 2012

Country

International (trials from North America, Europe, Asia)

Period

Trials started before 1 Jan 2012; search to Sept 2022; median follow-up 5.4 years for the main comparison

Sample size

18,103 women (15 trials, taxane with vs without anthracycline); 52,976 women (35 trials, anthracycline with vs without taxane); about 100,000 overall

Inclusion and exclusion criteria

Randomised trials of anthracycline and/or taxane regimens with mature follow-up; patient-level data supplied by trialists; nab-paclitaxel trials mostly excluded

4. Methods and endpoints

Exposure / intervention

Taxane regimen plus anthracycline (concurrent or sequential)

Comparator

Taxane regimen without anthracycline (mostly docetaxel-cyclophosphamide x6)

Endpoints

Recurrence, breast cancer mortality, death without recurrence, all-cause mortality, AML and other second cancers

Statistical methods

Stratified log-rank first-event rate ratios; 95% CI for meta-analyses, 99% CI for subgroups; breast-cancer mortality derived by subtraction

5. Actual results

Results

All 15 trials: recurrence RR 0.86 (95% CI 0.79-0.93); 10-year recurrence 16.4% vs 18.9% (ARR 2.6%, 0.9-4.2); 10-year breast cancer mortality 10.4% vs 12.0% (ARR 1.6%, 0.1-3.1); no increase in death without recurrence, including cardiovascular death. Concurrent anthracycline added to docetaxel-cyclophosphamide: 10-year recurrence 12.3% vs 21.0% (RR 0.58, 0.47-0.73), breast cancer mortality reduced by 4.2% (0.4-8.1). AML 12/6768 (0.18%) vs 2/6783 (0.03%), p=0.013 (about one extra case per 700 women). Adding taxane to same-dose anthracycline: recurrence RR 0.87 (0.82-0.93), 10-year breast cancer mortality reduced by 3.6% (1.8-5.4).

Absolute risks

10-year absolute recurrence reduction 2.6 percentage points overall (8.7 for concurrent regimens); AML +0.15 percentage points (NNH about 680)

Authors' conclusion

Anthracycline plus taxane regimens are most efficacious at reducing recurrence and death; higher cumulative doses give the greatest benefit. Treating 1000 women with anthracycline would cause one or two AML cases; no increase in cardiovascular death was seen, but follow-up was short and high cardiac-risk patients were often excluded.

6. Strengths

• Individual patient data from almost all relevant randomised trials
• Intention-to-treat; randomised comparisons
• Reports harms (AML, non-breast-cancer death) alongside benefits

7. Weaknesses

• Median follow-up only 5.4 years for the taxane +/- anthracycline comparison (late cardiac effects underestimated)
• Patients with high cardiovascular risk often excluded
• Non-fatal toxicity data available from only two trials; no quality-of-life data
• Heterogeneous regimens across trial sets (heterogeneity p=0.0009)

8. Risk of bias

Orienting tool

AMSTAR 2

Type of assessment

simplified assessment (abstract only)

Full formal assessment

no

Overall risk of bias

low

Rationale

IPD meta-analysis with comprehensive search and data checking; limitation is short follow-up for late harms, not bias in efficacy estimates.

9. Assessment of the statistical interpretation

Rate ratios are log-rank first-event ratios; absolute differences are reported with CIs. NNH for AML recomputed as about 677 (stats/C-CHM-03.py).

10. Relevance to the specific claim

Gives both sides in one randomised data set: chemotherapy benefit (fewer recurrences and deaths) and quantified harm (AML about 1 in 700; no measurable excess cardiovascular death over about 5 years).

11. Independent contrary findings

Long-term cardiotoxicity cohorts (A-CHM-01, A-CHM-03) show harms that a 5-year trial follow-up cannot capture.

12. Transferability to Germany and Europe

Directly applicable to European and Egyptian adjuvant breast cancer practice; regimens are standard internationally.

13. Overall methodological judgement

High-quality evidence that anthracycline-taxane chemotherapy reduces recurrence and breast-cancer death, with real but small absolute harms.

14. Open questions

Long-term cardiac outcomes beyond 10 years under current regimens.

15. Linked fact checks

• Anthracycline chemotherapy (and chest radiotherapy) can cause chronic, dose-dependent heart damage that may appear or progress years after treatment. – Studies with mixed or unclear results
• Chemotherapy and radiotherapy can cause second cancers (e.g., breast cancer after chest radiation for Hodgkin disease, therapy-related myeloid leukaemia) years after cure. – Studies supporting the claim
• The archive's 19 chemo/radiation studies are presented on the homepage as 'scientific studies confirming what Dr. Diaa proposed'; the harm-only study selection implies that the harms of chemotherapy and radiotherapy outweigh their benefits. – Studies contradicting or limiting the claim
• Chemotherapy and tumour-removal surgery do not address root causes; the body will reactivate its 'defensive plan' elsewhere, so these treatments should be avoided. – Studies contradicting or limiting the claim
• Cancer patients should not take chemotherapy, radiotherapy or biological therapy (or should stop them) and follow the Tayebat system instead; 'we are against the word medicine'. – Studies contradicting or limiting the claim