The Absolute Effect / Evidence / NSABP B-42
NSABP B-42
In postmenopausal women with hormone-receptor-positive early breast cancer who remain disease-free after five years of endocrine therapy, does extended letrozole improve disease-free survival compared with placebo?
Trial registry: NCT00382070 · One underlying study; follow-up publications consolidated.
Design, population and eligibility
Double-blind, placebo-controlled phase III randomized trial.
3,966 postmenopausal women; stage I–IIIA hormone-receptor-positive breast cancer.
Disease-free after five years of AI-based endocrine therapy or tamoxifen for no more than three years followed by an AI; prior surgery and indicated local treatment completed.
Ten-year update; median follow-up approximately 10.3 years.
Treatment and comparator
Letrozole 2.5 mg orally once daily for five additional years.
Placebo once daily for five years.
Primary endpoint: DFS: recurrence, second primary malignancy or death as defined by protocol.
Other endpoints: OS, breast cancer-free interval, distant recurrence, osteoporotic fractures and arterial thrombotic events.
Key efficacy results
Ten-year DFS was 75.9% with letrozole versus 72.6% with placebo; HR 0.85 (95% CI 0.74–0.96), P=0.01.
Ten-year OS was not improved: HR 0.97 (95% CI 0.82–1.15), P=0.74.
Ten-year absolute reductions in breast cancer-free interval events and distant recurrence were reported; no significant increase in osteoporotic fractures or arterial thrombotic events was observed in the 10-year update.
Source-reported outcome visualization
Ten-year disease-free survival · 10 years
Ten-year Kaplan–Meier estimates from the prespecified long-term update.
Absolute effect
Absolute ten-year DFS improvement was 3.3 percentage points. Approximate NNT = 30 over ten years (1/0.033), endpoint DFS. There was no OS benefit.
NNT: Approximately 30 over ten years to prevent one DFS event, using the reported fixed-time DFS estimates.
NNH: Not quantifiable from the reported fracture/arterial-event comparison because no significant excess was demonstrated and a single toxicity endpoint NNH is not justified.
Toxicity, harms and treatment burden
The long-term update did not identify a significant increase in osteoporotic fractures or arterial thrombotic events; this does not remove the need to assess bone health and vascular risk.
The trial included treatment burden of five additional years of daily endocrine therapy, including arthralgia, vasomotor symptoms and adherence burden.
No statistically significant OS improvement was seen. Do not imply a survival benefit from the DFS result.
Quality of life and patient-reported outcomes
Quality-of-life and symptom burden should be weighed against a modest absolute DFS gain. The ten-year update did not establish a broad QoL advantage; numerical QoL effects should be taken from the dedicated patient-reported outcome publication if included.
Subgroups, maturity and limitations
Benefit in DFS was observed across several prespecified strata; absolute benefit varies with baseline recurrence risk.
The population had already tolerated and completed five years of endocrine therapy, limiting generalizability to patients with substantial prior toxicity or poor adherence.
B-42 is distinct from MA.17 and MA.17R; do not combine their denominators or treatment histories.
Clinical interpretation
Current-practice context · 1 November 2026 (full guideline freshness review pending): Extended AI therapy is not automatic for every patient. Consider nodal status, tumour size/grade, prior treatment, late-recurrence risk, bone density, competing mortality and patient preference.
Primary sources and registry
Source hierarchy: primary randomized report and prespecified follow-up first; registry and current guidance are supplementary. Values not reported in the cited primary sources are explicitly marked unavailable rather than imputed.