The Absolute Effect / Evidence / Breast Cancer
ABCSG-16 / SALSA
Clinical question: After five years of adjuvant endocrine therapy, does extending anastrozole for five rather than two additional years improve disease-free survival?
Registry: NCT00295620 · One underlying study; aliases and follow-up publications consolidated.
Phase III · randomized · Evidence cut-off: 8 November 2026Design, population and eligibility
Open-label randomized phase III trial comparing two versus five additional years of anastrozole after five years of adjuvant endocrine therapy.
3,484 randomized; intention-to-treat population 3,470 (1,732 assigned 2 years; 1,738 assigned 5 years). Primary analysis set included 3,208 disease-free at the 2-year landmark.
Postmenopausal women with hormone-receptor-positive early breast cancer who had completed five years of adjuvant endocrine therapy (tamoxifen, aromatase inhibitor or sequence).
Primary analysis after 8 years from randomization in the 3,208 patients disease-free after the first 2 years of extended therapy.
Treatment and comparator
Intervention: Anastrozole for five additional years (10 years total endocrine therapy).
Comparator: Anastrozole for two additional years (7 years total endocrine therapy).
Primary endpoint: Disease-free survival in the primary analysis set.
Key efficacy outcomes
8-year DFS: 73.9% with 5-year extension vs 73.6% with 2-year extension HR 0.99 (95% CI 0.85–1.15); p=0.90.
Clinical bone fractures: 6.3% vs 4.7% HR 1.35 (95% CI 1.00–1.84).
There was no DFS benefit from five rather than two additional years of anastrozole. The 8-year DFS absolute difference was +0.3 percentage points, HR 0.99, p=0.90.
Absolute outcome visualization
Eight-year DFS and clinical fracture incidence.
Bars show source-reported endpoint values; no outcomes are reconstructed from median survival. Single-arm outcomes are not comparative effects.
NNT / NNH
No NNT: no improvement in DFS was demonstrated (HR 0.99; p=0.90).
The 1.6-point absolute increase in clinical fractures with the longer extension corresponds to a crude NNH of approximately 63 over the reported analysis period; HR 1.35 (95% CI 1.00–1.84), so precision is borderline and should be interpreted cautiously.
Toxicity, grade 3–5 harms and treatment burden
Clinical bone fractures occurred in 6.3% with five additional years versus 4.7% with two additional years. The trial supports attention to skeletal health when considering prolonged aromatase inhibition.
The longer strategy adds three years of daily endocrine treatment, monitoring, adherence burden and cumulative musculoskeletal/bone exposure without improving DFS in the overall study population.
Quality of life
No global QoL superiority is claimed. Longer aromatase-inhibitor exposure can affect arthralgia, bone health and daily treatment burden.
Subgroups and applicability
No subgroup showed a convincing differential DFS benefit in the reported analysis. Individual residual recurrence risk and tolerability remain relevant to duration decisions.
Limitations
Primary analysis is landmark-based among patients disease-free after two years of extended therapy; 14 randomized patients lacked signed consent and were excluded from ITT. The result does not imply that no high-risk individual can benefit from longer therapy.
Clinical interpretation
SALSA argues against routine extension to ten total years for every postmenopausal patient. Two additional years achieved similar DFS to five additional years, with fewer fractures.
Contemporary-practice note (8 November 2026): historical trial efficacy is distinguished from present-day treatment selection. Comprehensive guideline-level freshness review remains pending for this batch; apply current disease-specific guidance and multidisciplinary context.
Primary sources and related publications
Missing values are not imputed; meeting abstracts are identified as such.