The Absolute Effect / Evidence / MINDACT
MINDACT
In early breast cancer with discordant clinical and genomic risk, can the 70-gene MammaPrint signature identify patients who may omit adjuvant chemotherapy without an unacceptable loss of distant metastasis-free survival?
Registry: NCT00433589 · One underlying randomized study; aliases and follow-up reports consolidated.
Design, population and eligibility
Prospective, multicentre, phase III randomized strategy trial; 6,693 patients enrolled.
Clinical-high/genomic-low risk cohort randomized to chemotherapy or no chemotherapy; 1,497 patients in the randomized comparison.
Operable early breast cancer; clinical risk by modified Adjuvant! Online and genomic risk by 70-gene signature; HR-positive/HER2-negative subgroup analyses prespecified.
Primary 5-year analysis followed by 8-year DMFS and 2026 exploratory subgroup publications.
Treatment and comparator
Adjuvant chemotherapy followed by endocrine therapy as indicated in clinical-high/genomic-low risk patients.
No chemotherapy; endocrine therapy and other indicated local treatment maintained.
Primary endpoint: Five-year distant metastasis-free survival (DMFS) in the clinical-high/genomic-low group; subsequent eight-year follow-up.
Other endpoints: Overall survival, DFS, chemotherapy interaction by age and tumour biology.
Key efficacy results
At five years, DMFS without chemotherapy was 94.7%, meeting the prespecified non-inferiority boundary in the clinical-high/genomic-low group.
At eight years, DMFS was 92.0% with chemotherapy versus 89.4% without chemotherapy; HR 0.66 (95% CI 0.48–0.92). The absolute difference was 2.6 percentage points in favour of chemotherapy.
In HR-positive/HER2-negative patients, the exploratory age interaction suggested a larger absolute chemotherapy benefit in women aged ≤50 years (approximately 5.0 points) than in women aged >50 years (approximately 0.2 points).
A 2026 exploratory analysis of 868 women >50 years (median follow-up 8.7 years) reported no-chemotherapy 8-year DMFS of 87.9% for tumours >2 cm, 91.3% for grade 3 tumours and 89.6% for 1–3 involved nodes. The absolute 8-year DMFS benefit from chemotherapy in these strata was +1.2%, −2.2% and +0.7%, respectively. These exploratory estimates do not define new randomized treatment groups.
Source-reported outcome visualization
Eight-year distant metastasis-free survival · 8 years · randomized clinical-high/genomic-low cohort
Kaplan–Meier estimates from the eight-year update. This is a modest absolute difference despite a statistically significant HR.
Absolute effect
The eight-year absolute DMFS difference was 2.6 percentage points (92.0% versus 89.4%). Reciprocal NNT ≈39 at eight years for the full randomized clinical-high/genomic-low cohort; interpret cautiously because the trial's primary non-inferiority strategy and age interaction are central to treatment selection.
NNT: Approximately 39 at eight years for DMFS in the overall randomized clinical-high/genomic-low group; age-specific effects differ and should not be generalized.
NNH: Not calculated: chemotherapy toxicity is regimen- and age-dependent, and a single comparable fixed-horizon grade ≥3 toxicity rate is not supplied by the cited primary follow-up.
Toxicity, harms and treatment burden
Chemotherapy adds acute myelosuppression, infection risk, alopecia, nausea, fatigue and regimen-specific neuropathy/cardiotoxicity; late effects depend on regimen and age.
The decision to omit chemotherapy avoids treatment burden but does not eliminate endocrine therapy, radiotherapy or surveillance.
No composite grade 3–5 harm or treatment-discontinuation NNH is assigned without a source-matched fixed-horizon denominator.
Quality of life and patient-reported outcomes
The clinical utility of genomic testing includes avoiding chemotherapy in selected patients; however, patient-reported outcomes and decisional regret should be taken from dedicated MINDACT QoL analyses rather than inferred from DMFS.
Subgroups, maturity and limitations
The apparent age interaction in HR-positive/HER2-negative disease is clinically important; chemotherapy benefit in younger women may partly reflect ovarian function suppression.
The 2026 subgroup analysis is exploratory; small absolute subgroup differences with wide uncertainty should not be treated as definitive predictive validation.
The genomic assay is a treatment-decision tool in the trial's defined population, not a universal replacement for clinicopathological assessment or other validated assays.
Clinical interpretation
Current-practice context · 1 November 2026 (full guideline freshness review pending): Use validated genomic assays only in the clinical populations and decision settings supported by current guidelines. Integrate menopausal status, nodal burden, tumour biology, ovarian suppression options and patient preference.
Primary sources and registry
- Piccart et al. Lancet Oncology 2021 (8-year MINDACT update)
- MINDACT 2026 subgroup publication
- ClinicalTrials.gov NCT00433589
Source hierarchy: primary randomized report and prespecified follow-up first. Missing numerical toxicity, discontinuation or QoL data are labelled rather than imputed.