Messaggi chiave
- IDEAL è uno studio randomizzato di fase III in cui pazienti in post-menopausa con carcinoma mammario precoce (eBC) HR+ sono state assegnate a ricevere 2,5 o 5 anni di letrozolo dopo gli iniziali cinque anni di ormonoterapia. Viene qui presentata un’analisi secondaria dello studio che si è proposta di indagare la capacità del test Mammaprint di predire quali pazienti potrebbero trarre beneficio da un prolungamento della terapia endocrina (EET) di 5 vs 2,5 anni.
- Lo studio ha incluso un totale di 515 donne. Di queste, 223 (43,3%) con tumori classificati come a basso rischio hanno ottenuto un beneficio assoluto del 10,1% in termini di recidiva a distanza (DR) (hazard ratio, 0,32; IC 95%, 0,12-0,87; p = 0,03), sebbene con un test di interazione del trattamento non significativo. Nelle pazienti con tumori ad alto rischio (259 [50,3%]) o a rischio ultrabasso (33 [6,4%]), 5 rispetto a 2,5 anni di EET non hanno prodotto alcun miglioramento del beneficio in DR. Come previsto, i tassi di eventi avversi e interruzioni del trattamento sono stati paragonabili nei diversi gruppi di rischio all’interno di ciascun braccio di trattamento.
- Gli autori concludono che, oltre a guidare le decisioni relative alla chemioterapia neo(adiuvante), il test Mammaprint potrebbe fornire informazioni utili a stabilire la durata ottimale della terapia endocrina in pazienti con eBC HR+.
Abstract
Importance
- There is a need for biomarkers that predict late recurrence risk and extended endocrine therapy (EET) benefit among patients with early-stage breast cancer (EBC).
- MammaPrint, a 70-gene expression risk-of-recurrence assay, has been found to project significant EET benefit in patients with assay-classified low-risk tumors.
Objective
- To determine the test’s utility in identifying which patients with EBC in the IDEAL (Investigation on the Duration of Extended Adjuvant Letrozole) trial could benefit from 5-year vs 2.5-year letrozole treatment.
Design, setting, and participants
- This secondary analysis of the IDEAL randomized clinical trial evaluated postmenopausal women with hormone receptor-positive EBC who were assigned to either 2.5 or 5 years of EET, with 10 years of follow-up after randomization.
- A 70-gene assay was used to classify tumors as high, low, or ultralow risk.
- Adverse event (AE) frequency and treatment compliance were evaluated.
- Statistical analyses were performed from April 2022 to September 2024.
Interventions
- After 5 years of endocrine therapy, patients were randomized to 2.5 or 5 years of EET with letrozole.
Main outcomes and measures
- Primary end point was distant recurrence (DR).
- Cox proportional hazard regression models and likelihood ratios tested the interaction between treatment and gene expression assay.
Results
- Among 515 women included (mean [SD] age at randomization, 59.9 [9.5] years), 265 were in the 2.5-year treatment arm and 250 in the 5-year treatment arm.
- Of these patients, 223 (43.3%) patients with 70-gene assay-classified low-risk tumors had a significant absolute benefit of 10.1% for DR (hazard ratio, 0.32; 95% CI, 0.12-0.87; p = 0.03).
- Treatment interaction was not significant for DR.
- Of patients with either 70-gene assay-classified high-risk tumors (259 [50.3%]) or ultralow risk tumors (33 [6.4%]), 5 years vs 2.5 years of EET was not associated with improved benefit for DR.
- As expected, rates of AEs and treatment discontinuation were comparable among the different 70-gene assay risk groups in each treatment arm.
Conclusions and relevance
- This secondary analysis of the IDEAL trial found that the 70-gene assay identified patients with low-risk tumors who could benefit from 5-year vs 2.5-year EET.
- These findings suggest that this gene expression assay could go beyond guiding neoadjuvant and adjuvant chemotherapy decisions to informing the optimal duration of adjuvant endocrine therapy.