MammaPrint Predicts Chemotherapy Benefit in HR+HER2- Early Breast Cancer: FLEX Registry Real-World Data.

Document Type

Article

Publication Date

9-1-2025

Publication Title

JNCI Cancer Spectrum

Abstract

BACKGROUND: Gene expression assays help personalize adjuvant chemotherapy decisions for hormone receptor-positive, HER2-negative (HR+HER2-) early breast cancer (EBC). The 70-gene risk of distant-recurrence signature, MammaPrint, demonstrated clinical utility in guiding chemotherapy de-escalation in genomically low risk patients in the MINDACT trial. This study evaluates MammaPrint as a continuous predictor of chemotherapy benefit in HR+HER2- EBC using real-world data (RWD) from the FLEX Registry.

METHODS: The study evaluated 1002 patients treated with endocrine therapy (ET) only or ET with chemotherapy (ET+CT) enrolled in FLEX (NCT03053193) with 5-year median follow-up. Propensity-score matching balanced treatment groups by menopausal status, T-stage, and nodal status. The primary endpoint was distant recurrence-free interval (DRFI). Regression and Cox proportional hazards models assessed chemotherapy benefit across MammaPrint Index (MPI) risk.

RESULTS: Most patients were postmenopausal (70.1%), node-negative (70.0%), and had grade 2 tumors (51.2%). The regression models showed that MPI strongly predicted 5-year DRFI in ET only (R2 = 0.99, P <  .001) and ET + CT (R2 = 0.90, P <  .001) groups, corresponding to an average absolute chemotherapy benefit of 5.6% in High 1 and 10.9% in High 2. Minimal improvement in DRFI with chemotherapy was observed for Low (1.7%) and UltraLow (< 1.0%) risk groups. A multivariate Cox model with an MPI-by-treatment interaction term demonstrated that increasing MPI risk was associated with greater chemotherapy benefit on DRFI (HR = 0.15, P = .047). Chemotherapy benefit was significantly associated with premenopausal status, but not age, T-stage, nodal status, or grade.

CONCLUSIONS: These RWD from the FLEX Registry demonstrate that MPI is predictive of both DRFI prognosis and chemotherapy benefit in HR+HER2- EBC. (NCT03053193).

Volume

9

Issue

5

First Page

pkaf079

Last Page

pkaf079

DOI

10.1093/jncics/pkaf079

ISSN

2515-5091

PubMed ID

40796181

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