The FLEX study supports prediction of chemotherapy benefit by MammaPrint® in patients with HR+HER2- early-stage breast cancer

Brufsky A, et al. JNCI Cancer Spectrum. 2025.

The FLEX study supports prediction of chemotherapy benefit by MammaPrint® in patients with HR+HER2- early-stage breast cancer

Brufsky A, et al. JNCI Cancer Spectrum. 2025.

Study Findings

  • In this Real-World Evidence (RWE) prospective, propensity score matched study of 1002 patients, those with increasing \ MammaPrint Index risk (High Risk) had significantly lower risk of Distant Recurrence Free Interval (DRFI) events when treated with ET+CT (endocrine therapy+chemotherapy) compared to ET only.
  • These RWE confirm MammaPrint’s comprehensive utility, as prognostic of recurrence risk and predictive of CT benefit for patients with HR+HER2- early-stage breast cancer.
  • Consistent with findings from MINDACT, patients with MammaPrint indices within Low and UltraLow Risk ranges did not derive significant CT benefit.
  • Chemotherapy benefit is not predicted by higher tumor grade after adjusting for MammaPrint Index and clinical factors.
  • Observed CT benefit in premenopausal patients with MammaPrint Low Risk tumors may be due to ovarian function suppression.1

Study Details

  • The study is based on 1002 patients with HR+HER2- tumors from FLEX who were treated with either ET only (N=501) or ET+CT (N=501) with 5-year DRFI outcomes and propensity score matched for menopausal status, tumor stage and nodal status.
  • Kaplan Meier analysis estimated DRFI2 as a DRFI as a function of the continuous MammaPrint Index for each treatment group, with predicted 95% confidence intervals (CIs). Cox proportional hazards model was used to test for interaction between CT treatment and genomic and clinical variables. P-values of <0.05 were considered significant.

CLINICAL CHARACTERISTICS

Clinical characteristics

Differences in clinical characteristics were assessed using Student’s t-test, Chi-squared or Fisher’s Exact Test. Unknown variables were excluded.

MULTIVARIATE ANALYSIS

Hazards Ratio (HR) presented as HR (95% Confidence Interval)

WHAT IS FLEX

The FLEX study (NCT03053193) is a prospective real-world data (RWD) study focused on breast cancer, integrating full genomic profiling through MammaPrint and BluePrint with comprehensive clinical data. Its primary objective is to gather genomic and clinical information from 30,000 breast cancer patients and monitor them for over 10 years. This study is inclusive of both men and women diagnosed with stage I, II, or III breast cancer across all clinical subtypes, ensuring a representative dataset that encompasses various ethnicities, ages, genders, and health statuses. FLEX aims to facilitate research into differences and trends among breast cancer patients, particularly targeting smaller, diverse demographics that are often underrepresented in clinical trials. The study has enrolled over 20,000 patients, making it the largest, most diverse, single tumor registry of its kind. Currently data from FLEX has supported over 100 investigator initiated studies and has contributed to 6 peer-reviewed publications and over 54 abstracts at international conferences, ultimately aiming to advance breast cancer research and improve patient outcomes.

1. Whitworth P, et al. Annals of Surgical Oncology. 2022.
2. Tolaney SM, et al. Journal of Clinical Oncology. 2021.

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Study Findings

  • In this Real-World Evidence (RWE) prospective, propensity score matched study of 1002 patients, those with increasing \ MammaPrint Index risk (High Risk) had significantly lower risk of Distant Recurrence Free Interval (DRFI) events when treated with ET+CT (endocrine therapy+chemotherapy) compared to ET only.
  • These RWE confirm MammaPrint’s comprehensive utility, as prognostic of recurrence risk and predictive of CT benefit for patients with HR+HER2- early-stage breast cancer.
  • Consistent with findings from MINDACT, patients with MammaPrint indices within Low and UltraLow Risk ranges did not derive significant CT benefit.
  • Chemotherapy benefit is not predicted by higher tumor grade after adjusting for MammaPrint Index and clinical factors.
  • Observed CT benefit in premenopausal patients with MammaPrint Low Risk tumors may be due to ovarian function suppression.1

Study Details

  • The study is based on 1002 patients with HR+HER2- tumors from FLEX who were treated with either ET only (N=501) or ET+CT (N=501) with 5-year DRFI outcomes and propensity score matched for menopausal status, tumor stage and nodal status.
  • Kaplan Meier analysis estimated DRFI2 as a DRFI as a function of the continuous MammaPrint Index for each treatment group, with predicted 95% confidence intervals (CIs). Cox proportional hazards model was used to test for interaction between CT treatment and genomic and clinical variables. P-values of <0.05 were considered significant.

CLINICAL CHARACTERISTICS

Clinical characteristics

Differences in clinical characteristics were assessed using Student’s t-test, Chi-squared or Fisher’s Exact Test. Unknown variables were excluded.

MULTIVARIATE ANALYSIS

Hazards Ratio (HR) presented as HR (95% Confidence Interval)

WHAT IS FLEX

The FLEX study (NCT03053193) is a prospective real-world data (RWD) study focused on breast cancer, integrating full genomic profiling through MammaPrint and BluePrint with comprehensive clinical data. Its primary objective is to gather genomic and clinical information from 30,000 breast cancer patients and monitor them for over 10 years. This study is inclusive of both men and women diagnosed with stage I, II, or III breast cancer across all clinical subtypes, ensuring a representative dataset that encompasses various ethnicities, ages, genders, and health statuses. FLEX aims to facilitate research into differences and trends among breast cancer patients, particularly targeting smaller, diverse demographics that are often underrepresented in clinical trials. The study has enrolled over 20,000 patients, making it the largest, most diverse, single tumor registry of its kind. Currently data from FLEX has supported over 100 investigator initiated studies and has contributed to 6 peer-reviewed publications and over 54 abstracts at international conferences, ultimately aiming to advance breast cancer research and improve patient outcomes.

1. Whitworth P, et al. Annals of Surgical Oncology. 2022.
2. Tolaney SM, et al. Journal of Clinical Oncology. 2021.

Explore More