Test May Predict Breast Cancer Recurrence Risk, Chemotherapy Benefit

Among patients with hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer, the 70-gene profiling test MammaPrint has been found to be predictive of both distant recurrence-free interval prognosis and chemotherapy benefit, researcher has shown.

Findings related to the predictive capability of the MammaPrint test were published in JNCI Cancer Spectrum.

“This [real-world data] analysis of the prospective FLEX registry demonstrates a significant chemotherapy benefit in patients with MammaPrint High Risk, HR+HER2- early [breast cancer] within a propensity score-matched cohort,” researchers noted in the study. “These data further confirm MammaPrint’s utility in identifying patients with low risk cancers who can safely forego chemotherapy. These findings … support the utility of MammaPrint as both a predictive and prognostic tool in assessing the likelihood of chemotherapy benefit in HR+HER2- early-stage [breast cancer].”

“I think tests like MammaPrint are valuable because they look at the genes that are driving the cancer and making it behave the way it does,” Dr. William Audeh told CURE in a recent interview. “This is extra, helpful information that we can't get any other way, as it's not available from looking at the cancer under a microscope. The MammaPrint test looks at 70 genes that are either overactive or underactive to predict how the cancer might behave.”

Audeh is the chief medical officer of Agendia, Inc., the company behind the MammaPrint test.

MammaPrint, researchers stated in the study, previously demonstrated utility in the guidance of chemotherapy de-escalation among patients with genomically low-risk patients as part of the MINDACT trial.

“Low-risk cancers, which include both low and ultra-low, are those that we don't think have a very high chance of coming back, at least not in the next five years or so,” Audeh told CURE. “This type of cancer doesn't appear to need chemotherapy at all, but it does need anti-estrogen therapy. High-risk cancers seem to have a higher chance of coming back earlier, which means that chemotherapy is an important initial treatment for that kind of cancer.

“Within the low-risk category, we have two subcategories: ultra-low and low. Ultra-low is unique. We've found that, at least for women who are past menopause, an ultra-low result identifies a type of breast cancer with such a good outcome that they may not even need the full five years of anti-estrogen medication, which is the standard duration of treatment. If you are ultra-low and experiencing side effects from those medications, it appears safe to stop earlier than five years.”

For the study for which findings were published in JNCI Cancer Spectrum, 1,002 patients who had been treated with endocrine therapy with or without chemotherapy were enrolled in the FLEX Registry trial, with a median follow-up of five years. MammaPrint was found to strongly predict five-year distant recurrence-free interval in patients regardless of whether they’d been treated with chemotherapy, corresponding to an average absolute chemotherapy benefit of 5.6% in patients with high 1 risk disease and 10.9% in patients with high 2 risk disease, while minimal improvement in distant recurrence-free interval with chemotherapy was observed for low (1.7%) and ultra-low (less than 1%) risk groups. Furthermore, increasing MammaPrint Index risk was associated with greater chemotherapy benefit on distant recurrence-free interval, while chemotherapy benefit was significantly associated with premenopausal status, but not age, T-stage, nodal status or grade.

The FLEX Registry trial is still recruiting patients, according to its listing on clinicaltrials.gov. With an eventual enrollment of 3,000 patients, the trial is expected to see primary completion in April 2037 and study completion in December 2037, according to the listing.

References

1. “MammaPrint predicts chemotherapy benefit in HR+HER2- early breast cancer: FLEX Registry real-world data,” JNCI Cancer Spectrum; https://academic.oup.com/jncics/article/9/5/pkaf079/8228535
2. “How Risk Status Can Affect Breast Cancer Treatment Decisions,” CURE, Aug. 26, 2025; https://www.curetoday.com/view/how-risk-status-can-affect-breast-cancer-treatment-decisions
3. “MammaPrint, BluePrint, and Full-genome Data Linked With Clinical Data to Evaluate New Gene EXpression Profiles (FLEX);” https://www.clinicaltrials.gov/study/NCT03053193

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