Dr O’Shaughnessy on the Utility of the MammaPrint Assay in HR+ Breast Cancer

“In the FLEX trial, the higher the MammaPrint index, the more the benefit from chemotherapy...and the lower the MammaPrint index, [the lower the] benefit from chemotherapy."

Joyce O’Shaughnessy, MD, co-chair of Breast Cancer Research and chair of Breast Cancer Prevention Research at Baylor Charles A. Sammons Cancer Center, discussed the role of the MammaPrint assay in predicting chemotherapy benefit in patients with hormone receptor (HR)–positive, HER2-negative breast cancer.

In the context of early-stage, HR-positive, HER2-negative breast cancer, determining which patients truly benefit from adjuvant or neoadjuvant anthracycline-based chemotherapy remains a central clinical question, O’Shaughnessy began. The initial consideration is whether chemotherapy is required at all, given that all patients will receive endocrine therapy, and those with sufficiently high risk are also candidates for CDK4/6 inhibitors, she noted. Thus, the key clinical challenge lies in identifying which subsets of patients derive meaningful benefit from chemotherapy, she said.

Evidence demonstrates that patients with higher 21-gene recurrence scores gain significant benefit from either adjuvant or neoadjuvant chemotherapy, whereas those with low recurrence scores do not experience such benefit, O’Shaughnessy explained. Similarly, the MammaPrint 70-gene signature has been established as a prognostic tool based on results from the phase 3 MINDACT trial (NCT00433589), she contextualized. However, until recently, this signature lacked robust predictive evidence indicating whether high- or low-risk scores specifically correlate with chemotherapy benefit, she noted.

At the 2024 San Antonio Breast Cancer Symposium, results from the large, observational FLEX registry trial (NCT03053193) provided important new insights, O’Shaughnessy reported. Findings demonstrated that the degree of benefit from chemotherapy correlated directly with the MammaPrint index, she stated. Specifically, patients with higher indices derived greater benefit from chemotherapy, whereas those with lower indices did not, she continued. Importantly, the data revealed that the MammaPrint index functions as a continuous variable, reinforcing its utility in refining treatment decisions, she highlighted. This represents the first prospective predictive dataset supporting the MammaPrint assay in identifying chemotherapy benefit beyond its established prognostic role, according to O’Shaughnessy.

It is important to note, however, that FLEX was not a randomized trial, O’Shaughnessy cautioned. It was instead a large prospective real-world evidence registry in which all patients underwent MammaPrint and BluePrint testing on their tumor tissue. Although this design strengthened the dataset by including broad, real-world representation, the absence of randomization remains a limitation of this research, she concluded.