Publication: SABCS 2025

Authors: Saya Jacob, Cynthia Wu, Annuska Glas, Christina Yau, Lamorna Brown-Swigart, Gillian Hirst, Tufia Haddad, Karthik Giridhar, Anthony Elias, Rita Mukhtar, Laura Huppert, Kathy Albain, Doug Yee, Laura van’t Veer, Laura Esserman2, Jo Chien

Title: Distinct Immune and Metabolic profiles in Latin American Breast Cancer Patients With Obesity Enrolled in FLEX

Background:

• The 70-gene MammaPrint (MP) assay is prognostic for distant recurrence and predictive of benefit from adjuvant chemotherapy (CT) in patients (pts) who have not received neoadjuvant therapy

• The MP index range is from -1 to +1 with higher index indicating lower risk of early recurrence

• Risk is categorized as MP High Risk, MP Low Risk, and MP UltraLow Risk, with only MP High Risk demonstrating benefit to chemotherapy

• There are clinical scenarios in which only tissue that has been exposed to NET is available for genomic testing, however the impact of neoadjuvant endocrine therapy on genomic testing results is unknown

Methods:

• Pts were identified through the I-SPY Low Risk Registry (LRR), an observational sub-study which enrolled pts with hormone receptor positive (HR+)/HER2-negative early breast cancer ineligible for the ISPY2 trial due to MP Low Risk or UltraLow Risk status

• Pts enrolled between 2010-2020 • Pts treated at provider discretion

• We retrospectively identified 28 patients who underwent neoadjuvant endocrine therapy and had baseline biopsies and post-therapy surgical specimens available

• We performed retrospective paired analyses of MP index, BluePrint category and ER/PR expression pre and post ET • Associations were tested using paired t-test

Conclusions:

• There was no significant difference in MammaPrint (MP) risk category or index score pre and post NET

• One patient out of 28 changed from MP Low Risk to High Risk and went on to experience distant recurrence

• There was no change in BluePrint subtype pre and post NET

• There was a greater reduction in ER expression in those who had a higher risk MP score post NET compared to those without

• MP results sent from pre- and post neoadjuvant ET specimens generally did not result in clinically actionable differences. These data suggest that the MP assay could be used for tissue exposed to NET if untreated tissue is not available

• MP as a dynamic risk marker to stratify recurrence risk following NET is being evaluated in the ongoing I-SPY2 Endocrine Optimization Pilot.