Using Biomarkers to Predict Response to Immunotherapy in Breast Cancer: I-SPY2 Trial

By: Kayci Reyer
Posted: Thursday, July 20, 2023

An evaluation of biomarkers from the I-SPY2 trial, presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 102), suggests that immune markers may predict response to immuno-oncology treatment in some types of breast cancer. The analysis found that biomarkers such as ImPrint, a 53-gene signature, and other tumor immune-signaling signatures may predict treatment response in both triple-negative and hormone receptor [HR]-positive, HER2-negative breast cancers.

“The ImPrint single-sample classifier predicts response to a variety of [immuno-oncology] regimens in both subsets and may inform prioritization of [immuno-oncology versus] other treatments and best balance likely benefit [versus] risk of serious immune-related adverse events,” according to Denise M. Wolf, PhD, of the University of California, San Francisco, and colleagues.

The evaluation included 343 patients with HER2-negative breast cancer who received treatment in one of five immuno-oncology therapy arms, plus 343 controls. Chemokine- and cytokine-heavy tumor-immune signatures demonstrated the most consistent association with pathologic complete response, regardless of therapy arm or receptor status. These markers were also associated with high spatial co-localization of PD-1–positive immune cells and PD-L1–positive tumor cells, according to multiplex immunofluorescence spatial proximity measurements. This was particularly evident among patients with triple-negative disease.

Across all therapy arms, ImPrint status was found to be linked to pathologic complete response rates, which were higher for patients harboring ImPrint markers (75% vs. 23%). Although lower than the overall therapy rates, pathologic complete response rates also remained higher for control group patients who were ImPrint-positive (34% vs. 13%).

Research-grade immune markers were more likely to predict response among patients with HR-positive disease than those with triple-negative disease. Associations between pathologic complete response and 32 continuous markers, 30 of which were immune markers, plus ESR1/PGR and proliferation signatures were determined using logistic regression.

Disclosure: Dr. Wolfe reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.

2023 ASCO Annual Meeting

---