Angela DeMichele, MD, MSCE, Analyzes Data Thus Far From I-SPY2 in HR+/HER2– Early Breast Cancer

Angela DeMichele, MD, MSCE, co-leader of the Breast Cancer Research Program, co-director of 2-PREVENT Breast Cancer Translational Center of Excellence, and Alan and Jill Miller Professor in Breast Cancer Excellence at Penn Medicine in Philadelphia, spoke with CancerNetwork^® at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting about the phase 2 I-SPY2 platform trial (NCT01042379) assessing different experimental neoadjuvant therapy regimens in patients with early breast cancer.

In an analysis performed by DeMichelle and colleagues, pathologic complete response (pCR) was analyzed by tumor subtype in 987 patients. Results showed that MammaPrint High2 and Blueprint Basal signatures were indicative of pCR rates in high-risk hormone receptor–positive, HER2-negative early breast cancer.

Transcript:

What we can do now is utilize a whole panel of new biomarkers to not just evaluate the disease [from a simplistic standpoint] of estrogen receptor, progesterone receptor, and HER2 receptor status, but now by a multitude of other important biomarkers, including MammaPrint, and gene expression profiles looking at immune signatures and DNA damage repair signatures. Taken together, this essentially enables us to profile a patient’s tumor and match the therapies that they’ll receive to the specifics of their tumor. That’s truly personalized therapy. What we presented at ASCO is a decade’s worth of work from over 1000 patients who have been treated on the I-SPY2 trial and have graciously submitted their tumors for profiling. We looked at how the tumors were matched to the therapies that worked. In our next version of the trial that will be launching later this summer, we now utilize that information for new patients coming into the trial to profile the tumors up front and direct their therapy to a personalized approach based on their tumor biology.

At the meeting, we presented our data on triple-negative, HER2-positive, and estrogen receptor–positive breast cancer and broke it down into those traditional groupings. Each of those [analyses] showed the ways in which the biomarkers now help us do a better job of identifying the patients who will respond to therapies. One great example is utilizing MammaPrint in patients with estrogen receptor-positive breast cancer. We haven’t figured out how to use immunotherapy for women with estrogen receptor–positive breast cancer, but it turns out that if you utilize the MammaPrint biomarker and the patient has what’s called the ultra-high MammaPrint score, those estrogen receptor–positive cancers respond to immunotherapy just as well as triple-negative breast cancer. That’s an enormous step forward because now we’ve identified a group of women with estrogen receptor–positive breast cancer who could benefit from immunotherapy. Those results are now being taken forward into a large phase 3 trial within the national cooperative group mechanism. It’s almost like having a living laboratory where we can identify particular signals and then take those forward to push things to standard of care.

Reference

Huppert LA, Rugo HS, Pusztai L, et al. Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial. J Clin Oncol. 2022;40(suppl 16):504. doi:10.1200/JCO.2022.40.16_suppl.504