Angela DeMichele, MD, MSCE, Analysis of So Far I-SPY2 Data in HR+/HER2– Early Breast Cancer

Angela DeMichele, MD, MSCE, discussed how the Phase 2 I-SPY2 trial in patients with early-stage breast cancer is informing treatment decisions for patients in difficult-to-treat situations.

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

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

Transcription:

What we can do now is use a whole host of new biomarkers to not only assess disease [from a simplistic standpoint] estrogen receptor, progesterone receptor and HER2 receptor status, but now by a host of other important biomarkers, including MammaPrint, and gene expression profiles examining immune signatures and damage repair signatures to DNA. Taken together, this essentially allows us to profile a patient’s tumor and match the therapies they will receive to the specifics of their tumor. It really is personalized therapy. What we presented at ASCO represents a decade of work from over 1000 patients who were treated in the I-SPY2 trial and graciously submitted their tumors for profiling. We looked at how tumors were adapted to therapies that worked. In our next version of the trial to be launched later this summer, we are now using this information for new patients entering the trial to profile tumors in advance and guide their treatment towards 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 these traditional groups. Each of those [analyses] showed how biomarkers now help us better identify patients who will respond to therapies. A good example is the use of 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 use the MammaPrint biomarker and the patient has what’s called the ultra-high MammaPrint score, these estrogen receptor positive cancers respond as well to immunotherapy as a triple negative breast cancer. This is a huge step forward as we have now identified a group of women with estrogen receptor positive breast cancer who could benefit from immunotherapy. These results are now the subject of a large phase 3 trial within the mechanism of the national cooperative group. It’s almost like having a living lab where we can identify particular signals and then take them forward to push things towards the standard of care.

Reference

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

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