Adam Brufsky, MD, PhD, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, discusses results from a prospective, observational study which assessed use of MammaPrint and BluePrint genomic assays to predict response to neoadjuvant therapy in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. 

These results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

Transcript: 

I'm here to talk about our poster that we presented at ASCO on Monday June 2^nd, 2025. It has to do with MammaPrint and BluePrint and prediction of response to neoadjuvant HER2-based chemotherapy in ER-positive, HER2-positive early-stage breast cancer. This is always an issue. When someone comes in, we're trying to figure out really what their response rate is going to be — should we be giving them neoadjuvant chemotherapy first, should we not? We investigated this using MammaPrint and BluePrint. 

The idea behind MammaPrint and Blueprint is that MammaPrint is a 70 gene assay that can divide breast cancer into 4 groups: there's “ultra-low” which are people who do extremely well with no therapy or minimal hormonal therapy for over 20 years, there's “low” which are women who do not need chemotherapy but do well with endocrine therapy, and many of them for 10 years instead of 5, there's “high1” which are women who really do better with chemotherapy and potentially even with CDK4/6 inhibitors, and then there's MammaPrint “High2” which are ultra-high and those patients tend to do better, we believe, with anthracyclines, as well as potentially PARP inhibitors and really maybe even immunotherapy, there's a lot of trials testing the hypothesis. We also have Blueprint, which is one of the few commercially available tests that allows you to do intrinsic subtyping on patients. There's “luminal A” which is slow growing, estrogen receptor-driven, “luminal B” which is faster growing, estrogen receptor driven, “HER2-enriched,” which responds to anti-HER2 agents, and then finally “basal” which behaves more like triple-negative breast cancer. 

What we did with MammaPrint and Blueprint is that we have a prospective, observational study called FLEX. And what that is, is women who come in for standard of care MammaPrint and BluePrint as part of their care, sign a consent and allow us to study all 22 000 genes on the microarray– we're studying every human gene. They also allow us to follow them prospectively for up to 10 years if not longer. We have about 22 000 patients on the study now, about 5 000 or so who have 5 years of follow up, I think we have close to 1 000 if not more, who had neoadjuvant chemotherapy in addition to their hormonal therapy. 

We looked at those patients who had HER2-positive, estrogen receptor-positive early-stage breast cancer who were getting neoadjuvant HER2-based therapy and we did a MammaPrint and BluePrint on them. What we found is that generally the patients who had HER2-enriched disease, which were about probably half to two-thirds of the women in the FLEX study that got neoadjuvant HER2-based therapy had a pCR rate of about 73% to 75%, which is pretty good. If you had luminal B disease, if you were MammaPrint high with luminal B disease, your pCR rate was about 23%, so it was a little bit less.

It kind of helps us out a little bit, confirms what we knew from other studies. We had a trial, enBreast, in the past that was also a prospective registry study done by surgeons, had a smaller number of HER2-positive, ER-positive patients. In general, I think that it just demonstrates the ability of MammaPrint and BluePrint to help segment patients into those who may respond quite nicely to neoadjuvant therapy, HER2-based therapy in particular. I think that's always the question when we have someone who has triple-positive breast cancer, HR-positive and HER2-positive, whether they should receive a neoadjuvant or HER2-based chemotherapy and systemic therapy as well. 

I think it's pretty interesting. It's neat. I think what I'm really interested in, and I think we're all really interested in is, in the women who don't have a complete response, their 3-year overall survival, disease-free survival, is less. What MammaPrint allows, and BluePrint allows, us to do the FLEX trial is allows us to figure out what genes are involved and potentially associated with that, who does great despite not having a pCR, and hopefully we'll have a genetic signature for that as well but, we really have to wait for the follow up, a little bit more to get some more data on those patients. In general, I think it was a pretty interesting study and thanks for having me.

Source: 

Samiian L, Brufsky A, Uygun S, et al. Molecular insights into HR+/HER2+ early-stage breast cancer: Neoadjuvant therapy responses by MammaPrint and BluePrint genomic subtypes. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 605