HR+/MP-H2 Breast Cancers Resemble Triple-Negative, Guiding New Therapies
Alejandro Rios Hoyo discussed findings on a subset of hormone receptor–positive, HER2-negative breast cancers classified as MP-H2.
Alejandro Rios Hoyo
A recent analysis of breast cancer subtypes reveals that a subset of hormone receptor (HR)-positive, HER2-negative breast cancers classified as high-2 (MP-H2) by the MammaPrint (MP) assay closely resemble triple-negative breast cancers in both molecular features and clinical behavior.1
This finding, which is based on data from the I-SPY2 neoadjuvant trial (NCT01042379), suggests that patients with HR+/MP-H2 breast cancer may benefit from similar aggressive treatment strategies typically used for triple-negative breast cancers, such as chemo-immunotherapy combinations.
In an interview with Targeted OncologyTM, Alejandro Rios Hoyo, associate research scientist at Yale School of Medicine, discussed these findings on a subset of HR-positive, HER2-negative breast cancers classified as MP-H2, as supported by principal component and gene expression analyses from the I-SPY2 trial.
Breast cancer, female anatomy: © peterschreiber.media - stock.adobe.com
Targeted Oncology: Can you provide some background regarding this research on the gene expression data from the I-SPY2 trial?
It is basically patients from the I-SPY2 neoadjuvant clinical trial. There is an important need to choose which patients will benefit from neoadjuvant treatment. As we know, most patients who achieve a pathologic complete response following neoadjuvant treatment present better survival outcomes in the long run. So, in this situation, we were focusing particularly on patients with HR-positive, HER2-negative breast cancer who have a high risk based on the MammaPrint assay, and therefore classified as high risk. And then we focused particularly on the ultra–high-risk, which is the MammaPrint 2 population.
What were the goals of this analysis?
The goal of this analysis was to assess whether the population of patients who were HR-positive, HER2-negative, and MammaPrint ultra-high risk [MP2] were more similar to triple-negative, ultra-high-risk [MP2] compared with hormone receptor-positive, HER2-negative, high-risk, or MP1. That was the goal of the analysis.
What methods were utilized in this research?
We used samples from the I-SPY2 trial. These were baseline samples, meaning prior to treatment. We used these samples and performed transcriptomic analysis. In the study, we found that, based on principal component analysis and Euclidean distance measurements, the hormone receptor-positive, HER2-negative, MP2 group was more similar to triple-negative MP2 than to HR-positive, HER2-negative, MP1 cancers.
We also confirmed this using differentially expressed genes, and we found that the two MP2 subgroups had fewer differentially expressed genes than the hormone receptor-positive, HER2-negative, MP2 and MP1 subtypes, which had more genes that were expressed differently. We also confirmed this using pathway analysis, and we found that the hormone receptor-positive, HER2-negative, MP2 subtype was enriched in different pathways such as DNA damage repair, proliferation, and cell cycle pathways.
This group of HR-positive, MP2 cancers that were more similar to triple-negative. How could this potentially impact treatment options for that group of patients?
We found that this subtype of patients had higher rates of pathologic complete response. We also found that the event-free survival was similar between the triple-negative and the HR-positive, MP2 subtypes, which basically means that the hormone receptor-positive, MP2 subtype behaves more similarly to triple-negative breast cancer, which we know is more aggressive, and the rates of survival are lower.
Therefore, we could find that, regardless of the treatment that was used, the rates of pathologic complete response were higher in this subtype. So, particularly with the use of immunotherapy, we could select the population of patients that are HR-positive that will benefit from neoadjuvant-based combinations, for example, chemotherapy and immunotherapy.
After this analysis, what unanswered questions are still remaining in this space?
Well, one of the questions is, what's the best treatment for this population? Combination-based treatments? So as I said, we found that the immunotherapy group had a benefit. However, this is just an exploratory analysis, and it's all from a phase 2 clinical trial, and now there will be a phase 3 clinical trial that will try to answer whether this ultra-selected population that's primary receptor–positive, MP-H2 derives a benefit from neoadjuvant chemo-immunotherapy-based combinations.
