New research from the I-SPY2 neoadjuvant trial has uncovered striking similarities between a subset of hormone receptor-positive breast cancers and triple-negative breast cancer, potentially revolutionizing treatment approaches for these patients.
The analysis, led by researchers at Yale School of Medicine, focused on hormone receptor (HR)-positive, HER2-negative breast cancers classified as high-2 (MP-H2) by the MammaPrint assay. Their findings reveal that these tumors share significant molecular and clinical characteristics with triple-negative breast cancers, suggesting new therapeutic strategies may be warranted.
Molecular Similarities and Clinical Implications
Using transcriptomic analysis of baseline samples from the I-SPY2 trial, researchers found that HR+/MP-H2 breast cancers more closely resembled triple-negative MP2 tumors than their HR+/MP-H1 counterparts. Principal component analysis and Euclidean distance measurements confirmed this unexpected similarity.
"We found that this subtype of patients had higher rates of pathologic complete response," explained Alejandro Rios Hoyo, associate research scientist at Yale School of Medicine. "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."
Distinctive Molecular Pathways
The research team identified several key pathways enriched in HR+/MP-H2 breast cancers, including:
- DNA damage repair mechanisms
- Cell proliferation pathways
- Cell cycle pathways
These molecular characteristics align more closely with triple-negative breast cancer biology than traditional HR-positive disease profiles.
Treatment Implications and Future Directions
The findings suggest that patients with HR+/MP-H2 breast cancers might benefit from more aggressive treatment approaches typically reserved for triple-negative disease. Particularly promising are combination therapies incorporating both chemotherapy and immunotherapy in the neoadjuvant setting.
"Regardless of the treatment that was used, the rates of pathologic complete response were higher in this subtype," noted Rios Hoyo. "Particularly with the use of immunotherapy, we could select the population of patients that are HR-positive that will benefit from neoadjuvant-based combinations."
Next Steps in Clinical Research
While these findings are promising, they emerge from a phase 2 clinical trial and require further validation. A planned phase 3 clinical trial will specifically investigate whether HR+/MP-H2 patients derive significant benefit from neoadjuvant chemo-immunotherapy combinations.
This research represents a significant step forward in breast cancer subtype classification and treatment optimization, potentially leading to more personalized and effective therapeutic strategies for patients with HR+/MP-H2 breast cancer.
