Gene Signature Test Predicts Response to Key Breast Cancer Treatment

DK4/6 inhibitors paired with hormone therapy have become a cornerstone treatment for advanced HR+/HER2– breast cancer, slowing tumor growth by blocking key proteins that drive cell division. However, a subset of patients sees rapid disease progression despite receiving these therapies. Now, a new study has revealed a genomic signature that can predict which tumors are unlikely to respond well to CDK4/6 inhibition, offering a path toward more personalized treatment choices.

The coordinated study by a consortium that included researchers from Germans Trias i Pujol Research Institute (IGTP, Barcelona, Spain) identified KIMA, a nine-gene immune activation signature associated with early relapse and poorer survival in HR+/HER2– breast cancer patients treated with CDK4/6 inhibitors. Their findings, published in Clinical and Translational Medicine, were based on an analysis of nearly 100 patients treated at ICO Badalona, where 57% responded well to therapy while 43% relapsed early.

Tumors from poor responders showed an abnormal, counterproductive immune activation state that strengthens tumor resistance rather than stimulating tumor clearance. Elevated expression of genes such as STAT1, FOXP3, and TIGIT formed the basis of the KIMA signature. Patients with high KIMA activity experienced tumor progression in a median of 11 months compared with 36 months for those with low KIMA levels.

A second clinical cohort confirmed the association between high KIMA and poor treatment response. The study’s results suggest that KIMA could serve as a clinical biomarker to help predict therapeutic response and guide more effective, individualized care for patients with advanced HR+/HER2– breast cancer.

"What we have seen is that, in this type of cancer, a highly activated immune system does not mean more defense, but more resistance of the tumor. This genetic signature allows us to identify these patients early on and opens the door to combining CDK4/6 inhibitors with novel immunomodulatory strategies," explained the co-senior authors of the study.

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