Gene Signature as a Predictor of Breast Cancer Treatment Response

A recent study coordinated by the IrsiCaixa, Catalan Institute of Oncology, and the Germans Trias i Pujol Research Institute has unveiled a promising genetic marker that could revolutionize personalized breast cancer therapy. The research focuses on hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer, for which CDK4/6 inhibitors combined with hormone therapy are currently the standard treatment. These inhibitors work by blocking proteins involved in cell division, thereby slowing tumor growth. However, not all patients respond equally: some tumors continue to progress despite treatment.

To address this variability, scientists identified a genomic signature named KIMA (Key Immune Activation). This signature consists of the expression levels of nine genes, including STAT1, FOXP3, and TIGIT. High KIMA levels are associated with poorer outcomes, characterized by quicker tumor progression and reduced overall survival, with the average time to disease progression being 11 months in high-KIMA patients compared to 36 months in those with low levels.

The study analyzed nearly 100 patients treated at ICO Badalona, finding that 57% responded well—remaining tumor-free for over two years—while 43% had early relapses. The research also revealed that tumors in non-responders exhibited abnormal immune activation that paradoxically helped cancer resist treatment. This immune environment was characterized by the high expression of the KIMA gene signature, which indicates that a hyperactive immune system in these cases may promote tumor resistance rather than defense.

Further validation in a second clinical study confirmed that non-responders had elevated KIMA levels, reinforcing its potential as a predictive biomarker. The identification of KIMA opens new avenues for tailoring treatments, possibly by combining CDK4/6 inhibitors with immunomodulatory strategies to overcome resistance.

This discovery marks a significant step toward personalizing breast cancer treatments, allowing clinicians to better predict which patients will benefit from CDK4/6 inhibitors and to develop more effective, targeted therapy regimens.

For more details, see the full study in Clinical and Translational Medicine. This research highlights the importance of understanding the tumor immune environment and its influence on treatment efficacy, paving the way for improved outcomes in breast cancer care.