Advances in Precision Therapy for HR+/HER2- Breast Cancer: Key Findings from Recent Study

Recent research conducted at Roswell Park Comprehensive Cancer Center has provided new insights into the treatment of hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer. This type of breast cancer is the most common subtype, representing 68% of cases, yet it often has a poor prognosis once it metastasizes, with only 32% of patients surviving beyond five years.

The ongoing observational clinical trial (NCT04526587) aims to understand why some patients respond better to standard targeted therapies involving CDK4/6 inhibitors—drugs that halt cancer cell division—compared to others. The study, published in npj Breast Cancer, investigates the factors influencing progression-free survival (PFS), which is the period during which the disease remains stable post-treatment.

A team led by Dr. Agnieszka Witkiewicz analyzed tumor immune profiles and cell cycle markers before treatment, focusing on their association with treatment outcomes. Notably, they discovered that high levels of cyclin A and E—proteins regulating cell division—were linked to shorter PFS and correlated with the presence of macrophages, immune cells that can support tumor growth. Conversely, in patients with longer PFS, immune activation signatures emerged during therapy, alongside a reduction in cell cycle activity.

The study highlights the potential of using tumor immune and cell cycle markers to predict responses to CDK4/6 inhibitors, paving the way for more personalized treatment approaches. These findings suggest that combining immune-targeted therapies with existing treatments might improve the durability of responses and outcomes for patients with metastatic HR+/HER2- breast cancer.