New Biomarker Advances Personalized Treatment for ER+ Breast Cancer Patients

A groundbreaking study conducted by researchers at Baylor College of Medicine offers promising insights into tailoring therapies for estrogen receptor-positive (ER+) breast cancer, the most prevalent form of this disease. The research team identified a specific biomarker within preclinical ER+ breast cancer models that can predict a tumor's responsiveness to CDK4/6 inhibitors, a class of drugs used in combination with endocrine therapies.

This discovery centers on the tumor suppressor protein neurofibromin, encoded by the NF1 gene. Approximately 20% of ER+ breast cancers exhibit low levels of NF1, making them less responsive to conventional endocrine therapies that block estrogen's effects. However, these cancers demonstrate higher sensitivity to CDK4/6 inhibitors such as abemaciclib and ribociclib, especially in preclinical animal models derived from patient tumors.

The study's findings suggest that measuring NF1 levels could be instrumental in identifying patients who are more likely to benefit from CDK4/6 inhibitor treatments. This approach could optimize treatment strategies, potentially reducing unnecessary exposure to these drugs and minimizing adverse effects for patients unlikely to respond.

Led by Drs. Ze-Yi Zheng, Anran Chen, Matthew Ellis, and Eric Chang at the Lester and Sue Smith Breast Center, the research was motivated by clinical data indicating a correlation between reduced NF1 expression and increased CDK4/6 activity. The team developed innovative tests based on immunohistochemistry and mass spectrometry to directly assess NF1 protein abundance in patient samples.

As Dr. Chang emphasized, molecular data from patient samples can direct laboratory research towards more effective therapies. The team demonstrated that adding CDK4/6 inhibitors to estrogen blockers like fulvestrant results in durable tumor regressions in preclinical models. Further, analysis of biopsies from patients undergoing treatment with aromatase inhibitors followed by CDK4/6 inhibitor addition supports the potential clinical benefit of this targeted approach.

However, transitioning from preclinical success to clinical application requires reliable methods to measure NF1 levels in patients. The researchers are actively developing and refining such diagnostic tools to enable more personalized and effective treatment planning. Ultimately, this research move brings us closer to precisely targeting therapies based on tumor biology, improving outcomes for breast cancer patients.

The study is published in Science Translational Medicine and underscores the importance of molecular diagnostics in advancing personalized cancer treatment. Further clinical trials are necessary to validate these findings and integrate NF1 biomarker testing into standard care protocols.