Molecularly Guided Treatment in Hormone Receptor–Positive Breast Cancer: From Genomic Testing to Drug Development
Authors: Dr. Takahiro Kogawa
Institution: Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
Introduction
Hormone receptor-positive (HR-positive), HER2-negative breast cancer is increasingly becoming a model for molecularly guided cancer therapy. Although endocrine therapy remains the backbone of treatment, acquired resistance is associated with diverse molecular alterations, including ESR1 mutations and activation of the PI3K–AKT pathway. Understanding these evolving molecular profiles is becoming increasingly important for treatment selection and sequencing.
Methods
Advances in molecular diagnostics, including focused genomic testing, comprehensive genomic profiling, and circulating tumour DNA (ctDNA) analysis, now allow molecular information to be incorporated into routine clinical decision-making. However, the key questions are not only what to test but also when to test, which specimen to use, and how the results should influence treatment. Emerging strategies such as ctDNA-guided detection of acquired ESR1 mutations illustrate how molecular monitoring may further refine endocrine treatment.
Results
This presentation will review recent advances in molecularly guided therapy for HR-positive breast cancer, incorporating our experience with the phase II AGAIN study evaluating abemaciclib rechallenge and molecular analyses after progression, as well as early clinical development of targeted therapies such as the FGFR1–3 inhibitor tasurgratinib (E7090) and the Japanese phase I study of camizestrant. These experiences demonstrate how translational research and early-phase clinical trials can help clarify mechanisms of resistance and identify new therapeutic opportunities.
Conclusion
Another important challenge is the interval between the emergence of global clinical evidence and actual access to new drugs and diagnostic tests in individual countries. Participation in global drug development and regionally relevant early-phase studies is therefore essential to reduce this gap. At the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, genomic research, including comprehensive and whole-genome approaches, is increasingly integrated with translational research and early clinical development. This presentation will highlight how molecular testing, drug development, and clinical implementation can be connected to deliver more precise treatment for patients with breast cancer.