Integrating Molecular Phenotyping into Treatment Algorithms for Advanced Oestrogen Receptor-Positive Breast Cancer

Area of Science:

• Oncology
• Genomics
• Precision Medicine

Background:

• Breast cancer is a leading cause of cancer mortality globally, with ER-positive disease being the most common subtype.
• Endocrine and targeted therapies improve survival, but treatment resistance is a significant challenge.
• Molecular profiling is crucial for understanding resistance mechanisms and guiding personalized treatment strategies.

Purpose of the Study:

• To review the molecular landscape of ER-positive breast cancer and its implications for treatment resistance.
• To integrate molecular phenotyping with clinical treatment algorithms for advanced ER-positive breast cancer.
• To provide a practical framework for translating genomic insights into patient care.

Main Methods:

• Review of current literature on genomic alterations in ER-positive breast cancer.
• Integration of molecular profiling data with clinical treatment guidelines.
• Discussion of next-generation sequencing and ctDNA technologies for dynamic tumor assessment.

Main Results:

• Key genomic alterations driving resistance and targeted therapies like oral selective ER degraders (SERDs) and PI3K/AKT/mTOR inhibitors are identified.
• Emerging targets such as HER2 mutations and the role of ctDNA monitoring in detecting resistance are discussed.
• Molecular profiling is recommended for routine clinical decision-making to personalize therapy.

Conclusions:

• Personalized therapy for ER-positive breast cancer requires integrating molecular profiling into clinical practice.
• Advances in sequencing and ctDNA analysis enable dynamic assessment of tumor heterogeneity and clonal evolution.
• Addressing challenges like cost and accessibility is vital for equitable implementation of precision oncology.