From Static to Dynamic: Adaptive Molecular Subtyping in Treated Breast Cancers-Evidence from Single-Center...

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Traditional breast cancer (BC) management uses static biomarkers at diagnosis.
• These biomarkers may not capture therapy-induced molecular evolution.
• Dynamic molecular profiling can offer deeper insights into tumor behavior.

Purpose of the Study:

• To evaluate if longitudinal molecular profiling before and after treatment better characterizes tumor dynamics.
• To identify clinically actionable insights into treatment response, resistance, and prognosis.
• To assess molecular plasticity under therapeutic pressure.

Main Methods:

• Analysis of 32 invasive breast carcinoma patients using histopathology, IHC, NGS, and ctDNA.
• Paired tumor tissue and plasma samples collected pre- and post-treatment.
• Assessment of changes in biomarker expression, molecular subtype, and genomic alterations.

Main Results:

• Substantial molecular discordance observed post-treatment, including PR loss (33.3%) and HER2 changes (33.3%).
• Plasma ctDNA analysis identified additional clinically relevant alterations (e.g., FGFR1 amplification, BRCA1/2 variants).
• Longitudinal assessment revealed actionable changes missed by static subtyping.

Conclusions:

• Breast cancer molecular profiles are dynamic and altered by therapy.
• Longitudinal molecular assessment provides clinically actionable insights.
• Adaptive molecular subtyping holds potential for improved treatment stratification and resistance monitoring.