Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy

Area of Science:

• Oncology
• Translational Research
• Biomarker Discovery

Background:

• Neoadjuvant systemic therapy (NAT) is standard for many cancers, but biomarker changes after treatment in patients with residual disease (RD) are not well understood.
• Hormone receptor (HR) and HER2 status are critical for treatment decisions, and their alteration post-NAT may affect patient outcomes.

Purpose of the Study:

• To investigate the prevalence of biomarker changes (HR and HER2) in patients with RD after NAT.
• To evaluate the impact of these biomarker changes on disease-free survival (DFS) and overall survival (OS).

Main Methods:

• A cohort of 303 patients treated with NAT between 2008 and 2016 with available biomarker data at diagnosis and after NAT (if RD present) was analyzed.
• Patients were categorized based on biomarker change: no change, clinically insignificant change, or clinically significant change affecting HR or HER2 status.
• Survival outcomes (DFS and OS) were compared across these groups and specific subgroups, including triple-negative (TN) and HR+/HER2- disease.

Main Results:

• 61.4% of patients had RD, and 32.8% of those experienced at least one biomarker change.
• No biomarker change was associated with significantly improved DFS (p=0.043) and OS (p=0.005) compared to significant changes.
• Clinically insignificant biomarker changes also correlated with improved OS (p=0.019).
• The HR+/HER2- to TN subgroup showed significantly worse DFS (p=0.029) and OS (p=0.008) compared to the HR+/HER2- no change group.

Conclusions:

• Biomarker status alterations are frequent in patients with RD post-NAT and have significant prognostic implications, particularly in HR+ or TN disease.
• Retesting biomarkers after NAT is crucial for accurately assessing prognosis and guiding subsequent treatment strategies.