Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival

Area of Science:

• Genetics
• Oncology
• Epidemiology

Background:

• A polygenic risk score (PRS) using 313 genetic variants (PRS₃₁₃) is known to associate with breast cancer risk.
• Understanding the association of PRS₃₁₃ with tumor characteristics and patient outcomes is essential for personalized medicine.

Purpose of the Study:

• To investigate the relationship between PRS₃₁₃ and clinicopathologic features of breast cancer.
• To evaluate the association of PRS₃₁₃ with overall survival (OS) and breast cancer-specific survival (BCSS).

Main Methods:

• Utilized data from the Breast Cancer Association Consortium (BCAC) and the MINDACT trial, including women of European and Asian ancestry.
• Employed logistic regression to analyze PRS₃₁₃ associations with clinicopathologic characteristics.
• Applied Cox regression to assess PRS₃₁₃ impact on OS and BCSS, adjusting for clinical factors and treatment.

Main Results:

• Increasing PRS₃₁₃ correlated with more favorable tumor characteristics, including lower grade, hormone receptor-positive status, and smaller tumor size.
• In European women, higher PRS₃₁₃ initially showed association with better OS and BCSS, but this effect diminished after adjusting for clinicopathologic factors and treatment.
• Consistent findings were observed in MINDACT and Asian women from BCAC.

Conclusions:

• PRS₃₁₃ is associated with favorable tumor characteristics but does not independently predict prognosis in primary breast cancer.
• Current findings suggest PRS₃₁₃ has no direct role in primary breast cancer clinical management at diagnosis.
• Higher PRS₃₁₃ is linked to increased breast cancer mortality risk, underscoring its importance for developing stratified screening strategies.