Genome Wide Association Studies (GWAS) have to date identified 94 genetic variants (Single Nucleotide Polymorphisms – SNPs) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer.
A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case-cohort. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS study. A two-staged genotyping strategy was carried out.
The median 94-SNP risk score in 8703 breast cancer patients with early breast cancer was 77.5 (ranges: 58.1 – 97.6). The risk score was not associated with usual prognostic and predictive factors (age, TNM status, Scarff-Bloom-Richardson grade, inflammatory feature, estrogen receptor status, progesterone receptor status, HER2 status) and did not correlate with breast cancer subtypes. 94-SNP risk score did not predict outcomes represented by overall survival and disease free survival.
In a prospective cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes or patient's outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutive genetic factors, variants associated with breast cancer subtypes and prognosis should be different from variants involved in the risk of developing a breast cancer.
Clinical trial identification
SIGNAL / PHARE (NCT00381901 – RECF1098).
Legal entity responsible for the study
Xavier Pivot - Institut National du Cancer - France
X. Pivot: XP received honorarium from Roche, Eisai. All other authors have declared no conflicts of interest.