Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes.

Curtit E1,2, Pivot X3, Henriques J4, Paget-Bailly S4, Fumoleau P5, Rios M6, Bonnefoi H7, Bachelot T8, Soulié P9, Jouannaud C10, Bourgeois H11, Petit T12, Tennevet I13, Assouline D14, Mathieu MC15, Jacquin JP16, Lavau-Denes S17, Darut-Jouve A18, Ferrero JM19, Tarpin C20, Lévy C21, Delecroix V22, Trillet-Lenoir V23, Cojocarasu O24, Meunier J25, Pierga JY26, Kerbrat P27, Faure-Mercier C28, Blanché H29, Sahbatou M29, Boland A30, Bacq D30, Besse C30, Thomas G31, Deleuze JF29,30, Pauporté I28, Romieu G32, Cox DG33.

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Abstract

BACKGROUND:

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.

METHODS:

A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS.

RESULTS:

The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1-97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival.

CONCLUSIONS:

In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients' outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis.