Breast cancer genetic risk profile is differentially associated with interval and screen-detected breast cancers
Menée à partir de l'analyse génétique d'échantillons tumoraux prélevés sur des patientes atteintes d'un cancer du sein de l'intervalle (782 cas) ou d'un cancer du sein détecté par une mammographie de dépistage (1 865 cas), ainsi qu'à l'aide d'un système de score basé sur la présence de 77 polymorphismes à simple nucléotide prédisposant au cancer du sein (77-PSN), cette étude montre que l'association entre le profil génétique, identifié par le système de score 77-PSN, et les deux types de cancer varie en fonction de la densité mammaire des patientes
Background : Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences.
Patients and methods : A 77-SNP polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen-receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term.
Results : PRS weighted by breast cancer overall estimates was found to be differentially associated with 1,865 screen-detected and 782 interval cancers in the LIBRO-1 study (age-adjusted ORperSD [95% confidence interval]=0.91 [0.83-0.99], p=0.023). The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates (ORperSD=0.90 [0.82-0.98], p=0.011). This result was corroborated by two independent studies (combined ORperSD=0.87 [0.76-1.00], p=0.058) with no evidence of heterogeneity. When enriched for “true” interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced (ORperSD=0.74 [0.62-0.89], p=0.001), with a significant interaction effect between PRS and mammographic density (pinteraction=0.017).
Conclusion : To our knowledge, this is the first report looking into the genetic differences between screen-detected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology.
Annals of Oncology , article en libre accès, 2014