Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).

Date publication

janvier 2012

Auteurs

Membres identifiés du Cancéropôle Est :
Dr LUPORSI Elisabeth

Tous les auteurs :
Lecarpentier J, Nogues C, Mouret-Fourme E, Gauthier-Villars M, Lasset C, Fricker JP, Caron O, Stoppa-Lyonnet D, Berthet P, Faivre L, Bonadona V, Buecher B, Coupier I, Gladieff L, Gesta P, Eisinger F, Frenay M, Luporsi E, Lortholary A, Colas C, Dugast C, Longy M, Pujol P, Tinat J, Lidereau R, Andrieu N

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/22762150

Résumé

INTRODUCTION: Mutations in BRCA1 and BRCA2 confer a high risk of breast cancer (BC), but the magnitude of this risk seems to vary according to the study and various factors. Although controversial, there are data to support the hypothesis of allelic risk heterogeneity. METHODS: We assessed variation in BC risk according to factors related to pregnancies by location of mutation in the homogeneous risk region of BRCA1 and BRCA2 in 990 women in the French study GENEPSO by using a weighted Cox regression model. RESULTS: Our results confirm the existence of the protective effect of an increasing number of full-term pregnancies (FTPs) toward BC among BRCA1 and BRCA2 mutation carriers (>/=3 versus 0 FTPs: hazard ratio (HR) = 0.51, 95% confidence interval (CI) = 0.33 to 0.81). Additionally, the HR shows an association between incomplete pregnancies and a higher BC risk, which reached 2.39 (95% CI = 1.28 to 4.45) among women who had at least three incomplete pregnancies when compared with women with zero incomplete pregnancies. This increased risk appeared to be restricted to incomplete pregnancies occurring before the first FTP (HR = 1.77, 95% CI = 1.19 to 2.63). We defined the TMAP score (defined as the Time of Breast Mitotic Activity during Pregnancies) to take into account simultaneously the opposite effect of full-term and interrupted pregnancies. Compared with women with a TMAP score of less than 0.35, an increasing TMAP score was associated with a statistically significant increase in the risk of BC (P trend = 0.02) which reached 1.97 (95% CI = 1.19 to 3.29) for a TMAP score >0.5 (versus TMAP /=1 versus 0 FTP: HR = 0.27, 95% CI = 0.13 to 0.55) (Pinteraction

Référence

Breast Cancer Res. 2012 Jul 3;14(4):R99