The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Correction to: Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.

After publication of the original article [1], we were notified that columns in Table 2 were erroneously displayed

Etude de radioprotection en salle d'hémodynamique lors des procédures de valvuloplasties aortiques percutanées

BESANCON-BU Médecine pharmacie (250562102) / SudocSudocFranceF

Prosthesis–Patient Mismatch in Small Aortic Annuli: Self-Expandable vs. Balloon-Expandable Transcatheter Aortic Valve Replacement

International audienceProsthesis–patient mismatch (PPM) is associated with worse outcomes following surgical aortic valve replacement (SAVR). PPM has been identified in a significant proportion of TAVR, particularly in patients with small aortic annuli. Our objective was to evaluate the hemodynamic performances of balloon-expandable (BE) (Sapiens 3TM) versus two different self-expandable (SE) (Evolut ProTM, Accurate NeoTM) TAVR devices in patients with small aortic annulus defined by a computed tomography aortic annulus area (AAA) between 330 and 440 mm2. We enrolled 131 consecutive patients corresponding to 76 Sapiens 3 23 mm (58.0%), 26 Evolut Pro (19.9%) and 29 Accurate Neo (22.1%). Mean age was 82.5 ± 7.06 years, 22.9% of patients were male and mean Euroscore was 4.0%. Mean AAA was 374 ± 27 mm2 for Sapiens 3, 383 ± 29 mm2 for Corevalve Evolut Pro and 389 ± 25 mm2 for Accurate Neo. BE devices were associated with significantly higher rates of PPM (39.5%) as compared to SE devices (15.4% for Corevalve Evolut Pro and 6.9% for Accurate Neo) (p < 0.0001). Paravalvular leaks ≥ 2/4 were more often observed in SE devices (15.4% for Corevalve Evolut Pro and 17.2% for Accurate Neo) than in BE devices (2.6%) (p = 0.007). In conclusion, SE TAVR devices did achieve better hemodynamic results despite higher rates of paravalvular leaks. Therefore, SE TAVI devices could be considered as first choice in small aortic anatomy

Genetic structure and admixture of the Seychelles' population.

International audienc

Estimation du risque de cancer du sein et de l'ovaire dans une cohorte prospective de femmes porteuses d'une mutation sur les gènes BRCA : étude nationale GENEPSO

AbstractNational audienc

The level of evidence for the use of biomarkers in the early detection of prostate cancer

International audienceTo systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio

Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1/2 carrier cohort (GENEPSO).

International audienceABSTRACT: 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 homogeneous risk region of BRCA1 and BRCA2 in 990 women of the French study GENEPSO by using a weighted Cox regression model. RESULTS: Our results confirm the existence of a protective effect of an increasing number of full-term pregnancies (FTPs) toward BC among BRCA1 and BRCA2 mutation carriers ([greater than or equal to]3 vs. 0 FTPs: HR=0.51, 95% CI=0.33-0.81). Additionally, hazard ratio (HR) show an association between incomplete pregnancies and a higher BC risk, which reached 2.39 (95% CI=1.28-4.45) 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=1.19-2.63). 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=1.19-3.29) for a TMAP score > 0.5 (vs. TMAP less than or equal to 0.35). All these results appeared to be similar in BRCA1 and BRCA2. Nevertheless, our results suggest a variation in BC risk associated with parity according to the location of the mutation in BRCA1. Indeed, parity seems to be associated with a significantly decreased risk of BC only among women with a mutation in the central region of BRCA1 (low-risk region) (greater than or equal to 1 vs. 0 FTP: HR=0.27, 95% CI=0.13-0.55) (pinteraction <10-3). CONCLUSION: Our findings show that, taking into account environmental and lifestyle modifiers, mutation position might be important for the clinical management of BRCA1 and BRCA2 mutation carriers and could also be helpful in understanding how BRCA1 and BRCA2 genes are involved in BC

Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers

International audienceBACKGROUND:Mutations in BRCA1/2 confer a high risk of breast cancer, but literature values of this risk vary. A genotype-phenotype correlation has been found in both genes, and the effect of reproductive factors differs according to mutation location. Therefore, we hypothesize that such a variation may exist for other factors related to estrogen exposure.METHODS:We used a weighted Cox regression model to assess variation in breast cancer risk with these factors using location of mutation in homogeneous breast cancer risk region of BRCA1/2 in the GENEPSO study.RESULTS:We found that late age at menarche reduced breast cancer risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 65% and 73%, respectively). Among premenopausal women, overweight was associated with a 45% decrease in risk whereas underweight was associated with an increased risk (HR, 2.40). A natural menopause, mainly after age 50, was associated with a high breast cancer risk (HR, 2.46), and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause.CONCLUSIONS:As observed in the general population, a late menarche, a long or a short menstrual cycle, over- or underweight, and being postmenopausal were associated with breast cancer risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the "high-risk" zones.IMPACT:Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 mutation carriers

Time to prophylactic surgery in BRCA1/2 carriers depends on psychological and other characteristics

International audienc