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

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

Background: 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] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95% CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 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 (HRc¼ 0.72, 95% CI ¼ 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

Imagerie hybride TEP/IRM dans le bilan des pathologies neurodégénératives : retour d’expérience

International audienceObjectifsL’imagerie hybride TEP/IRM permet de combiner de façon précise l’information moléculaire fournie par la TEP avec une grande variété de séquences IRM. L’acquisition des deux examens en une session unique minimise les désagréments pour le patient tout en maximisant les informations collectées grâce à la fusion spatiale et temporelle des deux modalités. Dans ce travail, nous discuterons, à partir de cas cliniques, l’apport des deux modalités IRM et TEP dans le bilan des pathologies neuro-dégénératives, notamment la maladie d’Alzheimer (MA), la démence fronto-temporale (DFT), l’aphasie primaire progressive (APP), la démence à corps de Lewy (DCL), l’atrophie corticale postérieure (ACP) et le déficit cognitif léger (MCI).Matériels et méthodesCent vingt-trois patients ont été adressés dans le service entre le 2/10/15 et le 12/01/16 pour un bilan de troubles cognitifs. Les acquisitions ont été réalisées avec le TEP/IRM SIGNA (GE Healthcare) qui combine une technologie TEP temps de vol avec des photomultiplicateurs au silicium et une IRM 3T. Le protocole IRM a compris des acquisitions 3DFLAIR, 3DSWAN, 3DT1 et axiales diffusion. L’acquisition TEP-FDG (2 MBq/kg) centrée sur le cerveau a été réalisée simultanément aux séquences IRM en un pas de lit de 16 minutes (champ de vue axial de 24,4 cm). Les reconstructions étaient réalisées avec l’algorithme Vue Point FX (8 itérations, 28 sous-ensembles, fréquence de coupure 3 mm) incluant correction de résolution spatiale et le temps de vol. La correction de l’atténuation était basée sur un atlas TD.RésultatsLes images TEP et IRM sont de qualité très satisfaisante pour une durée d’examen d’environ 30 minutes. Il n’a pas été identifié d’artéfact de correction lié à l’atlas gênant l’interprétation. Dans les formes jeunes de MA, d’ACP et de DCL, la TEP-FDG montrait souvent des anomalies marquées du métabolisme alors que l’IRM était normale ou montrait une atrophie non spécifique. Dans les formes plus focales (DFT, démence sémantique), les anomalies IRM et TEP étaient généralement associées. Les lésions vasculaires (leucopathies, microsaignements, séquelles d’AVC) sont facilement détectées sur les nouvelles séquences de susceptibilité magnétique (3D SWAN) ; la TEP met en évidence une éventuelle composante dégénérative associée, voire le retentissement (désafférentation) d’une lésion sous corticale.ConclusionsLa fusion des images TEP de haute résolution spatiale avec le 3DT1 permet d’améliorer la confiance diagnostique, en faisant la part entre un effet de volume partiel en cas d’atrophie ou lésion et un véritable déficit fonctionnel. L’interprétation simultanée par le médecin nucléaire et le neuroradiologue apporte au clinicien un résultat diagnostique optimisé, en particulier dans les cas complexes

Parietal involvement in the semantic variant of primary progressive aphasia with Alzheimer's disease CSF profile

International audienceSemantic variant of primary progressive aphasia (svPPA) is typically associated with non-Alzheimer’s disease (AD) pathology. However, some anatomopathological studies have found AD lesions in those patients. We compared brain perfusion SPECT of 18 svPPA patients with cerebrospinal fluid (CSF) biomarkers indicative of non-AD pathology (svPPA-nonAD) and three svPPA patients with CSF biomarkers indicative of underlying AD (svPPA-AD). All svPPA patients had severe left temporopolar hypoperfusion. SvPPA-nonAD had additional anterior cingulate and mediofrontal hypoperfusion, whereas svPPA-AD had greater left parietal and posterior cingulate involvement. Parietal damage in svPPA constitutes a biomarker for underlying Alzheimer pathology thus refining the classification of this PPA variant

GENESIS: a French national resource to study the missing heritability of breast cancer

International audienceBackground: Less than 20 % of familial breast cancer patients who undergo genetic testing for BRCA1 and BRCA2 carry a pathogenic mutation in one of these two genes. The GENESIS (GENE SISter) study was designed to identify new breast cancer susceptibility genes in women attending cancer genetics clinics and with no BRCA1/2 mutation. Methods: The study involved the French national network of family cancer clinics. It was based on enrichment in genetic factors of the recruited population through case selection relying on familial criteria, but also on the consideration of environmental factors and endophenotypes like mammary density or tumor characteristics to assess potential genetic heterogeneity. One of the initial aims of GENESIS was to recruit affected sibpairs. Siblings were eligible when index cases and at least one affected sister were diagnosed with infiltrating mammary or ductal adenocarcinoma, with no BRCA1/2 mutation. In addition, unrelated controls and unaffected sisters were recruited. The enrolment of patients, their relatives and their controls, the collection of the clinical, epidemiological, familial and biological data were centralized by a coordinating center