title: Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 mutation carriers.
authors.affiliation: Institut Curie, Paris, France. INSERM, U900, Paris, France. Mines ParisTech, Fontainebleau, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lecarpentier
authors.affiliation: Institut Curie, Hôpital René Huguenin, Saint-Cloud, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.affiliation: Institut Curie, Hôpital René Huguenin, Saint-Cloud, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mouret-Fourme
authors.affiliation: Institut Curie, Service de Génétique Oncologique, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.affiliation: Institut Curie, Service de Génétique Oncologique, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Gauthier-Villars
authors.affiliation: Institut Curie, Service de Génétique Oncologique, Paris, France. Inserm, U830, Paris, France. Université Paris-Descartes, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.affiliation: Université Claude Bernard Lyon 1, Villeurbanne, France. CNRS UMR 5558, Lyon, France. Centre Léon Bérard, Unité de Prévention et Epidémiologie Génétique, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bonadona
authors.affiliation: Centre Paul Strauss, Unité d'Oncologie, Strasbourg, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fricker
authors.affiliation: Centre François Baclesse, Unité de pathologie gynécologique, Caen, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Berthet
authors.affiliation: Institut de Cancérologie Gustave Roussy, Service d'Oncologie Génétique, Villejuif, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Caron
authors.affiliation: Hôpital Arnaud de Villeneuve, CHU Montpellier, Service de Génétique médicale et Oncogénétique, Montpellier, France. INSERM 896, CRCM Val d'Aurelle, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupier
authors.affiliation: Hôpital Arnaud de Villeneuve, CHU Montpellier, Service de Génétique médicale et Oncogénétique, Montpellier, France. INSERM 896, CRCM Val d'Aurelle, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.affiliation: Centre Georges François Leclerc, Oncogénétique, Dijon, France. Hôpital d'enfants, Service de Génétique Médicale, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: CH Georges Renon, Pôle Oncologie pour la consultation oncogénétique régionale Poitou-Charentes, Niort, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Gesta
authors.affiliation: IPC, Département d'Anticipation et de Suivi des Cancers, Marseille, France. INSERM, UMR 912, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Eisinger
authors.affiliation: Centre Antoine Lacassagne, Unité d'Oncogénétique, Nice, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Mari
authors.affiliation: Institut Claudius Regaud-IUCT-Oncopole, Service d'Oncologie Médicale, Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gladieff
authors.affiliation: Centre Catherine de Sienne, Service d'Oncologie Médicale, Nantes, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lortholary
authors.affiliation: ICL Alexis Vautrin, Unité d'Oncogénétique, Vandœuvre-lès-Nancy, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Luporsi
authors.affiliation: Hôpital Couple-Enfant, Département de Génétique, Grenoble, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Leroux
authors.affiliation: Hôpital Universitaire Dupuytren, Service d'Oncologie Médicale, Limoges, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Venat-Bouvet
authors.affiliation: Nouvel Hôpital Civil, Laboratoire de Diagnostic Génétique, Strasbourg, France.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Maugard
authors.affiliation: Groupe Hospitalier Pitié-Salpêtrière, Département de Génétique, APHP, Paris, France.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Colas
authors.affiliation: Hôpital Universitaire de Rouen, Département de Génétique, Rouen, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Tinat
authors.affiliation: Université Claude Bernard Lyon 1, Villeurbanne, France. CNRS UMR 5558, Lyon, France. Centre Léon Bérard, Unité de Prévention et Epidémiologie Génétique, Lyon, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.affiliation: Institut Curie, Paris, France. INSERM, U900, Paris, France. Mines ParisTech, Fontainebleau, France. nadine.andrieu@curie.fr.
authors.forename: Nadine
authors.initials: N
authors.lastname: Andrieu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D004967:Estrogens / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016016:Proportional Hazards Models; D017584:Reproductive History; D012307:Risk Factors; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004967:Estrogens