title: The impact of reproductive life on breast cancer risk in women with family history or BRCA mutation.
abstract: Reproductive history and exogenous hormonal exposures are acknowledged risk factors for breast cancer in the general population. In women at increased breast cancer risk for genetic predisposition or positive family history, data regarding these risk factors are limited or conflicting, and recommendations for these categories are unclear. We evaluated the characteristics of reproductive life in 2522 women at increased genetic or familial breast cancer risk attending our Family Cancer Center. Breast cancers in BRCA mutation carriers were more likely to be hormone receptor negative, diagnosed at 35 years or before and multiple during the lifetime than tumors in women at increased familial risk, while the distribution of invasive cancers and HER2 positive tumors was similar in the different risk groups. At least one full-term pregnancy (HR 0.27; 95% CI 0.12-0.58; p = 0.001), breastfeeding either less (HR 0.24; 95% CI 0.09-0.66; p = 0.005) or more (HR 0.25; 95% IC 0.08-0.82; p = 0.022) than one year and late age at menopause (HR 0.10; 95% CI 0.01-0.82; p = 0.033) showed to be protective factors in BRCA mutation carriers, while in women at increased familial risk early age at first full-term pregnancy (HR 0.62; 95% IC 0.38-0.99; p = 0.048) and late menarche (HR 0.61; 95% CI 0.42-0.85; p = 0.004) showed to be the main protective factors. Finally, for the entire population, combined hormonal contraceptives demonstrated to do not increase breast cancer risk. The results of our study suggest that women at high familial risk and mutation carries develop tumors with different clinical-pathological characteristics and, consequently, are influenced by different protective and risk factors.
authors.affiliation: Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Toss
authors.affiliation: Department of Obstetrics Gynecology and Pediatrics, Obstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grandi
authors.affiliation: Department of Obstetrics Gynecology and Pediatrics, Obstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Cagnacci
authors.affiliation: Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Marcheselli
authors.affiliation: Department of Obstetrics Gynecology and Pediatrics, Obstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pavesi
authors.affiliation: Department of Oncology, Vito Fazzi Hospital, Lecce, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: De Matteis
authors.affiliation: Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Razzaboni
authors.affiliation: Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tomasello
authors.affiliation: Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cortesi
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001942:Breast Feeding; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy; D016009:Chi-Square Distribution; D003279:Contraceptives, Oral, Sequential / Q000009:adverse effects; D005260:Female; D005298:Fertility; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D007558:Italy; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D009154:Mutation; D010298:Parity; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D016016:Proportional Hazards Models; D060728:Reproductive Health; D012307:Risk Factors; D013997:Time Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D003279:Contraceptives, Oral, Sequential
keywords: BRCA; breast cancer; combined hormonal contraceptive; family history; reproductive factors