Research Papers:

The impact of reproductive life on breast cancer risk in women with family history or BRCA mutation

Angela Toss, Giovanni Grandi, Angelo Cagnacci, Luigi Marcheselli, Silvia Pavesi, Elisabetta De Matteis, Elisabetta Razzaboni, Chiara Tomasello, Stefano Cascinu and Laura Cortesi _

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Oncotarget. 2017; 8:9144-9154. https://doi.org/10.18632/oncotarget.13423

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Angela Toss1, Giovanni Grandi2, Angelo Cagnacci2, Luigi Marcheselli1, Silvia Pavesi2, Elisabetta De Matteis3, Elisabetta Razzaboni1, Chiara Tomasello1, Stefano Cascinu1, Laura Cortesi1

1Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy

2Department of Obstetrics Gynecology and Pediatrics, Obstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy

3Department of Oncology, Vito Fazzi Hospital, Lecce, Italy

Correspondence to:

Laura Cortesi, email: [email protected]

Keywords: breast cancer, family history, BRCA, reproductive factors, combined hormonal contraceptive

Received: September 13, 2016     Accepted: November 08, 2016     Published: November 17, 2016


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.

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