Breast Cancer Research and Treatment

, Volume 119, Issue 1, pp 221–232

Parity and the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers

  • Roger L. Milne
  • Ana Osorio
  • Teresa Ramón y Cajal
  • Montserrat Baiget
  • Adriana Lasa
  • Eduardo Diaz-Rubio
  • Miguel de la Hoya
  • Trinidad Caldés
  • Alex Teulé
  • Conxi Lázaro
  • Ignacio Blanco
  • Judith Balmaña
  • Gessamí Sánchez-Ollé
  • Ana Vega
  • Ana Blanco
  • Isabel Chirivella
  • Eva Esteban Cardeñosa
  • Mercedes Durán
  • Eladio Velasco
  • Eduardo Martínez de Dueñas
  • María-Isabel Tejada
  • María-Dolores Miramar
  • María-Teresa Calvo
  • Carmen Guillén-Ponce
  • Raquel Salazar
  • Carlos San Román
  • Miguel Urioste
  • Javier Benítez
Epidemiology

DOI: 10.1007/s10549-009-0394-1

Cite this article as:
Milne, R.L., Osorio, A., Ramón y Cajal, T. et al. Breast Cancer Res Treat (2010) 119: 221. doi:10.1007/s10549-009-0394-1

Abstract

Environmental or lifestyle factors are likely to explain part of the heterogeneity in breast and ovarian cancer risk among BRCA1 and BRCA2 mutation carriers. We assessed parity as a risk modifier in 515 and 503 Spanish female carriers of mutations in BRCA1 and BRCA2, respectively. Hazard ratios (HR) and their corresponding 95% confidence intervals (CI) were estimated using weighted Cox proportional hazards regression, adjusted for year of birth and study centre. The results for ever being parous and number of live-births were very similar for carriers of mutations in both genes. For all mutation carriers combined, the estimated HR associated with ever having had a live-birth was 0.74 (95% confidence interval [CI] = 0.55–1.01, P = 0.06), and that associated with each live-birth was 0.87 (95%CI = 0.77–0.98, P = 0.02). The latter association was observed only in women aged 40 and above (HR = 0.81, 95%CI = 0.70–0.94, P = 0.004 vs. HR = 0.99, 95%CI = 0.83–1.18, P = 0.9 for women under age 40), and this trend was highly consistently observed for carriers of mutations in each gene. There was no evidence of an association between breast cancer risk and age at first birth for parous BRCA1 or BRCA2 mutation carriers (P-trend ≥ 0.3). The power to detect associations with ovarian cancer risk was much lower, especially for BRCA2 mutation carriers. Nevertheless, having a live-birth was associated with protection for BRCA1 mutation carriers (HR = 0.41, 95%CI = 0.18–0.94, P = 0.03), and a strong and consistent protective effect of age at first birth was observed for parous carriers of mutations in both genes (HR = 0.65, 95%CI = 0.52–0.83, P < 0.001). This is the third independent study to find that, as in the general population, parity appears to be associated with protection from breast cancer in women with mutations in BRCA1 and BRCA2. Parity appears to be protective for ovarian cancer in BRCA1 mutation carriers, but its role in BRCA2 mutation carriers remains unclear. Whether later age at first birth is also protective for ovarian cancer in mutation carriers requires further confirmation.

Keywords

Parity Breast cancer Ovarian cancer BRCA1 BRCA2 

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Roger L. Milne
    • 1
  • Ana Osorio
    • 2
  • Teresa Ramón y Cajal
    • 3
  • Montserrat Baiget
    • 4
  • Adriana Lasa
    • 4
  • Eduardo Diaz-Rubio
    • 5
  • Miguel de la Hoya
    • 6
  • Trinidad Caldés
    • 6
  • Alex Teulé
    • 7
  • Conxi Lázaro
    • 8
  • Ignacio Blanco
    • 7
  • Judith Balmaña
    • 9
  • Gessamí Sánchez-Ollé
    • 9
  • Ana Vega
    • 10
  • Ana Blanco
    • 10
  • Isabel Chirivella
    • 11
    • 12
  • Eva Esteban Cardeñosa
    • 12
    • 13
  • Mercedes Durán
    • 14
  • Eladio Velasco
    • 14
  • Eduardo Martínez de Dueñas
    • 12
    • 15
  • María-Isabel Tejada
    • 16
  • María-Dolores Miramar
    • 17
  • María-Teresa Calvo
    • 17
  • Carmen Guillén-Ponce
    • 12
    • 18
  • Raquel Salazar
    • 19
  • Carlos San Román
    • 20
  • Miguel Urioste
    • 2
    • 21
  • Javier Benítez
    • 2
    • 21
  1. 1.Grupo de Epidemiología Genética y Molecular, Programa de Genética del Cáncer HumanoCentro Nacional de Investigaciones Oncológicas (CNIO)MadridSpain
  2. 2.Grupo de Genética Humana, Programa de Genética del Cáncer HumanoCNIOMadridSpain
  3. 3.Servicio de Oncología MédicaHospital de la Santa Creu i Sant PauBarcelonaSpain
  4. 4.Servicio de GenéticaHospital de la Santa Creu i Sant PauBarcelonaSpain
  5. 5.Servicio de Oncología MédicaHospital Clínico San CarlosMadridSpain
  6. 6.Laboratorio de Oncología MolecularHospital Clínico San CarlosMadridSpain
  7. 7.Programa de Consejo Genético en Cáncer, Instituto Catalán de Oncología-IDIBELLL’HospitaletBarcelonaSpain
  8. 8.Programa de Diagnóstico Molecular de Cáncer Hereditario, Instituto Catalán de Oncología-IDIBELLL’HospitaletBarcelonaSpain
  9. 9.Breast Cancer Center, Medical Oncology DepartmentHospital Vall d’HebronBarcelonaSpain
  10. 10.Fundación Pública Galega de Medicina Xenómica-SERGAS & Grupo de Medicina Xenómica-USCCIBER-ERSantiago de Compostela, GaliciaSpain
  11. 11.Hospital Clínico Universitario de ValenciaValenciaSpain
  12. 12.Grupo de Cáncer Hereditario de la Comunidad ValencianaValenciaSpain
  13. 13.Laboratorio de Biología Molecular del Servicio de Análisis ClínicoHospital Universitario La FeValenciaSpain
  14. 14.Grupo de Genética del CáncerInstituto de Biología y Genética Molecular (UVa-CSIC)ValladolidSpain
  15. 15.Consorcio Hospitalario Provincial de CastellónCastellónSpain
  16. 16.Laboratorio de Genética MolecularHospital de CrucesBarakaldo-BizkaiaSpain
  17. 17.Sección de Genética Médica, Servicio de Bioquímica ClínicaHospital Universitario Miguel ServerZaragozaSpain
  18. 18.Unidad de Consejo Genético en CáncerHospital Universitario de ElcheElche, AlicanteSpain
  19. 19.Centro de Investigación del CáncerUniversidad de SalamancaSalamancaSpain
  20. 20.Servicio de Genética MédicaHospital Universitario Ramón y CajalMadridSpain
  21. 21.Centro de Investigación Biomédica En Red de Enfermedades Raras (CIBER-ER)MadridSpain

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