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

  • Epidemiology
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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.

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Acknowledgments

We thank the patients and families without whose generous participation this study would not have been possible. We also thank Alicia Barroso and Fernando Fernández who conducted the genetic testing at the Centro Nacional de Investigaciones Oncológicas; Guillermo Pita for information technology support; Marina Pollán and Fernando Artalejo from the Universidad Autónoma de Madrid; M. Carmen Alonso, Consol López and David Fisas from the Hospital de la Santa Creu i Sant Pau; Daniel Fortuny, Neus Gadea, and Orland Díez from Hospital Vall d’Hebron; Vicenta Garcés from the Hospital Clínico Universitario de Valencia, Pascual Bolufer from the Laboratorio de Biología Molecular, Hospital La Fe de Valencia; Dolores Salas and Dolores Cuevas from the Grupo de Cáncer Hereditario, Comunidad Valenciana. This work was partly supported by a grant from the Fondo de Investigación Sanitario [PI081120]. TC, MdH and ED-R were supported by the RTICC (RD06/0020/0021), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation and a grant from the Fundación de Investigación Médica Mutua Madrileña (FMMA/06). The work at the Instituto Catalán de Oncología was supported by grants ISCIII-RETIC RD06/0020/1051 and 2005SGR00018. The Fundación Pública Galega de Medicina Xenómica -SERGAS component of this work was partially supported by grants from the Ministerio de Sanidad y Consumo (PI052275) and the Xunta de Galicia (PGIDIT06BTF910101PR) to AV. AB has a fellowship from the Instituto de Salud Carlos III. The work at the Instituto de Biologia y Genetica Molecular was partly supported by the Hereditary Cancer Prevention Programme of the Regional Government of Castilla y León, and grant PI06/1102 (Fondo de Investigación Sanitaria, Instituto de Salud Carlos III). The work at the Hospital de Cruces was funded by the grant BIO07/CA/006.

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Authors and Affiliations

  1. Grupo de Epidemiología Genética y Molecular, Programa de Genética del Cáncer Humano, Centro Nacional de Investigaciones Oncológicas (CNIO), C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain

    Roger L. Milne

  2. Grupo de Genética Humana, Programa de Genética del Cáncer Humano, CNIO, Madrid, Spain

    Ana Osorio, Miguel Urioste & Javier Benítez

  3. Servicio de Oncología Médica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Teresa Ramón y Cajal

  4. Servicio de Genética, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Montserrat Baiget & Adriana Lasa

  5. Servicio de Oncología Médica, Hospital Clínico San Carlos, Madrid, Spain

    Eduardo Diaz-Rubio

  6. Laboratorio de Oncología Molecular, Hospital Clínico San Carlos, Madrid, Spain

    Miguel de la Hoya & Trinidad Caldés

  7. Programa de Consejo Genético en Cáncer, Instituto Catalán de Oncología-IDIBELL, L’Hospitalet, Barcelona, Spain

    Alex Teulé & Ignacio Blanco

  8. Programa de Diagnóstico Molecular de Cáncer Hereditario, Instituto Catalán de Oncología-IDIBELL, L’Hospitalet, Barcelona, Spain

    Conxi Lázaro

  9. Breast Cancer Center, Medical Oncology Department, Hospital Vall d’Hebron, Barcelona, Spain

    Judith Balmaña & Gessamí Sánchez-Ollé

  10. Fundación Pública Galega de Medicina Xenómica-SERGAS & Grupo de Medicina Xenómica-USC, CIBER-ER, Santiago de Compostela, Galicia, Spain

    Ana Vega & Ana Blanco

  11. Hospital Clínico Universitario de Valencia, Valencia, Spain

    Isabel Chirivella

  12. Grupo de Cáncer Hereditario de la Comunidad Valenciana, Valencia, Spain

    Isabel Chirivella, Eva Esteban Cardeñosa, Eduardo Martínez de Dueñas & Carmen Guillén-Ponce

  13. Laboratorio de Biología Molecular del Servicio de Análisis Clínico, Hospital Universitario La Fe, Valencia, Spain

    Eva Esteban Cardeñosa

  14. Grupo de Genética del Cáncer, Instituto de Biología y Genética Molecular (UVa-CSIC), Valladolid, Spain

    Mercedes Durán & Eladio Velasco

  15. Consorcio Hospitalario Provincial de Castellón, Castellón, Spain

    Eduardo Martínez de Dueñas

  16. Laboratorio de Genética Molecular, Hospital de Cruces, Barakaldo-Bizkaia, Spain

    María-Isabel Tejada

  17. Sección de Genética Médica, Servicio de Bioquímica Clínica, Hospital Universitario Miguel Server, Zaragoza, Spain

    María-Dolores Miramar & María-Teresa Calvo

  18. Unidad de Consejo Genético en Cáncer, Hospital Universitario de Elche, Elche, Alicante, Spain

    Carmen Guillén-Ponce

  19. Centro de Investigación del Cáncer, Universidad de Salamanca, Salamanca, Spain

    Raquel Salazar

  20. Servicio de Genética Médica, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Carlos San Román

  21. Centro de Investigación Biomédica En Red de Enfermedades Raras (CIBER-ER), Madrid, Spain

    Miguel Urioste & Javier Benítez

Authors
  1. Roger L. Milne
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  2. Ana Osorio
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  3. Teresa Ramón y Cajal
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  4. Montserrat Baiget
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  5. Adriana Lasa
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  6. Eduardo Diaz-Rubio
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  7. Miguel de la Hoya
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  8. Trinidad Caldés
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  9. Alex Teulé
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  10. Conxi Lázaro
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  11. Ignacio Blanco
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  12. Judith Balmaña
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  13. Gessamí Sánchez-Ollé
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  14. Ana Vega
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  15. Ana Blanco
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  16. Isabel Chirivella
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  17. Eva Esteban Cardeñosa
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  18. Mercedes Durán
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  19. Eladio Velasco
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  20. Eduardo Martínez de Dueñas
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  21. María-Isabel Tejada
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  22. María-Dolores Miramar
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  23. María-Teresa Calvo
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  24. Carmen Guillén-Ponce
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  25. Raquel Salazar
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  26. Carlos San Román
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  27. Miguel Urioste
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  28. Javier Benítez
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Correspondence to Roger L. Milne.

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Milne, R.L., Osorio, A., Ramón y Cajal, T. et al. Parity and the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 119, 221–232 (2010). https://doi.org/10.1007/s10549-009-0394-1

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  • DOI: https://doi.org/10.1007/s10549-009-0394-1

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