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

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

1 Grupo de Epidemiología Genética y Molecular, Programa de Genética del Cáncer Humano
2 Grupo de Genética Humana, Programa de Genética del Cáncer Humano
3 Servicio de Oncología Médica
4 Servicio de Genética
5 Servicio de Oncología Médica
6 Laboratorio de Oncología Molecular
7 IDIBELL - Institut d'Investigació Biomèdica de Bellvitge = Bellvitge Biomedical Research Institute
8 Breast Cancer Center, Medical Oncology Department
9 Fundación Pública Galega de Medicina Xenómica-SERGAS & Grupo de Medicina Xenómica-USC
10 Hospital Clínico Universitario de Valencia
11 Grupo de Cáncer Hereditario de la Comunidad Valenciana
12 Laboratorio de Biología Molecular del Servicio de Análisis Clínico
13 Grupo de Genética del Cáncer
14 Consorcio Hospitalario Provincial de Castellón
15 Laboratorio de Genética Molecular
16 Sección de Genética Médica, Servicio de Bioquímica Clínica
17 Unidad de Consejo Genético en Cáncer
18 Centro de Investigación del Cáncer
19 Servicio de Genética Médica
20 Centro de Investigación Biomédica En Red de Enfermedades Raras (CIBER-ER)

Environmental or lifestyle factors are likely to explain part of the heterogeneity in breast and ovarian cancer risk among and mutation carriers. We assessed parity as a risk modifier in 515 and 503 Spanish female carriers of mutations in and , 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,  = 0.06), and that associated with each live-birth was 0.87 (95%CI = 0.77–0.98,  = 0.02). The latter association was observed only in women aged 40 and above (HR = 0.81, 95%CI = 0.70–0.94,  = 0.004 vs. HR = 0.99, 95%CI = 0.83–1.18,  = 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 or mutation carriers (-trend ≥ 0.3). The power to detect associations with ovarian cancer risk was much lower, especially for mutation carriers. Nevertheless, having a live-birth was associated with protection for mutation carriers (HR = 0.41, 95%CI = 0.18–0.94,  = 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,  < 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 and . Parity appears to be protective for ovarian cancer in mutation carriers, but its role in mutation carriers remains unclear. Whether later age at first birth is also protective for ovarian cancer in mutation carriers requires further confirmation.

Mots clés: Parity; Breast cancer; Ovarian cancer

Roger L. Milne, Ana Osorio, Teresa Ramón y Cajal, Montserrat Baiget, Adriana Lasa, et al.. Parity and the risk of breast and ovarian cancer in and mutation carriers. Breast Cancer Research and Treatment, 2009, 119 (1), pp.221-232. ⟨10.1007/s10549-009-0394-1⟩. ⟨hal-00535359⟩