Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age

• Published in: Breast cancer research and treatment Vol. 124; no. 3; pp. 643 - 651
• Main Authors: van der Kolk, Dorina M, de Bock, Geertruida H, Leegte, Beike K, Schaapveld, Michael, Mourits, Marian J. E, de Vries, Jakob, van der Hout, Annemieke H, Oosterwijk, Jan C
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01-12-2010; Springer US; Springer; Springer Nature B.V
• Subjects: Adult; Age; Age Factors; Aged; Biological and medical sciences; BRCA1; BRCA1 Protein - genetics; BRCA2; BRCA2 Protein - genetics; Breast cancer; breast neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - prevention & control; Cancer; Cancer research; Cancer therapies; Comparative analysis; Contralateral breast cancer; DNA Mutational Analysis; Family; Female; Female genital diseases; Gene mutations; Genes; Genetic aspects; Genetic Counseling; Genetic Predisposition to Disease; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Incidence; Kaplan-Meier Estimate; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Mutation; Neoplasm Recurrence, Local; Netherlands - epidemiology; Oncology; Ovarian cancer; ovarian neoplasms; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Ovarian Neoplasms - prevention & control; Pedigree; Penetrance; Phenotype; Preclinical Study; Registries; Risk Assessment; Risk Factors; Time Factors; Tumors; Young Adult; Netherlands; Breast cancer; BRCA1; BRCA2; Contralateral breast cancer; Ovarian cancer; Incidence; Human; Breast disease; Ovary cancer; Malignant tumor; Epidemiology; Female genital diseases; Mammary gland diseases; Ovarian diseases; Contralateral; BRCA2 gene; Gene penetrance; BRCA1 gene; Elderly; Age; Cancer; Tumor suppressor gene
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-010-0805-3

Accurate estimations of lifetime risks of breast and ovarian cancer are crucial for counselling women from BRCA1/2 families. We therefore determined breast and ovarian cancer penetrance in BRCA1/2 mutation families in the northern Netherlands and compared them with the incidence of cancers in the general population in this region. We identified 1188 female mutation carriers and first-degree female relatives in 185 families with a pathogenic BRCA1 or BRCA2 mutation. The occurrence of breast cancer, contralateral breast cancer and ovarian cancer was recorded. The cumulative incidence of breast cancer by age 70 was 71.4% (95% CI 67.2-82.4%) in BRCA1 and 87.5% (82.4-92.6%) in BRCA2 mutation carriers. For ovarian cancer at age 70, it was 58.9% (53.5-64.3%) in BRCA1 and 34.5% (25.0-44.0%) in BRCA2 mutation carriers. For breast cancer we saw a rise of 24.2% in the cumulative incidence in the seventh decade for BRCA2 mutation carriers versus 6.3% for BRCA1. For ovarian cancer the rise in the seventh decade was 17.3% for BRCA1 mutation carriers and 15.1% for BRCA2. The 10-year risk for contralateral breast cancer was 34.2% (29.4-39.0%) in BRCA1 families and 29.2% (22.9-35.5%) in BRCA2. We show that the incidence of breast and ovarian cancer in BRCA2 mutation carriers and of ovarian cancer in BRCA1 mutation carriers is still high after 60 years. This may justify intensive breast screening as well as oophorectomy even after age 60. The risk of contralateral breast cancer rises approximately 3% per year, which may affect preventive choices.