Abstract
Relatives of breast cancer cases have an increased risk of the disease. The risk increases with increasing numbers and decreasing age of onset of affected relatives. In families with a BRCA1 or a BRCA2 mutation, individual carrier status predicts the risk of breast cancer. In relatives of cases where both BRCA1 and BRCA2 mutations are excluded, the risk remains undetermined. Standardized incidence ratios (SIRs) and cumulative cancer incidences were calculated for relatives of a population-based set of early-onset breast cancer index cases (younger than age 41 years) with a defined BRCA mutation status (n = 203). In first-degree relatives (FDRs) of mutation-negative cases, breast cancer incidences (SIR = 2.3), prostate cancer incidences (SIR = 1.7), cervix cancer incidences (SIR = 3.3) and nonmelanoma skin cancer incidences (SIR = 2.8) were increased. The risks of breast cancer, prostate cancer and nonmelanoma skin cancer were further increased in FDRs of breast cancer cases younger than 36 years of age. In high-risk individuals with at least one relative with breast cancer apart from the index case, but no BRCA mutation in the family, breast cancer incidence was increased (SIR = 5.3); again the prostate cancer incidence was elevated (SIR = 2.5). The cumulative incidence of breast cancer at ages 50 and 70 years for FDRs of index cases without a BRCA mutation was 3.6% and 12.8%, respectively. Similarly, the cumulative incidence of breast cancer for high-risk women was 6.3% and 21.1% at ages 50 and 70 years, and that for FDRs of BRCA mutation carriers was 17.2% and 27.7% at the same ages. The incidence of breast cancer is increased for FDRs of women with early-onset breast cancer irrespective of the BRCA status in the family. Risk increases with decreasing age and with increasing number of affected relatives. The incidences of prostate cancer, cervix cancer and nonmelanoma skin cancer are elevated for FDRs of early-onset breast cancer cases without a BRCA mutation, indicating a possible association between these cancers and early-onset breast cancer.
Highlights
The influence of hereditary factors over breast cancer risk in women is well established
22 families where breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) mutations were identified in index individuals (17 families with BRCA1 mutations and five families with BRCA2 mutations) and 181 families without mutations were included in the study
A general female South Swedish population is added for comparison. (b) Cumulative incidence of breast cancer for women with at least two first-degree relatives with breast cancer, of which one is an index individual diagnosed younger than age 41 years and is without an identified BRCA1/BRCA2 germline mutation
Summary
The influence of hereditary factors over breast cancer risk in women is well established. In a review and meta-analysis of previously published case–control and cohort studies, Pharoah and colleagues concluded in 1997 that a woman with a relative with breast cancer has an approximately doubled breast cancer risk compared with controls. Based data from different cohort and case–control studies of different populations have been used to create risk models that are applied clinically in oncogenetic counselling. The Claus model provides cumulative breast cancer risks for women with different numbers of relatives with breast cancer or ovarian cancer at different ages. In addition to the number of FDRs with breast cancer, the Gail model takes nonhereditary risk factors into account. Relatives of breast cancer cases have an increased risk of the disease. In families with a BRCA1 or a BRCA2 mutation, individual carrier status predicts the risk of breast cancer. In relatives of cases where both BRCA1 and BRCA2 mutations are excluded, the risk remains undetermined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
