Objective: To evaluate the changes in age at presentation of tumor over the different generations in families at high risk for breast and ovarian cancer, in order to optimize counseling and individualizing advice concerning initiation of screening/preventive surgery.
Methods: Pedigrees from all patients tested at the Centre of Human Genetics Leuven between 3-1994 and 1-2007 were drawn. All known affected family members of tested patients were introduced in a sub-database. Type of tumor and age at presentation were collected; generation level linked. Multilevel models were used to estimate the average generation shift accounting for family-and-generation based. Secondly, the age of tumor diagnosis in the last generation was evaluated in function of the age at onset of family members of previous generations. A linear mixed model was used with the age at onset from members of the last generation as a response variable and the minimum either mean age at onset from family members of previous generations as explanatory variable.
Results: From 982 families (1796 tested individuals) pedigrees were available in 879, consisting in 3565 individuals in the pedigree sub-database. Analysis estimates that the average age of breast cancer presentation has decreased with approximately 7years for each generation. The same reduction in age is seen for ovarian cancer but in less magnitude, with a decrease of about 5years. Presence/absence of BRCA mutation did not interfere with these results. Results will be shown on poster presentation. The age at onset of BrC in the last generation can be predicted by the age at diagnosis of family members in previous generations, which confirms the results of our first approach, however, only in case age at diagnosis in family members is 50y or more, the age at onset is clearly lower than the age at onset in the previous generations. Age of tumor diagnosis in the latest generation is 40.7 when youngest case in the family was 30y, whereas it was 44.8 when youngest age at diagnosis in the family was 60y (p= 0.0001). No significant difference were seen between BRCA- and BRCA+ families. For OvC a similar trend can be noticed, however much weaker compared to BrC and given a much smaller sample, not significant (p=0.76).
Conclusion: There is some evidence for a decrease in the age of presentation of both breast and ovarian tumor. This generation effect is independent on BRCA status. Based on our analysis, we cannot however, further inferences on the cause of this decrease, and we are unable to evaluate whether the observed trend will be stable over time. However, the age at diagnosis of family members can to a certain extent predict the age at onset of later generations. This information can help in counseling high risk individuals regarding initiation of screening.
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