Statistical analyses of breast cancer risks for Australian BRCA1 and BRCA2 mutation carriers

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About 10 years ago two genes, called BRCA1 and BRCA2, were discovered. The normal function of these genes is to prevent breast and other cancers from developing. All people have two copies of each gene, one inherited from their mother and one from their father. Women who have inherited a fault in one copy are at increased risk of breast and ovarian cancer. There has been considerable controversy about what their actual cancer risks are, especially about how those risks might depend on their age. We have already conducted studies on this and have developed the necessary statistical methods to address these issues by analysing data from the families in which there are faulty genes. In this study we propose to use two large Australian studies, one of families with multiple-cases of breast cancer (Kathleen Cuningham Consortium for Research on Familial Breast Cancer; kConFab) and the other of the families of women with breast cancer chosen, irrespective of their family cancer histories, through the Victorian and NSW Cancer Registries (Australian Breast Cancer Family Study; ABCFS). A large amount of work has already been conducted to identify these families and test them for faults in BRCA1 and BRCA2. There are over 350 families who carry faults, making this one of the largest studies of its type in the world. We will check the cancer histories of these families and determine which members have, or are likely to have, inherited a faulty gene. We will then estimate the breast and ovarian cancer risks accurately, and with much more precision, than has been done previously. We will also use these large datasets to develop a simple method to identify which Australian women are most likely to carry a fault in BRCA1 or BRCA2, based on their personal and family cancer histories. This study will assist genetic counsellors inform Australian women who consider mutation testing for BRCA1 and BRCA2 about their cancer risks, and help make breast cancer genetics more cost effective.