A family history of breast cancer is a well established risk factor for breast cancer [1
]. Mutations in known breast cancer susceptibility genes account for only about one-quarter of this familial association [4
], so the excess risk still exists for women who do not carry a germline mutation in BRCA1
. It is unclear, however, whether all-cause mortality after breast cancer diagnosis differs between women who do and do not have a family history of breast cancer. A review of studies published between 1976 and 1999 found no consistent evidence of a mortality difference between cases with and without a family history [5
], and subsequent studies have generally found no difference with respect to all-cause mortality [6
] or other outcome measures [9
], although some reported a better [22
] or worse [23
] prognosis for cases with a family history of breast cancer. Differences in all-cause mortality between breast cancer cases with and without a family history, should they exist, might be due to differences in biology and, therefore, might give insights into breast cancer etiology, secondary prevention, treatment, and counseling.
Depending on definition, 10% or more of breast cancer cases have a family history of the disease [2
]. Having an affected first-degree relative increases risk by an average of about two-fold [1
]; about 15-20% of this excess risk is explained by germline mutations in BRCA1
]. Other, lower-penetrance susceptibility genes, as well as shared environmental factors, appear to be responsible for the remaining familial risk [27
]. Most previous studies have defined “familial breast cancer” in one of three ways: a self-reported family history of the disease, with variable inclusion of first-, second-, or third-degree relatives; BRCA1
linkage within families; or germline BRCA1
mutation carriage in cases [5
]. These definitions cover very different scenarios. In this paper, we use the term “familial” to refer to cases with a family history of the disease, and the term “non-BRCA1/BRCA2
-associated breast cancer” to refer to cases without a known germline mutation in BRCA1
Mortality differences between non-BRCA1/BRCA2
-associated breast cancer cases with and without a family history of breast cancer have not been widely investigated. One Finnish study [6
] and one Dutch study [13
] found no differences in overall survival for cases with familial non-BRCA1/BRCA2
-associated, and non-familial breast cancer.
However, neither of these studies was population-based, and both lacked detailed interview data from individual cases, limiting their ability to consider survival associations with other patient characteristics. Furthermore, few prior studies have examined whether any possible association of family history with survival varies by tumor histologic type or hormone receptor status.
It was recently reported by the population-based Ontario Breast Cancer Family Registry (CFR) that all-cause mortality after breast cancer diagnosis did not vary between cases with and without a first-degree family history of breast or ovarian cancer [15
]. Here, we expand the sample size and scope of this prior study by including cases from two additional population-based samples from the Northern California and Australian Breast CFRs. If family history were to predict breast cancer survival, then it might influence clinical practice because it can be ascertained prior to treatment. Therefore, using a large, pooled, population-based series of breast cancer cases, we set out to determine whether all-cause mortality in cases with non-BRCA1/BRCA2
-associated breast cancer varies by family history of breast cancer.