Search

Background: A previous Australian population-based breast cancer case-control study found indirect evidence that control participation, although high, was not random. We hypothesized that unaffected sisters may provide a more appropriate comparison group than unrelated population controls.Methods: Three population-based case-control-family studies of breast cancer in women of white European origin were carried out by the Australian, Ontario and Northern California sites of the Breast Cancer Family Registry. We compared risk factors between 3643 cases, 2444 of their unaffected sisters and 2877 population controls and conducted separate case-control analyses based on population and sister controls using unconditional multivariable logistic regression.Results: Compared with sister controls, population controls were more highly educated, had an earlier age at menarche, fewer births, their first birth at a later age and their last birth more recently. The established breast cancer associations detected using sister controls, but not detected using population controls, were decreasing risk with each of later age at menarche, more births, younger age at first birth and greater time since last birth.Conclusions: Since participation of population controls might be unintentionally related to some risk factors, we hypothesize that sister controls could provide more valid relative risk estimates and be recruited at lower cost. Given declining study participation by population controls, this contention is highly relevant to epidemiologic research. [ABSTRACT FROM AUTHOR]

Although having a family history of breast cancer is a well established breast cancer risk factor, it is not known whether it influences mortality after breast cancer diagnosis. We studied 4,153 women with first primary incident invasive breast cancer diagnosed between 1991 and 2000, and enrolled in the Breast Cancer Family Registry through population-based sampling in Northern California, USA; Ontario, Canada; and Melbourne and Sydney, Australia. Cases were oversampled for younger age at diagnosis and/or family history of breast cancer. Carriers of germline mutations in BRCA1 or BRCA2 were excluded. Cases and their relatives completed structured questionnaires assessing breast cancer risk factors and family history of cancer. Cases were followed for a median of 6.5 years, during which 725 deaths occurred. Cox proportional hazards regression was used to evaluate associations between family history of breast cancer at the time of diagnosis and risk of all-cause mortality after breast cancer diagnosis, adjusting for established prognostic factors. The hazard ratios for all-cause mortality were 0.98 (95% confidence interval [CI] = 0.84-1.15) for having at least one first- or second-degree relative with breast cancer, and 0.85 (95% CI = 0.70-1.02) for having at least one first-degree relative with breast cancer, compared with having no such family history. Estimates did not vary appreciably when stratified by case or tumor characteristics. In conclusion, family history of breast cancer is not associated with all-cause mortality after breast cancer diagnosis for women without a known germline mutation in BRCA1 or BRCA2. Therefore, clinical management should not depend on family history of breast cancer.