Does comorbid disease interact with cancer? An epidemiologic analysis of mortality in a cohort of elderly breast cancer patients

Background. Although widely believed that co-occurring chronic diseases in elderly persons do not act independently in causing death, there has been little empirical research assessing prognostic interrelationships between comorbidities. Methods. Nonconcurrent prospective follow-up of 3,549 Virginia-resident elderly women diagnosed with a first breast cancer and 2,114 elderly women with no breast cancer history admitted to Virginia hospitals with principal diagnoses of genital prolapse during 1986-1988 was conducted through linkage of cancer registry and Medicare administrative records. Aggregate comorbidity was measured from Medicare claims via the Charlson comorbidity index (CCI). Mortality rates and relative risks were estimated for the breast cancer and non-breast-cancer groups stratified by the presence and level of comorbidity. Proportional hazards models were used to estimate Rothman's synergy index (S) measure of additive interaction. Results. Over full follow-up, the excess mortality rate for women with breast cancer and other comorbidity was 17% greater than expected under the null hypothesis that risks were additive and independent (S = 1.17, p =.12). Stratified analyses revealed a pattern of S estimates across cancer stage subgroups that was biologically sensible, but this pattern was not supported by strong statistical evidence. Conclusions. This study provides the first empirical estimates of statistical interaction between breast cancer and other chronic comorbidity. S index values tended to be small, but these small effects would translate into substantial numbers of deaths attributable to interaction between cancer and comorbidity. Interactions between breast cancer and comorbid disease should be explored further in large studies that can estimate these effects with increased precision.