Mechanisms of association between physical functioning and breast cancer mortality: evidence from the Women's Healthy Eating and Living Study.
PURPOSE
Low physical functioning among breast cancer survivors appears to reduce survival, although the mechanisms underlying these associations are not clear. We examined inflammation as a possible biological mediator of association between low physical functioning and mortality after breast cancer.


METHODS
Analysis included 2,892 participants from the Women's Healthy Eating and Living Study. All measures were collected at study baseline. Physical function was assessed by the Short Form 36 (SF-36) Health Survey Physical Function subscale. Low physical function was defined as the bottom tertile of the subscale score. Inflammation was measured as serum concentration of C-reactive protein (CRP). Cox proportional hazards modeled the associations of low physical function and the putative mediator (i.e., CRP) with all-cause and breast cancer-specific mortality.


RESULTS
There were 293 deaths during study follow up, with 243 due to breast cancer. Low physical functioning was associated with a 50 % higher risk of all-cause mortality (HR, 1.49; 95 % CI, 1.2-1.9) and a 40 % higher risk of breast cancer-specific mortality (HR, 1.39; 95 % CI, 1.1-1.8), after adjustment for covariates. The addition of CRP did not markedly change the all-cause mortality hazard ratio attributed to low physical functioning. However, the addition of CRP modestly attenuated the breast cancer-specific mortality hazard ratio such that it was no longer statistically significant.


CONCLUSIONS
Interventions to improve physical functioning may prevent early morbidity and mortality among breast cancer survivors.


IMPLICATIONS FOR CANCER SURVIVORS
Functional status measure may be a valuable indicator of long-term health outcomes among breast cancer survivors.