Lung cancer incidence and mortality in relationship to hormone replacement therapy use among women participating in the PLCO trial: a post hoc analysis

Objective To evaluate the impact of hormone replacement therapy (HRT) on the incidence and mortality of lung cancer among female participants in the prostate, lung, colorectal, and ovary (PLCO) trial. Methods All women participating in the PLCO trial with complete information about HRT exposure were included in the current analysis. All study population were aged 55-74 years without prior history of lung cancer at the time of study enrollment. Multivariate Cox regression analysis was used to evaluate the impact of HRT exposure on lung cancer incidence and mortality. For both end points, the model was adjusted for: age, body mass index, study arm, race, cigarette smoking and family history of lung cancer. Results A total of 77,911 female participants were included in the current analysis, including 27,663 participants who never used HRT before inclusion into the PLCO trial and 50,248 participants who used some form of HRT before inclusion into the PLCO trial. Prior exposure to HRT seems to be protective against the development of lung cancer in a multivariate analysis (hazard ratio for ever exposure versus never exposure 0.876; 95% CI 0.783-0.981; P = 0.022). Similarly, prior exposure to HRT seems also to be protective against death from lung cancer in a multivariate analysis (hazard ratio for ever exposure versus never exposure 0.814; 0.709-0.934; P = 0.003). Further multivariate Cox regression analysis showed that current HRT usage at the time of PLCO trial entry (and not former HRT usage) seemed to be protective against lung cancer development (hazard ratio for current versus never users 0.842; 0.743-0.954; P = 0.007) and lung cancer-specific mortality (hazard ratio for current versus never users 0.800; 0.686-0.932; P = 0.004). Conclusion HRT use at the time of PLCO trial entry seems to be associated with lower probability of lung cancer development and death. Further studies are needed to elucidate the biological mechanisms behind this observation.