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

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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.


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.


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).


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.

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Datasets of PLCO trial are available at


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The author thanks the National Cancer Institute for access to NCI’s data collected by the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The statements contained herein are solely those of the author(s) and do not represent or imply concurrence or endorsement by NCI.



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OA-R is the sole author of this manuscript.

Correspondence to Omar Abdel-Rahman.

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The author declare that there is no conflict of interest.

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All included patients in the PLCO trial signed informed consent. IRBs of all participating centers have approved the study prior to starting the study.

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Abdel-Rahman, O. Lung cancer incidence and mortality in relationship to hormone replacement therapy use among women participating in the PLCO trial: a post hoc analysis. Int J Clin Oncol (2020) doi:10.1007/s10147-020-01615-y

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  • Lung cancer
  • Women
  • HRT
  • PLCO trial
  • Incidence
  • Mortality