Advertisement

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

  • 39 Accesses

Abstract

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.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2

Availability of data and material

Datasets of PLCO trial are available at https://biometry.nci.nih.gov/cdas/plco/

References

  1. 1.

    Brood-van Zanten MM, Barentsen R, van der Mooren MJ (2002) Hormone replacement therapy and surveillance considerations. Maturitas. 43(Suppl 1):S57–67

  2. 2.

    Al-Azzawi F, Wahab M (2002) Estrogen and colon cancer: current issues. Climacteric. 5(1):3–14

  3. 3.

    Investigators WGftWsHI (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal womenprincipal results from the women's health initiative randomized controlled trial. JAMA 288(3):321–333

  4. 4.

    Bae J-M, Kim EH (2015) Hormonal replacement therapy and the risk of lung cancer in women: an adaptive meta-analysis of cohort studies. J Prev Med Public Health 48(6):280–286

  5. 5.

    Brinton LA, Gierach GL, Andaya A et al (2011) Reproductive and hormonal factors and lung cancer risk in the NIH-AARP diet and health study cohort. Cancer Epidemiol Biomarkers Prev. 20(5):900–911

  6. 6.

    Oken MM, Hocking WG, Kvale PA et al (2011) Screening by chest radiograph and lung cancer mortality: the prostate, lung, colorectal, and ovarian (PLCO) randomized trial. JAMA 306(17):1865–1873

  7. 7.

    Abdel-Rahman O (2018) Changing epidemiology of elderly small cell lung cancer patients over the last 40 years; a SEER database analysis. Clin Respir J. 12(3):1093–1099

  8. 8.

    Abdel-Rahman O (2019) Impact of current versus former smoking status on the outcomes of non-metastatic non-small cell lung cancer treated with upfront surgery; findings from the National Lung Screening Trial. Expert Rev Respir Med. 13(6):585–591

  9. 9.

    Schabath MB, Wu X, Vassilopoulou-Sellin R et al (2004) Hormone replacement therapy and lung cancer risk. A case-control analysis. Clin Cancer Res 10(1):113–123

  10. 10.

    Olsson H, Bladstrom A, Ingvar C (2003) Are smoking-associated cancers prevented or postponed in women using hormone replacement therapy? Obstet Gynecol. 102(3):565–570

  11. 11.

    Schwartz AG, Ray RM, Cote ML et al (2015) Hormone use, reproductive history, and risk of lung cancer: the Women's Health Initiative Studies. J Thorac Oncol. 10(7):1004–1013

  12. 12.

    Ettinger B, Friedman GD, Bush T et al (1996) Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstet Gynecol. 87(1):6–12

  13. 13.

    Li W, Lin X, Wang R et al (2017) Hormone therapy and lung cancer mortality in women: systematic review and meta-analysis. Steroids 118:47–54

  14. 14.

    Weiss JM, Lacey JV Jr, Shu XO et al (2008) Menstrual and reproductive factors in association with lung cancer in female lifetime nonsmokers. Am J Epidemiol. 168(11):1319–1325

  15. 15.

    Seow A, Koh WP, Wang R et al (2009) Reproductive variables, soy intake, and lung cancer risk among nonsmoking women in the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev. 18(3):821–827

  16. 16.

    Shimada T, Hayes CL, Yamazaki H et al (1996) Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1. Cancer Res. 56(13):2979–2984

  17. 17.

    Abdel-Rahman O (2019) Pre-diagnostic body mass index trajectory in relationship to lung cancer incidence and mortality; findings from the PLCO Trial. Expert Rev Respir Med 13:1029–1035

  18. 18.

    Collins JA, Blake JM, Crosignani PG (2005) Breast cancer risk with postmenopausal hormonal treatment. Hum Reprod Update. 11(6):545–560

  19. 19.

    Mikkola TS (2019) Cardiovascular mortality risk and HRT. In: Brinton RD, Genazzani AR, Simoncini T, Stevenson JC (eds) Sex steroids' effects on brain, heart and vessels: volume 6: Frontiers in Gynecological Endocrinology. Springer International Publishing, Cham, pp 271–274

  20. 20.

    Salpeter SR, Walsh JME, Greyber E et al (2004) Mortality associated with hormone replacement therapy in younger and older women: a meta-analysis. J Gen Intern Med. 19(7):791–804

Download references

Acknowledgements

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.

Funding

None.

Author information

OA-R is the sole author of this manuscript.

Correspondence to Omar Abdel-Rahman.

Ethics declarations

Conflict of interest

The author declare that there is no conflict of interest.

Ethics approval and consent to participate

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

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Keywords

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