Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial - PubMed (original) (raw)

Randomized Controlled Trial

. 2009 Oct 10;374(9697):1243-51.

doi: 10.1016/S0140-6736(09)61526-9. Epub 2009 Sep 18.

Ann G Schwartz, Heather Wakelee, Garnet L Anderson, Marcia L Stefanick, JoAnn E Manson, Rebecca J Rodabough, Jason W Chien, Jean Wactawski-Wende, Margery Gass, Jane Morley Kotchen, Karen C Johnson, Mary Jo O'Sullivan, Judith K Ockene, Chu Chen, F Allan Hubbell; Women's Health Initiative Investigators

Collaborators, Affiliations

Randomized Controlled Trial

Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial

Rowan T Chlebowski et al. Lancet. 2009.

Abstract

Background: In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period.

Methods: The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00000611.

Findings: After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups.

Interpretation: Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer.

Funding: National Heart, Lung and Blood Institute, National Institutes of Health.

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Conflict of interest statement

Conflicts of Interest

RTC has received speaker’s fee and honorarium for advisory boards and consulting from AstraZeneca, Novartis; honorarium for advisory boards and consulting for Lilly, Amgen and Pfizer and grant support from Amgen. RTC, GLA, MLS. JEM, JW, MG, JMK, KCJ, MJO, JKO and FAH have received grant support from NIH; KCJ and RTC additionally have received grant support from the National Cancer Institute of Canada. MG has received grant support from Wyeth. AGS, HW, RJR, JWC and CC have no conflicts of interest.

Figures

Figure 1

Figure 1

Kaplan-Meier cumulative hazards for incidence from lung cancer by category, randomization group and by time in the trial. Hazard ratios (HR), 95% confidence interval (CI), and P-values are from Cox proportional hazards regression models, stratified by age and dietary modification randomization group.

Figure 2

Figure 2

Kaplan-Meier cumulative hazard for death from lung cancer by category, randomization group and time in the trial. Hazard ratios (HR), 95% confidence interval (CI), and P-values are from Cox proportional hazards regression models, stratified by age and dietary modification randomization group.

Comment in

References

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