Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women's Health Initiative randomized clinical trial

Abstract

CRA1500 Background: Sex differences in lung cancer outcome suggest a potential hormonal influence; however, observational studies provide mixed findings regarding menopausal hormone therapy (HT) and lung cancer. Methods: Secondary analyses of the WHI randomized, placebo-controlled trial of daily conjugated equine estrogen (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg) in 16,608 multi-ethnic postmenopausal women, aged 50–79 were conducted on lung cancer incidence and mortality. Lung cancers were confirmed by medical record review. Results: Groups were balanced for age, race/ethnicity, and prior HT. Smoking status was also comparable (never 50%, past 40%, current 10% in both groups). Cumulative risk for lung cancer was highest in current (0.51%), compared to past (0.14%) and never (0.04%) smokers. After 5.6 years on trial intervention and 2.4 years additional follow-up (median), small cell lung cancer incidence was comparable between randomization groups (total n=26), as was subsequent small cell lung cancer mortality. Although a trend for more non-small cell lung cancer (NSCLC) diagnoses in the active hormone group was not significant (p=0.12), an apparent divergence emerged after five years, with more diagnoses in the CEE+MPA group. In addition, mortality after NSCLC diagnosis was significantly higher for the CEE+MPA group (46.3% vs 27.0%, respectively, hazard ratio (HR) 1.59, 95% CI 1.03–2.46, p=0.04). As a result, CEE+MPA group women were more likely to die from NSCLC than those on placebo (p=0.02). Conclusions: Use of CEE + MPA for over 5 years increases a woman's risk for NSCLC mortality, the leading cause of cancer death in women. These data, together with recent results indicating higher breast cancer risk (Cancer Res 2009;69(2):78s), suggest cancer impact should influence risk-to-benefit consideration for combined HT use. NSCLC outcomes (annualized %) by randomization group CEE+MPA Placebo HR 95% CI P-Value N % N % NSCLC Incidence 96 0.14% 72 0.11% 1.28 0.94, 1.73 0.12 NSCLC Mortality * 67 0.10% 39 0.06% 1.61 1.09–2.39 0.02 * Analyses begin at entry randomization Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, AstraZeneca, Eli Lilly, Novartis, Wyeth Amgen, AstraZeneca, Eli Lilly, Novartis, Wyeth Amgen