Menopausal Hormone Therapy influences Lung Cancer Survival but not Lung Cancer Risk: Results from the California Teachers Study

Abstract

Abstract Purpose: Most studies have shown a protective or null effect of postmenopausal hormone therapy (HT) on lung cancer risk, whereas the recent post-hoc analysis of the Women's Health Initiative (WHI) showed that estrogen+progestin (E+P) decreased lung cancer survival. Given the substantial clinical implications, it is vital that the risk and survival associations be validated. Methods: We examined the associations between HT use and lung cancer risk and survival among 60,592 postmenopausal women enrolled in the prospective California Teachers Study cohort. Between 1995 and 2007, 727 women (184 never smokers) were diagnosed with lung cancer; 441 of these died as of December 31, 2007. Age-stratified, multivariable Cox proportional hazards regression was used to calculate hazard ratios (HR). Results: After adjusting for potential confounders, various measures of HT use were not associated with lung cancer risk. However, any HT use (vs. no use) was associated with a statistically significant increase in lung-cancer-specific survival [HR, 0.70; 95% confidence interval (CI), 0.56-0.87]. Among women who only used E, statistically significant increases in lung cancer survival were seen for recent use (HR, 0.59; 95% CI, 0.43-0.80), but not former use; use of only E+P was not associated with survival. Shorter duration of recent E-only use was associated with improved survival (0-5 years of use: HR, 0.29, 95% CI, 0.12-0.68; 5-15 years of use: HR, 0.60, 95% CI, 0.35-1.05; >15 years of use: HR, 0.58, 95% CI, 0.39-0.88) (trend P = 0.005). Similarly, women who reported recently using E-only for 0-5 years had a median survival time of 42.1 months versus women who reported 5-15 years of use (31 months), >15 years of use (19.1 months), or no HT use (15.6 months) (log-rank P = 0.009). Among former users of HT, a statistically significant 63% (95% CI, 0.16-0.87) decrease in lung-cancer-specific death was observed for E-only use <5 years prior to baseline, but not for E-only use >5 years prior to baseline or E+P-only use. Conclusions: Contrary to the recent finding that lung cancer survival is poorer among women in WHI taking E+P, our results suggest no effect of E+P. By contrast, postmenopausal E-only use, specifically recent use, is associated with increased lung cancer survival.