Lung Cancer In Postmenopausal Women Research Articles

The association between hormone therapy and the risk of lung cancer in postmenopausal women: a 16-year nationwide population-based study.

Although an association between hormone therapy (HT) and the risk of developing lung cancer has been reported, the results on the topic are inconsistent. Our study objective was to investigate whether postmenopausal women who undergo HT exhibit a risk of developing lung cancer. In this matched cohort study, we obtained the data of 38,104 postmenopausal women older than 45 years who were treated using HT between 2000 and 2015 from Taiwan's National Health Insurance Research Database, and 152,416 matched participants who were not treated using HT were enrolled as controls at a 1:4 ratio. We used a Cox proportional hazards regression model to identify the risk of developing lung cancer during 16 years of follow-up, and the results indicate no significant difference in the proportion of postmenopausal women treated using HT ( P = 0.129) who developed lung cancer and that of those not treated using HT (0.866% [330 of 38,104] vs 0.950% [1,449 of 152,416]). After adjustment for age and other variables, the adjusted hazard ratio was 0.886 (95% CI, 0.666-1.305, P = 0.433), indicating no association between HT and lung cancer development in postmenopausal women. In a subgroup analysis, the risk of lung cancer was significantly lower in the women who were treated using HT when the HT cumulative dosage was ≥401 mg or when the therapy duration was ≥5 years compared with in those not treated using HT; the adjusted hazard ratios were 0.633 (95% CI, 0.475-0.930; P < 0.001) and 0.532 (95% CI, 0.330-0.934; P < 0.001), respectively, after adjustment. Our results indicate that HT is not associated with the risk of lung cancer development in postmenopausal women; furthermore, a higher cumulative dosage and the long-term effects of HT reduce the risk of developing lung cancer.

Female reproductive factors and the risk of lung cancer in postmenopausal women: a nationwide cohort study

BackgroundReproductive factors and hormone use in postmenopausal women have been hypothesised to affect the risk of developing lung cancer, but the epidemiological evidence is inconsistent.MethodsUsing the Korean National Health Insurance System database, we identified 4,775,398 postmenopausal women older than 40 years who had undergone both cardiovascular health- and cancer screening between 1 January 2009 and 31 December 2014. Information about reproductive factors was obtained from a self-administered questionnaire. The risk of lung cancer was estimated using Cox proportional hazard regression models.ResultsDuring a median follow-up of 4.4 years, 16,556 women (15,223 non-smokers) were diagnosed with lung cancer. The risk of lung cancer was not significantly influenced by early menarche age (adjusted hazard ratio [aHR] 1.03 for menarche ≥18 vs. ≤14; 95% confidence interval [CI], 0.98–1.09) or late age at menopause (aHR 1.02 for menopause ≥55 vs. <40; 95% CI, 0.91–1.14). Furthermore, the number of children, duration of breastfeeding and use of hormone replacement therapy were not associated with the risk of lung cancer.ConclusionsNo statistically significant association was found between reproductive factors and the risk of lung cancer in postmenopausal Korean women.

Abstract 835: COPD and risk of lung cancer in post-menopausal women: findings from the Women's Health Initiative

Abstract Background: Lung cancer and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality in the United States. Cigarette smoking is associated with both lung cancer and COPD, but whether COPD independently predicts lung cancer risk is debated. To examine this question in a large, prospective study, we constructed risk models using data from the observational study arm of the Women's Health Initiative. Methods: Initial analyses included 89,384 women (n = 1,479 lung cancers) with complete baseline information on cigarette smoking and COPD status. We created a second, time-varying model to account for incident smoking that occurred during the eight year follow up period, in addition to the number of pack years reported at baseline. Estimates from Cox proportional hazard models were used to assess the association between COPD and lung cancer. The baseline hazard was stratified by age at study entry in all models. COPD status was self-reported, and diagnoses within one year of lung cancer diagnoses were not included. Reported lung cancers were adjudicated via medical record. Results: There was an interaction between number of pack years (continuous) of smoking at baseline and COPD status (p&amp;lt;0.001). Never smokers with COPD were 2.7 times more likely to develop lung cancer compared to never smokers without COPD, after adjusting for race, education, income and body mass index (HR = 2.70, 95% CI: 2.12, 3.45). Similar risk of lung cancer associated with COPD was seen among smokers with 20 pack years of smoking (HR = 2.37, 95% CI: 1.96, 2.87) and at 40 pack years of smoking (HR = 2.08, 95% CI: 1.77, 2.45) after adjustment. From the time-varying models, women with COPD had approximately 2 times the risk of developing lung cancer compared to those who did not, after adjusting for smoking, race, education, income and body mass index (HR = 1.90, 95% CI: 1.54, 2.34). COPD was associated with all subtypes of lung cancer after adjustment for smoking, with hazard ratios ranging from 1.59-2.15 for different histological subtypes of non-small cell lung cancers. Smokers with COPD were 4.6 times more likely to develop small cell lung cancers compared to those without COPD (HR = 4.68, 95% CI: 2.67, 8.20). Conclusion: These data suggest that COPD is an independent risk factor for the development of lung cancer, and should be considered when constructing risk models. Citation Format: Michele L. Cote, Amy Lehman, Rowen Chlebowski, Brittany Haynes, Gloria Ho, Manali Patel, Lori Sakoda, Michael Simon, Heather Wakelee, Ann Schwartz. COPD and risk of lung cancer in post-menopausal women: findings from the Women's Health Initiative. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 835. doi:10.1158/1538-7445.AM2015-835

Hormone Use, Reproductive History, and Risk of Lung Cancer: The Women’s Health Initiative Studies

Results from the Women's Health Initiative clinical trials demonstrated no increase in the risk of lung cancer in postmenopausal women treated with hormone therapy (HT). We conducted a joint analysis of the Women's Health Initiative observational study data and clinical trials data to further explore the association between estrogen and estrogen-related reproductive factors and lung cancer risk. Reproductive history, oral contraceptive use, and postmenopausal HT were evaluated in 160,855 women with known HT exposures. Follow-up for lung cancer was through September 17, 2012; 2467 incident lung cancer cases were ascertained, with median follow-up of 14 years. For all lung cancers, women with previous use of estrogen plus progestin of less than 5 years (hazard ratio = 0.84; 95% confidence interval = 0.71-0.99) were at reduced risk. A limited number of reproductive factors demonstrated associations with risk. There was a trend toward decreased risk with increasing age at menopause (ptrend = 0.04) and a trend toward increased risk with increasing number of live births (ptrend = 0.03). Reduced risk of non-small-cell lung cancer was associated with age 20-29 years at first live birth. Risk estimates varied with smoking history, years of HT use and previous bilateral oophorectomy. Indirect measures of estrogen exposure to lung tissue, as used in this study, provide only weak evidence for an association between reproductive history or HT use and risk of lung cancer. More detailed mechanistic studies and evaluation of risk factors in conjunction with estrogen receptor expression in the lung should continue as a role for estrogen cannot be ruled out and may hold potential for prevention and treatment strategies.

Reproductive Factors, Hormone Use, and Risk for Lung Cancer in Postmenopausal Women, the Nurses' Health Study

There is increasing evidence suggesting that female hormones may play a significant role in lung cancer development. We evaluated the associations between reproductive factors, exogenous hormone use, and lung cancer incidence in the Nurses' Health Study. We assessed age at menopause, age at menarche, type of menopause, parity, age at first birth, postmenopausal hormone (PMH) use, and past oral contraceptive use in 107,171 postmenopausal women. Cox models were used to estimate the hazard ratios for each exposure, adjusting for smoking and other covariates. We identified 1,729 lung cancer cases during follow-up from 1984 to 2006. Menopause onset before 44 years of age (hazard ratio, 1.39; 95% confidence interval, 1.14-1.70) and past oral contraceptive use for >5 years (hazard ratio, 1.22; 95% confidence interval, 1.05-1.42) were associated with increased lung cancer risk. These associations were strongest in current smokers and small cell histology. In never smokers, increased parity was associated with decreased risk among parous women (P trend = 0.03), whereas in current smokers, older age at first birth was associated with increased risk (P trend = 0.02). PMH use was not associated with overall lung cancer incidence. However, nonsignificant results of increased risk in adenocarcinoma were seen with current PMH use. Our findings suggest female hormones may influence lung carcinogenesis, although the effect is likely modest, varied by histologic subtype, and altered by smoking. Further investigation of the pathophysiology of female hormones in lung cancer subtypes and their interaction with smoking will lead to better understanding of lung carcinogenesis.

Estrogen plus progestin increased lung cancer mortality but not incidence in postmenopausal women

Source Citation Chlebowski RT, Schwartz AG, Wakelee H, et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of a randomised...

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

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

Hormone replacement therapy and survival in lung cancer in postmenopausal women in a rural population

Hormone replacement therapy (HRT) may play a role in the development of lung cancer and subsequent survival. Results from studies exploring these issues are inconsistent. A retrospective study in a rural population was conducted to determine whether a history of HRT use is associated with survival of postmenopausal women with lung cancer. A retrospective medical chart review of 648 postmenopausal women, diagnosed with a first primary lung cancer between 1995 and 2005, was conducted in a regional hospital in Paducah, Kentucky. History of HRT use was collected. Log-rank test and multivariate Cox regression analysis were performed to examine the effects of HRT on survival. The median survival for women with a history of HRT use was 16.4 months, compared with 10.5 months for women without a history of HRT use. However, this difference in survival was not statistically significant (hazard ratio, 1.09; 95% confidence interval, 0.82-1.44). Women with a history of HRT use were younger on average (64.3 years) at diagnosis than women without a history of HRT use (69.5 years, P<.01). Cigarette smoking was adversely associated with survival (P=.03), as were age (P<.01) and TNM stage (P<.01). In contrast to previous studies, within this population, a history of HRT use in postmenopausal lung cancer patients was not associated with decreased survival. Because most of the published studies on this issue are retrospective, the discrepant findings reflect the complexity of the role of HRT use in the survival of lung cancer patients.

A prospective study of reproductive factors, hormone use, and risk of lung cancer in postmenopausal women

1501 Background: There has been increased interest in understanding the role of hormonal factors in lung cancer (LC) in women with the observation that it exhibits different epidemiologic patterns and treatment response when compared to men. However, results of published studies have been inconsistent, possibly due to inadequate smoking adjustment. Methods: We prospectively examined the associations between reproductive factors, exogenous hormone use, and LC incidence in 106,574 postmenopausal women in the Nurses’ Health Study. Participants completed biennial questionnaires which included updated smoking history. We assessed age at menopause, age at menarche, type of menopause, parity, postmenopausal hormone (PMH), and oral contraceptive use. Cox proportional hazards modeling was used to estimate the relative risks (RR) of each exposure, adjusted for smoking status, number of cigarettes, time since quitting, age of initiating smoking, fruit/vegetable intake, body mass index, and environmental smoking exposure. Results: We identified 1,565 LC cases during follow up from 1984 to 2004. Parity was associated with decreased LC risk in never smokers (RR = 0.54, 95% CI 0.31–0.96) but increased risk in current smokers (RR = 1.44, 95% CI 1.03–2.02). No association was seen in former smokers. Also, younger age at menopause was associated with higher LC risk in women with natural menopause (p-trend = 0.016). PMH use was not associated with LC incidence. The RR for current PMH users was 1.01 (95% CI 0.87–1.17) and for past users was 0.95 (95% CI 0.82–1.1). No significant association was seen when assessed by duration of PMH use, time since last use, or type of PMH. However, past use of oral contraceptives for greater than 5 years was associated with increased LC risk (RR = 1.2, 95% CI 1.03–1.41). Conclusions: These results suggest that there may be an association between hormonal factors and LC development, and further suggest that the mechanism may differ in smokers versus lifelong never smokers. No significant financial relationships to disclose.

Expression of aromatase CYP19 and its relationship with parameters in NSCLC

Human aromatase (CYP19) responsible for the conversion of androgens to estrogens is expressed not only in gonads and adrenals but also in many other tissues, including normal lungs and lung cancers. To investigate the involvement of CYP19 in lung cancer development, purified CYP19 protein and antibody are required. In this study, we have developed an efficient expression method of human aromatase in E. coli (>1000 nmol/L culture). The protein purified from E. coli was used to raise an antibody against the human CYP19 in rabbits. The resulting antibody showed a high titer judged by ELISA, which allowed us to determine the expression of CYP19 in non-small cell lung cancer (NSCLC). Of 78 NSCLC specimens from Japanese patients, 50 (64%) NSCLC aberrantly expressed CYP19. This CYP19 expression in NSCLC was independent of any clinical and pathological parameters as well as the expression of other P450s, except tumor stage. The results suggest that the aromatase inhibitors might be useful for the management of non-small cell lung cancer in postmenopausal women.

Hormone Replacement Therapy as a Risk Factor for Non-Small Cell Lung Cancer: Results of a Case-Control Study

Purpose: It was the aim of this study to assess the risk of lung cancer in postmenopausal women who received hormone replacement therapy (HRT). Experimental Design: This case-control study involves women who received medical services at Roswell Park Cancer Institute (RPCI) in Buffalo, New York, between 1982 and 1998, and who agreed to complete an epidemiological questionnaire. Participants with missing smoking data were excluded. The case group consisted of 595 women with primary lung cancer. Controls included 1,195 women, randomly selected from a pool of 5,845 eligible individuals, who received medical services at RPCI for non-neoplastic conditions; they had come to RPCI with a suspicion of neoplastic disease, but were diagnosed with neither benign nor malignant conditions. Controls were frequency matched 2:1 to cases on 5-year age intervals and exposure to smoking (ever/never). Cases and controls were comparable for age (means 61.3 and 61.0 years) and ever smoking (90%). Results: There were more former smokers among the cases (67 vs. 59% in controls); cases were less likely to be high school educated, were thinner, and were less likely to report HRT use compared with controls. Overall, hormone use was associated with a significant reduction in risk of lung cancer (adjusted odds ratio = 0.67; 95% confidence interval 0.53–0.85). Stratified analyses showed significant reductions in lung cancer risk in former smokers and women with normal to low body mass index. Conclusion: This study supports the hypotheses that there is a protective effect of HRT use on lung cancer risk in women.

O-052 Hormone replacement therapy and the risk of lung cancer in post-menopausal women

O-052 Hormone replacement therapy and the risk of lung cancer in post-menopausal women

92330928 Alcohol, beer, and lung cancer in postmenopausal women: The Iowa Women's Health Study

92330928 Alcohol, beer, and lung cancer in postmenopausal women: The Iowa Women's Health Study

Alcohol, beer, and lung cancer in postmenopausal women. The Iowa Women's Health Study.

There are data to suggest a relationship between alcohol consumption, particularly beer, and lung cancer. This hypothesis was tested on data from a cohort of 41,837 Iowa women aged 55 to 69 years. Women were recruited by mail and provided information on alcohol and tobacco use, physical activity, and education. Compared to a randomly selected group of women without lung cancer (n = 1900), those with lung cancer (n = 109) consumed more alcohol (measured on the Willett food frequency questionnaire) (10.2 versus 3.6 g/d; P = 0.001). The difference was accounted for largely by differences in beer consumption (3.5 versus 0.6 glass/wk; P = 0.003). Liquor consumption by patients was about double that by control subjects (1.7 versus 0.8 glass/wk; P = 0.063). Wine consumption was low and did not differ between those with and those without lung cancer. The relationship between beer consumption and lung cancer risk appeared U-shaped. After adjusting for the other variables (including six categories of pack-years of smoking), beer consumption remained a significant predictor of lung cancer risk. Those drinking 1 or more beers per week had an odds ratio of 2.0 (95% confidence interval, 1.02 to 3.80) compared with those consuming less than 1 glass per week. There was no evidence of interaction with smoking. The association of beer with lung cancer does not appear to be explained solely by confounding with cigarette smoking, although that remains by far the single strongest predictor of risk.