30 juli 2012: aan onderstaande informatie hebben we deze informatie van ASCO toegevoegd, een interview met een van de onderzoeksters van de Nurses health Study Christina Balk MD, MPH: Studies Reveal that Hormonal Factors Influence Lung Cancer Risk in Women A Conversation with Christina S. Baik, MD, MPH. Naar aanleidng van de studie
1. Baik CS, Strauss GM, Speizer FE, et al: Reproductive factors, hormone use, and risk for lung cancer in postmenopausal women, the Nurses’ Health Study. Cancer Epidemiol Biomarkers Prev 19:2525-2533, 2010. waarvan we het abstract onderaan hebben geplaatst. En bevestigt de conclusies uit onderstaande informatie dat longkanker bij vrouwen ook wordt beïnvloed door hormonen, bv. pilgebruik of hormoongebruik vooraf en tijdens de menopauze.
2 juni 2009: Bron: ASCO 2009
Twee grote studies tonen aan dat er een verband is tussen longkanker bij vrouwen en hormonale factoren. Uit de resultaten van de Women's Health Initiative (WHI) blijkt dat vrouwen die oestrogeen plus progestin hebben genomen een significant hogere kans hadden te sterven aan niet-kleincellige longkanker (NSCLC) dan vrouwen die niet de hormonen hadden genomen. Over het algemeen was er geen statistisch significant verschil in de incidentie van NSCLC in het hormoontherapie groep vergeleken met de placebo-groep; 96 patiënten (0,14%) die CEE plus MPA ontwikkelden NSCLC, in vergelijking met 72 patiënten (0,11%) die een placebo ( p = 0,12) hadden gekregen. Echter er werd een groot verschil waargenomen na 5 jaar, met meer diagnoses in de CEE-plus MPA groep. Bovendien, bij vrouwen die werden gediagnosticeerd met NSCLC was de mortaliteit 61% hoger voor degenen die hormoontherapie ontvingen in vergelijking met degenen die geen hormonen kregen (67 versus 39 doden, respectievelijk, p = 0,02).
Two large-scale studies provide increasingly convincing evidence that lung cancer is affected by hormonal factors, an issue that has been controversial for many years. During Saturday’s Cancer Prevention Oral Abstract Session, Rowan T. Chlebowski, MD, PhD, of Harbor-UCLA Medical Center, presented results from a secondary analysis of data from the Women’s Health Initiative (WHI) showing that women who took estrogen plus progestin for relieving symptoms of menopause had a higher mortality rate from non-small cell lung cancer (NSCLC) than women who did not take the hormones (Abstract CRA1500). Christina S. Baik, MD, MPH, of Tufts Medical Center, presented results from the Nurses’ Health Study (NHS) demonstrating that the risk of lung cancer may be increased by certain hormonal and reproductive factors but not by postmenopausal hormone use (Abstract 1501). Together with previous study data, the results of these studies illustrate lung cancer as a heterogeneous disease affected by numerous hormonal factors that warrant continued examination.
Dr. Chlebowski examined the incidence of NSCLC in 16,608 women enrolled in the WHI clinical trial and determined mortality rates in those who developed disease during the trial period (5.6 years) and during follow-up (2.4 years). Women in WHI were randomly assigned to daily conjugated equine estrogen (CEE) (0.625 mg) plus medroxyprogesterone acetate (MPA) (2.5 mg) or placebo. Although previous research had suggested hormones are relevant to development of NSCLC, this is the first study to examine this relationship in a randomized, controlled clinical trial.
Overall, there was no statistically significant difference in the incidence of NSCLC in the hormone therapy group compared with the placebo group; 96 patients (0.14%) who received CEE plus MPA developed NSCLC, compared with 72 patients (0.11%) who received placebo (p = 0.12). How-ever, a variance was observed after 5 years, with more diagnoses in the CEE plus MPA group. In addition, among women who were diagnosed with NSCLC, mortality was 61% higher for those who received hormone therapy compared with those who did not (67 vs. 39 deaths, respectively; p = 0.02).
Smoking further increased the risk of developing NSCLC. Among women who were current smokers and who received CEE plus MPA, the mortality rate from NSCLC was 3.14%, compared with 2.3% of current smokers in the placebo group. According to Dr. Chlebowski, this translates to a preventable death for 1 in 100 current smokers using combined hormone therapy in the trial. Therefore, it is recommended that current smokers should discontinue smoking or should carefully consider this increased mortality risk before beginning or continuing combined hormone therapy.
“Many women entering menopause have symptoms that make them consider hormone therapy,” said Dr. Chlebowski. “The link we describe between hormone therapy with CEE plus MPA and death from non-small cell lung cancer should influence discussions between physicians and women considering hormone therapy use, especially for those with a smoking history.”
Supporting Data for Risks, Protective Effects
The fact that hormones play a role in lung cancer is further supported by data presented by Dr. Baik from the NHS. The NHS, which began in 1976 in Channing Laboratory at Harvard Medical School, is still on-going and is one of largest prospective, observational cohort studies in the United States. Although a few earlier studies have evaluated hormonal risk factors in lung cancer, the current study of NHS data is the largest study to date, examining 107,171 women with 1,729 lung cancer cases.
Notably, associations were strongest among current smokers, in small cell histology, and in squamous cell to a lesser degree. No significant associations were seen with adenocarcinoma. These results suggest that endogenous hormonal exposure during a woman’s lifetime may have a protective effect against lung cancer development.
The use of postmenopausal hormone therapy did not result in a significant association with lung cancer overall, but when analyzed separately by histology, there was a trend for increased risk in adenocarcinoma as well as a decreased risk in small cell and squamous histology.
Dr. Baik stated that the results of this study indicate lung cancer is a heterogeneous disease with complex hormonal mechanisms in carcinogenesis, which may vary by histologic subtypes, smoking status, and other factors.
Discussant Jill Siegfried, PhD, of the University of Pittsburgh, provided context for the studies through a discussion of previously published data on lung cancer and hormonal factors. She enumerated evidence for sex differences and the role of hormones in lung cancer, including evidence of high estrogen levels being associated with tumor progression and poor outcome. Dr. Siegfried also noted that estrogen-receptor beta (ER-beta) expression occurs in up to 80% of NSCLC tumors. She shared some unpublished data of her own that indicate high ER-beta expression correlates with shorter overall survival, while progesterone receptor expression appeared to have a protective effect, noting that looking at one hormone system alone could confound our understanding of the effects of hormones in lung cancer.
In contrast to data showing the negative effect of estrogen after cancer diagnosis, other data suggests that estrogen present before cancer diagnosis may offer some protection against tumor development, as in Dr. Baik’s study. Hypotheses to explain the incongruities between protective effects of estrogen before diagnosis versus harmful effects after diagnosis are just beginning to be explored in her laboratory and in others, said Dr. Siegfried, though more extensive study is needed.
Reproductive Factors, Hormone Use, and Risk for Lung Cancer in Postmenopausal Women, the Nurses' Health Study
+ Author Affiliations
- Authors' Affiliations: 1Division of Hematology-Oncology, Tufts Medical Center; 2Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; 3Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts
- Corresponding Author:
Christina S. Baik, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N/M3-A410, P.O. Box 19024, Seattle, WA 98109. Phone: 857-998-2861 and 206-667-2975; Fax: 206-667-4142. E-mail: firstname.lastname@example.org and email@example.com
Note: Presented in part at the American Society of Clinical Oncology Annual Meeting, 2009, Orlando, Florida.
Background: 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.
Methods: 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.
Results: 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.
Conclusions: Our findings suggest female hormones may influence lung carcinogenesis, although the effect is likely modest, varied by histologic subtype, and altered by smoking.
Impact: 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. Cancer Epidemiol Biomarkers Prev; 19(10); 2525–33. ©2010 AACR.
- Received April 30, 2010.
- Revision received July 20, 2010.
- Accepted July 21, 2010.
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