The Women’s Health Initiative Studies, a large prospective study of lung cancer, found no strong associations between lung cancer risk and a wide range of reproductive history variables and only revealed weak support for the role of hormone use in the incidence of lung cancer. These findings were published in the Journal of Thoracic Oncology (2015; doi:10.1097/JTO.0000000000000558).

In the United States, 40% of the 160,000 deaths from lung cancer are women. In men, 90% of lung cancer deaths are associated with tobacco usage; however, in women, this number is approximately 75% to 80%. Female never-smokers are more likely to develop lung cancer than male never-smokers and the histologic subtype of lung cancer is different between men and women.

Women have a better prognosis with a 5-year survival rate of 20% compared with 15.4% for men. Given these gender differences, there is a need to understand the potential role of reproductive factors and hormone use in determining lung cancer risk for women.

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The Women’s Health Initiative Observational Study and Clinical Trials enrolled a geographically and ethnically diverse cohort of 161,808 postmenopausal women ages 50 to 79 years between 1993 and 1998 at 40 centers across the United States. Reproductive history, oral contraceptive use, and hormone therapy replacement was evaluated in the 160,855 women eligible to be included in the analysis. Incident lung cancer was observed in 2,467, and the median follow-up was 14 years.

The results show that women with previous use of estrogen plus progestin (less than 5 years) were at a slightly reduced risk for lung cancer. Increasing age at menopause trended towards reduced risk, whereas increasing number of children trended towards increased risk. Those who were ages 20 to 29 years at the birth of their first child had reduced risk of non-small cell lung cancer (NSCLC), but not all lung cancer. Risk estimates for hormone therapy usage and previous surgery to remove both ovaries varied with tobacco exposure history.

“Our study does not support the idea that reproductive history independently contributes to lung cancer risk, and recapitulates the inconsistent findings within epidemiologic literature on lung cancer risk and reproductive history measures,” concluded the authors.

“Likewise, the epidemiologic literature is also inconsistent with regard to the role of hormone use in lung cancer risk and the overall results presented by our study suggest that oral contraceptives and hormone therapy use are not associated with risk of lung cancer,” stated the authors.

The lead author, Ann G. Schwartz, MD, MPH, Deputy Center Director, Karmanos Cancer Institute, Wayne State University in Detroit, Michigan, cautioned that “questions remain about estrogen and lung cancer risk that will not easily be answered by studies focusing on hormone use and emphasizes that the interplay between cigarette smoking, estrogen, genetic susceptibility and lung cancer is complex and continued study is necessary to tease apart these relationships.”