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Breast cancer survivors who smoke, use hormones face higher lung cancer risk
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BARCELONA — Use of hormone replacement therapy may increase risk for lung cancer as a second primary malignancy among patients with breast cancer who smoke, according to study results presented at International Association for the Study of Lung Cancer World Conference on Lung Cancer.
“As we know, prior research indicates that women are more susceptible to cigarette-related lung carcinogenesis — there is evidence that it actually takes fewer cigarettes over a period of time to result in subsequent tumor growth in females compared with males,” Joseph N. Bodor, MD, PhD, fellow in the department of hematology/oncology at Fox Chase Cancer Center, said in an interview with HemOnc Today. “In addition, as a worldwide population, women are much more prone to never-smoking cancer. There are some disparities that we haven’t fully explained over time, and this has prompted many researchers to look at how hormonal factors and estrogen may be contributing.”
Bodor noted that research conducted by one of his collaborators motivated him to explore this topic further.
“Dr. Marge Clapper, a laboratory-based researcher, has been doing estrogen metabolism research for a long time,” he said. “She has looked at lung tumor tissue and has found that levels of the estrogen metabolite 4-hydroxylation of estrogen are higher in patients with lung cancer and in patients without cancer who smoke. She’s also demonstrated that cigarette smoke exposure upregulates the levels of 4-hydroxylation of estrogen. We hypothesized that because it took cigarette smoking in combination with estrogen to increase the risk for lung carcinogenesis, some of our laboratory research with 4-hydroxylation of estrogen may partially explain this relationship.”
Bodor and colleagues conducted a secondary analysis of the Women’s Health Initiative clinical trial and observational study cohorts, limiting the study population to women with a diagnosis of ductal carcinoma in situ or invasive breast cancer. The study included women aged 50 to 79 years enrolled between October 1993 and December 1998.
Lung cancer as a second primary malignancy served as the primary outcome. Researchers assessed predictor variables at baseline, including hormone replacement use, smoking history and reproductive factors.
Median follow-up was 13 years.
Among the 9,593 women with breast cancer, 120 were subsequently diagnosed with primary lung cancer. Median time to lung cancer diagnosis after initial breast cancer was 39.3 months (range, 0-148.8). Lung cancer subtypes included NSCLC-not otherwise specified (22%), adenocarcinoma (48%), squamous cell (15%), small cell (7%) and neuroendocrine (8%).
Although the researchers identified no independent correlation between hormone use and risk for lung cancer as a second primary malignancy, smoking at baseline was an independent predictor of risk (OR = 3.25; 95% CI, 1.62-6.51).
The multivariable logistical regression model also showed associations between second primary lung cancer risk and each year of age (OR = 1.03; 95% CI, 1.01-1.06) and current smoking plus current hormone use (OR = 2.75; 95% CI, 1.14-6.63).
Women who were current smokers and current hormone replacement users had a much higher risk for developing lung cancer as a second primary malignancy than those who were not current smokers and did not currently use hormone replacement (OR = 7.67; 95% CI, 4.47-13. 14).
“Breast cancer, especially when caught early, has a very good prognosis. There are a lot of women who are being effectively treated for breast cancer and being cured of it,” Bodor told HemOnc Today. “Thankfully, we have a large population of breast cancer survivors, and trying to keep them healthy over the long term is important. Smoking cessation, even after the patient has been treated for the breast cancer, is an important part of follow-up.” – by Jennifer Byrne
Reference:
Bodor JN, et al. Abstract OA09.05. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 7-10, 2019; Barcelona.
Disclosures: Bodor reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Narjust Duma, MD
Most never-smokers who get lung cancer are women, bringing attention to the fact that lung cancer may be a disease of women, with women having a higher predisposition to it. Adding the smoking factor worsens the situation.
We don’t know exactly how estrogens play a role in lung cancer; there have been two studies in addition to this on the subject. One showed that risk for lung cancer increases when a woman becomes postmenopausal. The question is, are they at higher risk because they are older, or because they have lower estrogen? Also, are patients with breast cancer at higher risk for lung cancer because they undergo chemotherapy or radiation or because they are estrogen-deprived?
Large randomized studies suggest that estrogen plus progestin therapy is associated with an increased risk for lung cancer and the presence of ERs in the lung tissue suggests a possible correlation between hormonal status and the development of lung cancer.
Every year we are seeing younger women being diagnosed with lung cancer. The incidence of lung cancer in non-Hispanic whites aged 30 to 49 years is now higher in women than in men. This reversal in trends is not accounted for by gender difference in smoking behaviors. So why are more younger women having lung cancer than before? Environmental factors like radon exposure could potentially play a role, in addition to hormonal factors with the increase use of hormonal birth control and changes in diets among younger women.
Lung cancer following a prior breast cancer history can be associated with the history of chemotherapy and radiotherapy, with the increase number of breast-conserving surgeries followed by radiation.
In summary, I’m reluctant to call it multifactorial, but it is.
It’s important to take away from this study that these women need to be watched. We watch them for 5 to 10 years after their diagnosis of breast cancer, but we don’t think about monitoring them for lung cancer. So, then they might survive one, but die of the other. In the United States, the No. 1 cause of cancer death is lung cancer, not breast cancer. Even if we catch it at an early stage, the surgeries are so large that women may end with long-term dyspnea. Lung cancer is a disease of women; it’s fairly multifactorial in this subgroup, but we need to continue working in changing the face of lung cancer.
University of Wisconsin Carbone Cancer Center
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