Margie L. Clapper, PhD, Deputy Scientific Director

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Estrogen and Lung Cancer: Researchers discover a new link

Here’s a shocking statistic: In the United States, about 20% of women and 10% of men diagnosed with lung cancer have never smoked.

It’s true that smoking remains the number one cause of lung cancer. But, because people who’ve never smoked now make up such a significant portion of lung cancer diagnoses, researchers are beginning to hone in on other risk factors.

One of those risk factors could be estrogen, according to emerging data from Fox Chase Cancer Center researchers Margie Clapper, PhD, and Jing Peng, PhD.

A New Research Focus

In a recent study published in the journal Oncotarget, Clapper, Deputy Scientific Director and Co-leader of the Cancer Prevention and Control Program at Fox Chase, and Peng, a research associate, found that the human lung can metabolize estrogen.

“Our finding underscores the importance of understanding and treating lung cancer as a disease with more than one cause,” said Clapper, the lead author on this study. “While it is true that smoking tobacco is the top risk factor for lung cancer, a substantial number of people receive a diagnosis despite having never smoked.”

Estrogen has long been linked to increased risk of breast and endometrial cancers, but this new study is the first to demonstrate the ability of the human lung to convert the hormone into numerous metabolites, yielding a carcinogenic derivative.

“The research also shows that the production of the carcinogenic estrogen metabolite varies with race, ethnicity, sex, and smoking status,” Peng said.

“While estrogen metabolites were detected within the lungs of both men and women, men had lower levels, as expected,” Peng said. “Chinese-American women produced more of this so-called ‘bad’ estrogen than non-Hispanic white women, which makes sense as Chinese never-smoking women have much higher rates of lung cancer than never-smoking European and Caucasian women.”

New Clinic Opening at Fox Chase

In an effort to understand why so many non-smoking women are being diagnosed with lung cancer, Fox Chase opened a first-of-its-kind Never Smokers Lung Cancer Clinic. The clinic is recruiting patients and is open to women, particularly Asian women, who:

  • Have never smoked
  • Have metastatic lung cancer
  • Have tried immunotherapy unsuccessfully

“Our new clinic specifically addresses the needs of people who have never smoked, which is important because they need different treatments,” said Joseph Treat, MD, a medical oncologist and a professor in the Department of Hematology/Oncology at Fox Chase.

“Many have certain mutations, such as EGFR – a common mutation seen in never-smokers – that tend to be responsive to particular treatments but not to others, such as immunotherapy,” Treat said.

Together surgical, medical, and radiation oncologists, as well as pulmonologists, work with researchers like Clapper and Peng in a multidisciplinary approach to identify possible risk factors for lung cancer, and develop better screening and treatment options. In addition to providing support, the new clinic aims to enroll patients in Clapper’s ongoing clinical research studies.

“This is just one foundational approach we are looking into at Fox Chase,” Treat said. “We have good treatment options for never-smokers who develop lung cancer and, with our new lung cancer clinic for never-smokers, we plan to develop additional strategies.”

Learn more about lung cancer treatment at Fox Chase.