Dr Bodor on a Study Profiling Estrogen Species in Women With EGFR-Mutated NSCLC

J. Nicholas Bodor, MD, PhD, MPH, assistant professor, Department of Hematology/Oncology, Thoracic Oncology Program, Fox Chase Cancer Center, discusses the results of prior research supporting the inception of a study that profiled reactive estrogen species in women with EGFR-positive non–small cell lung cancer (NSCLC), as well as the findings from this study, which he presented during the 2023 IASLC World Conference on Lung Cancer.

This study investigated the hormonal factors that may contribute to lung cancer in women, specifically focusing on 2 catechol estrogens: 4-OHE and 2-OHE. 4-OHE is the putative carcinogen produced by CYP1B1. Prior studies have shown that 4-OHE can cause DNA damage and is linked with a higher risk of developing breast and uterine cancer. Additionally, previous research by Bodor and his colleagues demonstrated that 4-OHE may have oncogenic properties in normal human bronchial epithelial cells.

The other variety of catechol estrogen, 2-OHE, is produced by CYP1A1. The immunogenic potential of 2-OHE is less clear, although previous research indicates that this derivative could be converted by COMT into methoxy derivatives that may have antitumor and antiproliferative properties.

This study recruited 32 patients with EGFR-driven NSCLC from the Lung Cancer Clinic for Never-Smokers at Fox Chase Cancer Center, as well as 29 cancer-free women from the Fox Chase Cancer Center community. All patients were considered never smokers.

The hypothesis of this study, which mirrors hypotheses posed in prior studies, was that the ratio of 4-OHE to 2-OHE in a patient may be a helpful biomarker for assessing lung cancer risk, Bodor says. After all patients enrolled in the study were profiled, the investigators found evidence to support this hypothesis, Bodor explains. Women with EGFR-driven lung cancer had significantly greater levels of 4-OHE and significantly higher ratios of 4-OHE vs 2-OHE compared with women without cancer, Bodor concludes.