Expression and clinical implications of estrogen receptors in thoracic malignancies: a narrative review

Thoracic malignancies represent a significant global health burden with incidence and mortality increasing year by year. Thoracic cancer prognosis and treatment options depend on several factors, including the type and size of the tumor, its location, and the overall health status of patients. Gender represents an important prognostic variable in thoracic malignancies. One of the greatest biological differences between women and men is the presence of female sex hormones, and an increasing number of studies suggest that estrogens may play either a causative or a protective role in thoracic malignancies. Over the past 60 years since the discovery of the first nuclear estrogen receptor (ER) isoform α and the almost 20 years since the discovery of the second estrogen receptor, ERβ, different mechanisms governing estrogen action have been identified and characterized. This literature review reports the published data regarding the expression and function of ERs in different thoracic malignancies and discuss sex disparity in clinical outcomes. From this analysis emerges that further efforts are warranted to better elucidate the role of sex hormones in thoracic malignancies, and to reduce disparities in care between genders. Understanding the mechanisms by which gender-related differences can affect and interfere with the onset and evolution of thoracic malignancies and impact on response to therapies could help to improve the knowledge needed to develop increasingly personalized and targeted treatments.