An Overview of Lung Cancer in Women and the Impact of Estrogen in Lung Carcinogenesis and Lung Cancer Treatment

Abstract

Lung cancer incidence and mortality have significantly increased in women worldwide. Lung adenocarcinoma is the most common form of lung cancer globally. This type of lung cancer shows differences by sex, including the mutational burden, behavior, clinical characteristics, and response to treatment. The effect of sex on lung cancer patients' survival is still controversial; however, lung adenocarcinoma is considered a different disease in women and men. Moreover, lung adenocarcinoma is strongly influenced by estrogen and is also different depending on the hormonal status of the patient. Young pre-menopausal women have been explored as an independent group. They presented in more advanced stages at diagnosis, exhibited more aggressive tumors, and showed poor survival compared to men and post-menopausal women, supporting the role of sex hormones in this pathology. Several reports indicate the estrogen's role in lung carcinogenesis and tumor progression. Thus, there are currently some clinical trials testing the efficacy of antihormonal therapy in lung cancer treatment. This mini review shows the updated data about lung cancer in women, its characteristics, the etiological factors that influence carcinogenesis, and the critical role of estrogen in lung cancer and treatment.

Keywords: adenocarcimoma; antiestrogen medication; estrogens; lung cancer; women.

Figure 1

Estrogen pathway in lung carcinogenesis and its relevance on therapy. Through non-genomic and genomic pathways, estrogen promotes cell proliferation, tumor growth, angiogenesis, cell migration, immunosuppressive responses, and tumor progression since tumor cells overexpressed ERβ. ARO expression maintains elevated E2 levels. The functional relationship between EGFR/EGF and E2/ER pathways sustain the E2 production through ARO expression and the EGFR activation in EGF absence. Preclinical studies have shown antiestrogen treatment efficacy, and in clinical trials, antiestrogen drugs have improved the clinical benefits of TKI and chemotherapy.