Lung cancer in women in 21th century

Abstract

Lung cancer is the first cause of death from malignant disease. The distressing epidemiological data show the increasing female to male incidence ratio for this tumor. A high incidence of lung cancer in never smokers with importance of environmental agents makes a problem among women. Adenocarcinoma (ADC) is noted in women with increasing rate and ethnic background impacts female lung cancer with differences in the incidence of genetic aberrations. The conception of different hormonal status is taken into consideration as potential explanation of variant cancer biology and clinical manifestation in women and men. The impact of 17-β-estradiol, estrogen receptors, aromatase expression, pituitary sex hormones receptors in carcinogenesis with relation between estrogens and genetic aberrations are investigated. The response to newest therapies among female is also different than in men. This overview summarizes currently available evidence on the specificity of female lung cancer and presents the direction of necessary studies.

Keywords: EGFR mutation; Lung cancer; adenocarcinoma (ADC); estrogen; women.

Figure 1

Distribution of new cases and the deaths for three most common cancers in the World [2018] and in Poland [2014]. The pie charts present each cancer proportion of all cancers. (A) Global incidence, (B) global mortality, (C) incidence in Poland, (D) mortality in Poland. M, male; F, female (10,11).

Figure 2

The ratio women to men of age-standardized incidence rate in 2018 vs. 2008 in the different parts of the world. The arrows show increasing tendency of this ratio. Synthesis from numerous cited publications.

Figure 3

Estrogens in lung adenocarcinoma (ADC). The source of estrogens in lung environment is from circulation (B) or they are produced locally (A). The elevated level of E2 (17-β-estradiol) and overexpression of receptors to E2-ERα as well as aromatase (ARO) enzyme are involved in carcinogenesis in terminal airways and in tumor progression. There is association of thyroid transcription factor-1 (TTF-1) positivity with estrogen axis.

Figure 4

Lung cancer in women: what we know and what should we get to know. COPD, chronic obstructive pulmonary disease; E, estrogens; ETS, environmental tobacco smoke; ICIs, immune checkpoint inhibitors; TKIs, tyrosine kinase inhibitors; TMB, tumor mutational burden.