Lung Cancer in Women

Abstract

Background: Lung cancer is the leading cause of cancer-related death for women in the United States. Clinical characteristics, histology, epidemiology, and treatment responses are unique for women with lung cancer.

Methods: A literature search of Medline publications from 1989 to 2021 was conducted for lung cancer in women. Subsequent narrative review focused on identified differences in risk factors, diagnosis, and treatment of importance to the surgical care of these patients.

Results: Studies investigating lung cancer in which sex differences were explored demonstrated differences in risk factors, histology, and treatment response among women, with a significant postsurgical survival advantage over men (41.8 months vs 26.8 months, P = .007) and greater clinical benefit from anti-PD-1 combined with chemotherapy (hazard ratio, 0.44; 95% confidence interval, 0.25-0.76) compared with men (hazard ratio, 0.76; 95% confidence interval, 0.64-0.91). Smoking remains a dominant risk factor, and multiple clinical trials suggest lung cancer screening provides greater benefit for women. However young nonsmoking patients with lung cancer are 2-fold more likely to be female, advocating for broader sex-based screening criteria. Potential roles of genetic mutations, estrogen signaling, and infectious elements in sex-based differences in presentation, histology, prognosis, and treatment response are explored.

Conclusions: Overall much remains unknown regarding how sex influences lung cancer risk, treatment decisions, and outcomes. However evidence of specific differences in presentation, environmental risk, molecular drivers, and mutational burden support the need to better leverage these sex-associated differences to further improve detection, diagnosis, surgical outcomes, and systemic regimens to advance the overall care strategy for women with lung cancer.