Lung cancer in females—sex-based differences from males in epidemiology, biology, and outcomes: a narrative review

Background and Objective: The role of biological sex is seldom considered in characterizing lung cancer, the deadliest cancer in both the United States and the world. Lung cancer has traditionally been regarded as a male disease; as such, research in female-specific phenomena is frequently conflicting or absent. Currently, disparities in lung cancer incidence are primarily driven by females, especially non-smokers and those of younger age. This narrative review provides insight into sex-specific characteristics of lung cancer, highlighting risk factors, diagnosis patterns, carcinogenesis, and treatment outcomes in females. Methods: The PubMed database was searched on July 26, 2023 to identify research published between 2013 and 2023 in English. Sixty-three articles were considered relevant, and their full texts and citations were studied to compile information for this narrative review. Key Content and Findings: Exposure-related risk factors, including personal tobacco use, are thought to impact female lung cancer risk more profoundly. However, studies on occupational exposures are underpowered to conclude risk in females. Data characterizing the effect of endogenous and exogenous hormonal exposures on female lung cancer risk remain two-sided. Screening guidelines are tailored to white males, exacerbating sex and race disparities. The effect of biological sex on carcinogenesis and the immune system response to cancer is not fully understood, though the female immune system clearly reacts more aggressively to lung cancer. In early-stage disease, females have greater survival in the perioperative setting and during follow-up of several years, attributed to favorable histopathology and healthier baseline status. Sex-specific response to systemic treatment continues to be optimized as lack of standardization in randomized trials makes interpreting results difficult when aggregated. Conclusions: Biological sex plays a critical role in non-small cell lung cancer (NSCLC), though further study is needed to depict the complex web of factors that affect lung cancer risk, development, and outcomes. Female underrepresentation in studies has contributed to this lack of understanding. As these disparities are eliminated, we can move towards more effective treatment for both sexes in this pervasive yet deadly disease.