Night shift work and breast cancer: from etiopathology to precision risk analysis

The increasing prevalence of night shift work (NSW) in our current professional landscape has raised significant public health concerns, particularly regarding its potential role in breast cancer (BC) development among women. Recognized by the International Agency for Research on Cancer (IARC) as a probable human carcinogen, NSW is believed to contribute to carcinogenesis primarily through circadian disruption induced by exposure to light at night. This review explores three key areas: (1) the biological mechanisms potentially linking NSW to BC, including melatonin suppression, oxidative stress, immune dysregulation, chronic inflammation, clock gene alterations, epigenetic modifications, telomere shortening, estrogen signaling disruption, vitamin D deficiency, and gut microbiome imbalance; (2) the emergence of novel putative biomarkers with might be relevant to early detection and precision risk analysis; and (3) the latest epidemiological evidence from case-control and cohort studies evaluating BC risk in female night shift workers, while considering the heterogeneity caused by exposure misclassification and other confounding factors. Altogether, these insights underscore the importance of integrating mechanistic, molecular, and epidemiological data, not only to deepen our understanding of the strength and nature of the relationship between NSW and BC, but also to support a precision medicine framework. This integrated approach is essential for improving individual risk stratification, guiding occupational health policies, and developing targeted preventive strategies for high-risk workers.