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

Abstract

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.

Fig. 1. Schematic representation of night shift work as a contributor to breast cancer development.

The diagram illustrates the transition from a healthy breast to breast cancer, driven by chronic exposure to night shift work. Key biological mechanisms implicated in this process are reported. Selected elements adapted from Servier Medical Art (https://smart.servier.com, last accessed on 09 November 2025), licensed under Creative Commons Attribution 4.0 International License (CC BY 4.0; https://creativecommons.org/licenses/by/4.0/, last accessed on 09 November 2025).

Fig. 2. Immune cell populations modulated by night shift work.

Schematic representation of immune cell subsets affected by circadian disruption in night shift work. Each box depicts a cell type with altered functions and secreted molecules, including cytokines. Monocytes/macrophages: M2-like polarization. Basophils: acute mobilization. Neutrophils: systemic activation. CD8⁺/CD4⁺ T cells: reduced proliferation and activity. Treg cells: enhanced immunosuppression. NK cells: decreased cytotoxicity. Dendritic cells: impaired antigen presentation. B cells: diminished humoral response. These alterations promote chronic low-grade inflammation and reduced antitumor immune surveillance in long-term night shift work exposure. Selected elements adapted from Servier Medical Art (https://smart.servier.com, last accessed on 09 November 2025), licensed under Creative Commons Attribution 4.0 International License (CC BY 4.0; https://creativecommons.org/licenses/by/4.0/, last accessed on 09 November 2025).

Fig. 3. Night shift work-associated gene expression and DNA methylation changes in circadian clock genes.

Schematic representation of the core circadian clock feedback loops showing how night shift work alters clock gene expression and DNA methylation. A The CLOCK-BMAL1 complex activates PER and CRY transcription via E-box elements. B ROR and REV-ERB regulate BMAL1 expression through RRE sites. Red arrows indicate changes in gene expression, while red “M” denotes altered DNA methylation in clock genes, both associated with night shift work.

Fig. 4. Biological sampling and biomarker overview in female night shift workers.

The figure illustrates key sample types (blood, urine, saliva, stool, biopsy) and associated biomarkers, including indicators of oxidative stress, inflammation, immune function, endocrine disruption, circadian-relevant gene alterations (including clock genes and melatonin pathway genes), and gut microbiota imbalance. Selected elements adapted from Servier Medical Art (https://smart.servier.com, last accessed on 09 November 2025), licensed under Creative Commons Attribution 4.0 International License (CC BY 4.0; https://creativecommons.org/licenses/by/4.0/, last accessed on 09 November 2025).