INTERNATIONAL CONGRESS OF
CancerGenetics
Epigenetic Links Between Chronic Stress, Emotional Regulation, and Molecular Pathways in Hereditary Breast Cancer: Novel Perspectives for Therapy and Prevention
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Sahar Masoomi,1,*
1. Researcher in Medical Genetics, Pharmacogenomics, Pharmaceutical Biotechnology, Translational Oncology, Psychoneuro-Oncology, Founder and Scientific Director of Sabrigen Research Initiative (Virtual Institute under development), Tehran, Iran
- Introduction: Breast cancer is the most prevalent and lethal type of cancer in women, profoundly impacting public health. While genetic factors such as BRCA1/2 mutations are recognized as primary risk contributors, accumulating evidence suggests that environmental and psychological factors, particularly chronic stress, can influence breast cancer onset and progression through epigenetic modifications. Recent studies have demonstrated that chronic stress can induce alterations in DNA methylation, chromatin remodeling, and histone modifications, thereby affecting the expression of cancer-related genes. These epigenetic changes can activate signaling pathways associated with cell proliferation, apoptosis resistance, and metastasis. In hereditary breast cancer, these modifications may synergize with pre-existing genetic mutations, further increasing tumor risk. Triple-negative breast cancer (TNBC), lacking estrogen, progesterone, and HER2 receptor expression, represents one of the most challenging subtypes in breast oncology. TNBC is characterized by aggressive progression, poor response to hormonal therapies, and high recurrence rates. Epigenetic alterations in TNBC, including hypermethylation of tumor suppressor genes and demethylation of oncogenes, play critical roles in molecular pathways regulating cellular growth and migration. Understanding these changes and their interaction with chronic stress and emotional regulation offers new opportunities for targeted therapies and epigenetic interventions. Moreover, emotional regulation has been identified as a protective factor against the adverse effects of stress. Individuals with higher emotional regulation capacity are less prone to stress-induced epigenetic alterations, consequently exhibiting reduced breast cancer risk. This review examines the epigenetic links between chronic stress, emotional regulation, and hereditary breast cancer, with a particular focus on TNBC. The aim is to identify shared molecular pathways and propose innovative strategies for breast cancer prevention and therapy emphasizing epigenetic modulation.
- Methods: This review examined studies published between 2019 and 2025 on epigenetic links between chronic stress, emotional regulation, and hereditary breast cancer, especially TNBC. Open-access articles from PubMed, Google Scholar, and PubMed Central were selected, including research and review articles. Data were analyzed to identify key epigenetic mechanisms, molecular pathways, and potential therapeutic targets.
- Results: Recent studies have provided critical insights into the epigenetic mechanisms associated with chronic stress, emotional regulation, and hereditary breast cancer, with a particular focus on triple-negative breast cancer (TNBC). DNA methylation profiling has revealed that hypermethylation of tumor suppressor genes such as BRCA1, TP53, and PTEN, along with hypomethylation of oncogenes such as MYC and KRAS, correlates with aggressive phenotypes and rapid tumor progression in TNBC patients. Histone modification analyses show significant alterations in H3K27me3, H3K9ac, and H3K4me3, affecting chromatin accessibility and gene expression patterns related to cell proliferation, apoptosis resistance, epithelial-mesenchymal transition (EMT), and metastasis. In addition to chronic stress, other psychological factors—including persistent negative affect and low satisfaction, depression, chronic sleep disturbances, long-term psychological tension, and chronic anxiety—are associated with epigenetic changes and may exacerbate tumorigenic pathways. These factors influence cancer progression via activation of the HPA axis, stress-responsive transcription factors, and regulation of genes involved in immunity and cell growth. Individuals with higher emotional regulation capacity exhibit a marked reduction in aberrant DNA hypermethylation and histone alterations, which correlates with lower TNBC prevalence and better prognostic indicators. Functional studies using patient-derived TNBC organoids have demonstrated that targeted interventions with epigenetic modulators such as DNMT and HDAC inhibitors can reverse oncogenic epigenetic marks induced by stress and other psychological disturbances, reducing cellular proliferation rates. These findings highlight shared molecular pathways linking chronic stress, persistent negative affect and low satisfaction, depression, chronic sleep disturbances, long-term psychological tension, chronic anxiety, and hereditary breast cancer, emphasizing epigenetic dysregulation as a modifiable risk factor. The results further suggest that combined psychological interventions and epigenetic therapies may be simultaneously effective in managing TNBC and improving patient prognosis.
- Conclusion: Current evidence highlights the central role of epigenetic mechanisms in linking chronic stress, emotional dysregulation, and other long-term psychological disturbances with hereditary breast cancer, particularly triple-negative subtypes. Epigenetic alterations in tumor suppressor genes and oncogenes interact with psychological factors and molecular pathways involved in cell growth and proliferation. These findings emphasize the importance of integrated therapeutic strategies, combining psychological support and epigenetic interventions, to mitigate the adverse effects of stress and psychological disturbances on cancer progression. Such combined approaches have the potential to improve patient prognosis, advance personalized medicine, and enhance comprehensive cancer care.
- Keywords: Epigenetics, Chronic Stress, Emotional Regulation, Hereditary Breast Cancer, Molecular Pathways
