Chronic psychosocial stress: a role in breast cancer etiology?

Epidemiological and preclinical studies are discrepant regarding the role of psychosocial stress in breast cancer (BC) development and metastasis. While no consensus has been reached based on epidemiological studies, preclinical rodent studies regularly employ chronic psychosocial stress paradigms to study mechanistic details in mammary carcinogenesis and metastasis. We aimed to review both epidemiological and preclinical studies of psychosocial stress in BC development, focusing on whether chronic psychosocial stress might be a particularly relevant stressor domain.

For in vivo preclinical rodent studies, we searched PubMed for individual studies from 1985 to December 2025 written in English that evaluated effects of chronic psychosocial stress on mammary tumorigenesis and metastasis. We restricted focus to studies that used chronic psychosocial stress protocols. For epidemiological research into psychosocial stress in BC, due to the abundant literature that spans several decades, we searched Medline (PubMed) for English-language systematic reviews and meta-analyses published in the last three decades (1995 to December 2025) in which participants were inquired about exposure to psychosocial stress.

Systematic literature searches identified 29 rodent studies that randomly allocated rodents to chronic psychosocial stress or safety. Twenty-five of the 29 studies found that chronic psychosocial stress increased mammary tumorigenesis and/or metastasis, with the remaining studies reporting more complex effects that reflected variations in study design elements. In contrast, most original research studies included in 14 systematic reviews and meta-analyses of epidemiological research focused on short-lasting, adverse life events, with no consistent associations detected with BC. Epidemiological studies have only partly and unsystematically addressed chronic psychosocial stress.

Findings from preclinical rodent studies indicate that chronic psychosocial stress may be a particularly relevant psychosocial exposure domain in BC development. In contrast, the epidemiological studies we reviewed focused predominantly on acute adverse life events, with limited attention to chronic psychosocial stress. We suggest that this evidence highlights the need to prioritize chronic psychosocial stress in future epidemiological studies of BC etiology. Actionable method components may include a life-course perspective for stress exposure, a multi-level social interaction perspective, inclusion of both chronic and acute stress and their interactions, and inclusion of individuals' subjective appraisals of distress.