A Comprehensive Review on Multifaceted Mechanisms Involved in the Development of Breast Cancer Following Adverse Childhood Experiences (ACEs)

Background and aim of the work: Adverse Childhood Experiences (ACEs) may give rise to harmful effects on health throughout life. Epigenetic changes explain how preexisting risk factors may contribute to produce altered biological responses and cancer risk. The main aim of the review is to summarize studies examining the means in which Adverse Childhood Experiences (ACEs) can modulate individual vulnerability to breast cancer (BC) development through multifaceted mechanisms. Methods: Studies selection, data extraction, and assessments agreed to PRISMA criteria. We included original research with clinical samples following BC interventions, investigating potential mechanisms linking ACEs and BC in adults. Results: From the 3321 papers found, nine articles involving 2931 participants were selected. All studies included ACEs retrospective assessments and psychological measures, and seven of them considered biomarkers. Individuals exposed to greater ACEs were at increased BC risk compared with individuals with no ACEs. Associations were found between child abuse and/or neglect, depression, perceived stress, fatigue, and plasma levels of cytokines interleukin (IL-6), C-reactive protein (CRP), soluble tumor necrosis factor receptor type II (sTNF-RII), interleukin IL-1 receptor antagonist (IL-1ra), and psycho-physiological adjustments that may lead to BC. Conclusions: Exposure to multiple ACEs appears a risk factor for BC development in adulthood. Although the clinical relevance of findings such as this is ambiguous, the review added evidence for a link between the presence of childhood adversity and BC occurrence, pointing to psychological, hormonal, and immunological dysregulations.