Assessing Lead Exposure by Biological Matrices Analysis and Links to Breast Cancer: A Critical Review of Experimental and Epidemiological Findings

Lead (Pb), a ubiquitous environmental contaminant, is a toxic heavy metal known to interfere with enzymatic and hormonal processes. Its classification as a probable human carcinogen by international agencies has raised concerns about its potential role in cancer, including breast cancer (BC). This review critically examines epidemiological and experimental evidence linking Pb exposure to BC, emphasizing the impact of biological matrices used for Pb measurement on the consistency of findings. A systematic review following PRISMA guidelines was conducted. Eligible studies quantified Pb in breast tissues, blood, urine, hair, or toenails and assessed its association with BC risk. Animal studies and non-English publications were excluded. Twenty-seven studies (described in 23 publications) quantified Pb in human biological matrices: breast tissue (<i>n</i> = 6), urine (<i>n</i> = 6), blood (<i>n</i> = 9), hair (<i>n</i> = 4), and toenail (<i>n</i> = 2). Among them, 16 reported a positive association between Pb and BC risk (breast tissues: 4; urine: 3; blood: 6; hair: 3; toenails: 0). By contrast, 11 studies found no significant correlation (breast tissues: 2; urine: 3; blood: 3; hair: 1; toenail: 2). Four studies quantified Pb in different matrices, and the same results were obtained from analyses of breast tissue, blood, and hair. Discrepancies across studies included small sample sizes, heterogeneous demographic characteristics, insufficient follow-up, and different Pb assessment methods. While the majority of studies suggest a potential link between Pb exposure and BC, significant heterogeneity in study design and population selection limits definitive conclusions. Future research should standardize Pb measurement protocols in selected populations and explore mechanistic pathways to clarify this potential association and improve prevention strategies.