Role of phthalates in breast cancer initiation, progression and drug rersistance: A scoping review and recommendations

Phthalates are endocrine-disrupting chemicals (EDCs) with implications in breast cancer (BC). This review synthesizes epidemiological and experimental data to evaluate the role of phthalates in BC initiation, progression, and therapeutic resistance. We performed a scoping review using bibliographic citations from PubMed, Clinical Trials.gov, Embase, Cochrane Library, and Web of Science databases. MeSH terms for breast cancer and phthalates were combined and not restricted to the English language. The search was performed from 2010 to July 2024. The primary outcome was to determine the role of phthalates in BC. Two hundred and forty-seven articles were screened from 2010 to 2024. Of the 90 studies included, 23 were reviews, 24 were epidemiologic and 43 were experimental. Epidemiological evidence is mixed, with certain studies identifying a correlation between high cumulative exposure to specific phthalates, such as dibutyl phthalate, and increased BC risk, particularly in estrogen receptor-positive subtypes. Conversely, other studies reported no significant associations. Experimental investigations have demonstrated that phthalates disrupt estrogenic signaling, induce BC cell proliferation, and potentiate metastasis. Additionally, phthalates contribute to chemoresistance by modulating drug metabolism and altering gene expression. Given the persistent exposure to phthalates this review calls for public health interventions and recommendations.