Endocrine disruption to metastasis: How phthalates promote breast carcinogenesis

Breast cancer is a leading cause of death in women worldwide. Data suggests that hereditary factors only account for 5-10 % of breast cancer incidence, resulting in increased concern regarding the carcinogenicity involved with environmental and lifestyle-related factors. Among these, phthalates - ubiquitous endocrine disrupting chemicals founds in plastics, cosmetics, and food packaging - pose a growing concern. Human exposure to phthalates occurs through ingestion, inhalation, dermal contact, and critical windows such as intrauterine development. As an endocrine-responsive organ, the breast is particularly susceptible to disruption by these compounds. This review highlights emerging evidence linking phthalate exposure to the initiation, progression, and metastasis of breast cancer. This comprehensive overview of carcinogenesis-promoting mechanisms of phthalates, involving estrogen receptor signaling, oncogenic pathway activation, promotion of cancer stemness, and induction of therapy resistance, will provide crucial insights into phthalate-driven mechanisms in breast cancer that can inform future research directions, public health strategies, and regulatory efforts aimed at mitigating environmental cancer risks.