Tumors formed by the unchecked growth of breast cells are known as breast cancer. The second most frequent cancer in the world is breast cancer. It is the most common cancer among females. In 2022, 2,296,840 women were diagnosed with breast cancer. The therapy of breast cancer is evolving through the development of Poly (ADP-ribose) polymerase (PARP) inhibitors, which are offering people with specific genetic profiles new hope as research into the disease continues. It focuses on patients with BRCA1 and BRCA2 mutations. This review summarizes the most recent research on the mechanisms of action of PARP inhibitors and their implications for breast cancer therapy. We review how therapeutic applications are developing and highlight recent studies showing the effectiveness of these medicines whether used alone or in combination. Furthermore, the significance of customized therapy is highlighted in enhancing patient outcomes as we address the function of genetic testing in identifying candidates for PARP inhibition. Recommendations for future research areas to maximize the therapeutic potential of PARP inhibitors are also included, along with challenges and limits in their clinical usage. The objective of this review is to improve our comprehension of the complex interaction between breast cancer biology and PARP inhibition. This knowledge will help to guide screening approaches, improve clinical practice, and support preventive initiatives for people at risk.

Breast cancer remains a leading cause of cancer-related mortality among women worldwide. Beyond classical estrogen receptor-alpha (ERα) and progesterone receptor (PR) signaling, tumor progression, invasion, and treatment resistance are increasingly linked to an interconnected endocrine–metabolic network involving insulin, insulin-like growth factors (IGF-1/IGF-2), thyroid hormones (T3/T4), catecholamines, adrenal steroids, prolactin, and growth hormone within the tumor microenvironment (TME). Following systematic searches of PubMed, Web of Science, and Scopus through September 2025, 141 primary and translational studies were evaluated in this narrative review. Evidence was categorized according to experimental context: in vitro models, animal xenografts and patient-derived xenografts, and human clinical or epidemiological studies. Endocrine–metabolic resistance was characterized as a mechanism through which tumor cells may circumvent ER/HER2-targeted therapies via hyperinsulinemia-associated insulin receptor/IGF-1R signaling, aerobic glycolysis, thyroid hormone-mediated receptor phosphorylation, and sympathetic/adrenergic remodeling of the TME. Hypoxia was associated with radioresistance, whereas reoxygenation enhanced radiosensitivity; trastuzumab emtansine (T-DM1) was recognized as having clinically relevant toxicities, including thrombocytopenia and hepatotoxicity; non-canonical progesterone signaling was considered in PR-negative and triple-negative breast cancer phenotypes; and PR downregulation was associated with anti-estrogen treatment. Resistance to single-receptor-targeted therapies may be promoted by redundant metabolic and neuroendocrine signaling. Improved therapeutic outcomes may require biomarker-guided combination strategies incorporating selective estrogen receptor degraders, CDK4/6, AKT, and PI3Kα inhibitors, antibody–drug conjugates, and metabolic interventions, including metformin and glycemic control.