Breast cancer, the most prevalent cancer affecting women worldwide, poses a significant cardio-oncological burden. Despite advancements in novel therapeutic strategies, anthracyclines, HER2 antagonists, and radiation remain the cornerstones of oncological treatment. However, each carries a risk of cardiotoxicity, though the molecular mechanisms underlying these adverse effects differ. Common mechanisms include DNA damage response, increased reactive oxygen species, and mitochondrial dysfunction, which are key areas of ongoing research for potential cardioprotective strategies. Since these mechanisms are also essential for effective tumor cytotoxicity, we explore tumor-specific effects, particularly in hereditary breast cancer linked to BRCA1 and BRCA2 mutations. These genetic variants impair DNA repair mechanisms, increase the risk of tumorigenesis and possibly for cardiotoxicity from treatments such as anthracyclines and HER2 antagonists. Novel therapies, including immune checkpoint inhibitors, are used in the clinic for triple-negative breast cancer and improve the oncological outcomes of breast cancer patients. This review discusses the molecular mechanisms underlying BRCA dysfunction and the associated pathological pathways. It gives an overview of preclinical models of breast cancer, such as genetically engineered mouse models, syngeneic murine models, humanized mouse models, and various in vitro and ex vivo systems and models to study cardiovascular side effects of breast cancer therapies. Understanding the underlying mechanism of cardiotoxicity and developing cardioprotective strategies in preclinical models are essential for improving treatment outcomes and reducing long-term cardiovascular risks in breast cancer patients.

乳腺癌是影响全球女性最普遍的癌症，对心脏肿瘤造成了沉重的负担。尽管新的治疗策略取得了进展，但蒽环类药物、HER2 拮抗剂和放疗仍然是肿瘤治疗的基石。然而，每种都存在心脏毒性的风险，尽管这些不良反应背后的分子机制不同。常见机制包括 DNA 损伤反应、活性氧增加和线粒体功能障碍，这些是正在进行的潜在心脏保护策略研究的关键领域。由于这些机制对于有效的肿瘤细胞毒性也是必不可少的，因此我们探讨了肿瘤特异性作用，特别是在与 BRCA1 和 BRCA2 突变相关的遗传性乳腺癌中。这些遗传变异损害了 DNA 修复机制，增加了肿瘤发生的风险，并可能增加蒽环类药物和 HER2 拮抗剂等治疗的心脏毒性。包括免疫检查点抑制剂在内的新型疗法在临床上用于治疗三阴性乳腺癌，并改善乳腺癌患者的肿瘤预后。本文讨论了 BRCA 功能障碍的分子机制和相关病理途径。它概述了乳腺癌的临床前模型，例如基因工程小鼠模型、同基因小鼠模型、人源化小鼠模型以及用于研究乳腺癌治疗心血管副作用的各种体外和离体系统和模型。了解心脏毒性的潜在机制并在临床前模型中开发心脏保护策略对于改善乳腺癌患者的治疗结果和降低长期心血管风险至关重要。