New breast cancer (BC) diagnoses will soon reach 2.5–3 million/year worldwide, with 15–25% of them being triple-negative breast cancer (TNBC), the most aggressive type, characterized for lacking the main pharmacological targets: estrogen and progesterone receptors (ERs and PRs), as well as HER2 overexpression. Therefore, chemotherapy remains the almost-unique systemic treatment for TNBC. However, some targeted therapies are recommended for use in combination with chemotherapy; namely, PARP inhibitors for BRCA-mutated TNBC, the immune checkpoint inhibitors pembrolizumab and atezolizumab, as well as the antibody–drug conjugates sacituzumab govitecan and trastuzumab deruxtecan, the latter for HER2low subtypes. Regardless of the limited benefits they provide, other treatments with similar mechanisms of action are being investigated in advanced clinical stages. Further, therapies that benefit other cancers, like PI3K/Akt/mTOR pathway and CDK4/6 inhibitors, are still being investigated for TNBC, although convincing results have not been obtained. Given this scenario, it might appear innovation for TNBC treatments has become stuck. However, the huge unmet medical need drives intense research into the biology of the disease. As a result, emerging disruptive therapies are being tested in early-stage trials, designed for novel targets and applying cutting-edge advances in immunotherapy and precision oncology.
全球范围内，每年新确诊的乳腺癌病例即将达到250万至300万例，其中15%至25%为三阴性乳腺癌。作为最具侵袭性的亚型，该类型乳腺癌的特征是缺乏主要药物治疗靶点——雌激素受体、孕激素受体以及HER2过表达。因此，化疗仍是三阴性乳腺癌几乎唯一的全身性治疗方案。然而，部分靶向疗法被建议与化疗联合使用：针对BRCA突变型三阴性乳腺癌的PARP抑制剂、免疫检查点抑制剂帕博利珠单抗和阿替利珠单抗，以及抗体偶联药物戈沙妥珠单抗和德曲妥珠单抗（后者适用于HER2低表达亚型）。尽管现有疗法获益有限，其他具有相似作用机制的疗法正在高级临床试验阶段接受评估。此外，对PI3K/Akt/mTOR通路抑制剂和CDK4/6抑制剂等已在其他癌症中显示疗效的疗法，针对三阴性乳腺癌的研究仍在持续，但尚未获得令人信服的结果。在此背景下，三阴性乳腺癌的治疗创新似乎陷入停滞。然而，巨大的未满足临床需求推动着对该疾病生物学机制的深入研究。基于此，针对新型靶点、融合免疫治疗与精准肿瘤学前沿进展的突破性疗法正在早期试验阶段接受验证。
肿瘤(癌症)患者之家