三阴性乳腺癌（TNBC）由于其异质性和侵袭性表型以及有限的靶向特异性治疗选择而成为主要的治疗挑战。滋养层细胞表面抗原 (Trop-2) 是一种在多种癌症中过度表达的跨膜糖蛋白，已成为 TNBC 的一个有前景的靶点。 Sacituzumab govitecan (SG) 是一种针对 Trop-2 的抗体药物偶联物 (ADC)，最近已进入晚期和转移性 TNBC 的治疗方案，与 Trop-2 表达状态无关，且毒性可控。尽管取得了令人印象深刻的结果，但有关其功效、安全性和 Trop-2 在癌症中的生物学作用的问题仍未解决。目前，Trop-2 不能被指定为 SG 治疗的预测生物标志物，尽管其表达与疾病结果相关，但其水平在所有 TNBC 中并不统一。此外，关于原发部位和转移部位的 Trop-2 表达变化及其与其他生物标志物相互作用的数据仍然不明确，但考虑到 SG 未来在其他适应症和环境中的应用，这些数据是强制性的。这就提出了在疾病早期阶段以及个性化和组合策略中仔细评估 SG 的功效和毒性特征的问题。必须提供研究和临床数据来解决 SG 的缺点并最大限度地减少其益处，以充分发挥其作为不同上皮肿瘤治疗剂的潜力。版权所有 © 2024 Rossi、Turati、Rosato 和 Carpanese。

Triple-negative breast cancer (TNBC) represents a major therapeutic challenge due to its heterogeneous and aggressive phenotype, and limited target-specific treatment options. The trophoblast cell surface antigen (Trop-2), a transmembrane glycoprotein overexpressed in various cancers, has emerged as a promising target for TNBC. Sacituzumab govitecan (SG), an antibody-drug conjugate (ADC) that targets Trop-2, has recently entered treatment algorithms for advanced and metastatic TNBC, independently from Trop-2 expression status, with manageable toxicity. Despite the impressive results, questions remain unsolved regarding its efficacy, safety profile, and Trop-2 biological role in cancer. Currently, Trop-2 cannot be designated as a predictive biomarker in SG treatment, albeit its expression correlates with disease outcome, yet its levels are not uniform across all TNBCs. Additionally, data regarding Trop-2 expression variations in primary and metastatic sites, and its interplay with other biomarkers are still ambiguous but mandatory in light of future applications of SG in other indications and settings. This poses the questions of a careful evaluation of the efficacy and toxicity profile of SG in such early stages of disease, and in personalized and combinatorial strategies. Research and clinical data are mandatory to address SG drawbacks and minimize its benefits, to realize its full potential as therapeutic agent in different epithelial tumors.Copyright © 2024 Rossi, Turati, Rosato and Carpanese.