Triple-negative breast cancer (TNBC) is a broad collection of breast cancer that tests negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein. TNBC is considered to have poorer prognosis than other types of breast cancer because of a lack of effective therapeutic targets. The success of precision cancer therapies relies on the clarification of key molecular mechanisms that drive tumor growth and metastasis; however, TNBC is highly heterogeneous in terms of their cellular lineage composition and the molecular nature within each individual case. In particular, the rare and sometimes slow cycling cancer stem cells (CSCs) can provide effective means for TNBC to resist various treatments. Single cell analysis technologies, including single-cell RNA-seq (scRNA-seq) and proteomics, provide an avenue to unravel patient-level intratumoral heterogeneity by identifying CSCs populations, CSC biomarkers and the range of tumor microenvironment cellular constituents that contribute to tumor growth. This review discusses the emerging evidence for the role of CSCs in driving TNBC incidence and the therapeutic implications in manipulating molecular signaling against this rare cell population for the control of this deadly disease.

三阴性乳腺癌 (TNBC) 是一组广泛的乳腺癌，其雌激素受体 (ER)、孕酮受体 (PR) 和过量的人表皮生长因子受体 2 (HER2) 蛋白均呈阴性。由于缺乏有效的治疗靶点，TNBC 被认为比其他类型的乳腺癌预后更差。精准癌症治疗的成功依赖于阐明驱动肿瘤生长和转移的关键分子机制；然而，就其细胞谱系组成和每个病例中的分子性质而言，TNBC 具有高度异质性。特别是稀有的、有时是缓慢循环的癌症干细胞（CSCs）可以为TNBC提供有效的手段来抵抗各种治疗。单细胞分析技术，包括单细胞 RNA-seq (scRNA-seq) 和蛋白质组学，通过识别 CSC 群、CSC 生物标志物和有助于肿瘤生长的肿瘤微环境细胞成分的范围，为揭示患者水平的肿瘤内异质性提供了一条途径。本综述讨论了 CSC 在推动 TNBC 发病率中的作用的新证据，以及在操纵针对这种稀有细胞群的分子信号传导以控制这种致命疾病的治疗意义。