Peter MacCallum Cancer Centre, Melbourne, Australia.
Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
Breast. 2017 Aug;34 Suppl 1:S27-S30. doi: 10.1016/j.breast.2017.06.023. Epub 2017 Jun 28.
Triple negative breast cancer (TNBC) a clinically aggressive subtype of breast cancer with poor outcomes. Chromosomal instability is a hallmark of many TNBCs, and likely underlies its ability to adapt and rapidly become resistant to chemotherapy. A study of residual disease after neoadjuvant chemotherapy have identified biological mechanisms driving this resistance to chemotherapy. Copy number amplifications such as MCL1, MYC and JAK2, as well as PTEN deletions or mutations have all been identified at a higher frequency in residual disease, suggesting they may play a role in de novo or acquired chemotherapy resistance. Increased copy number and expression of the PIM1 proto-oncogene in TNBC has also been identified as a new target of chemotherapy resistance. However, given the genomic instability and subclonal nature of driver mutations in TNBC, single agent targeted therapy is unlikely to be effective. Lately immune evasion has also been identified as another key characteristic of poor prognostic and chemo-resistant primary TNBCs. Combinations of checkpoint inhibition with targeted therapy and/or chemotherapy are currently being investigated.
三阴性乳腺癌（TNBC）是一种临床侵袭性乳腺癌亚型，预后较差。染色体不稳定性是许多 TNBC 的标志，可能是其适应和迅速对化疗产生耐药性的基础。对新辅助化疗后残留疾病的研究已经确定了驱动这种化疗耐药性的生物学机制。在残留疾病中，MCL1、MYC 和 JAK2 等拷贝数扩增，以及 PTEN 缺失或突变的频率都更高，这表明它们可能在新辅助或获得性化疗耐药中发挥作用。在 TNBC 中 PIM1 原癌基因的拷贝数增加和表达增加也被确定为化疗耐药的新靶点。然而，鉴于 TNBC 中驱动突变的基因组不稳定性和亚克隆性质，单一靶向治疗不太可能有效。最近，免疫逃逸也被确定为预后不良和化疗耐药原发性 TNBC 的另一个关键特征。目前正在研究检查点抑制与靶向治疗和/或化疗的联合应用。
