Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
Departments of Pathology, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
Breast Cancer. 2019 Jan;26(1):47-57. doi: 10.1007/s12282-018-0888-y. Epub 2018 Jul 3.
Neoadjuvant chemotherapy (NAC) is the standard therapeutic strategy for triple-negative breast cancer (TNBC). TNBC patients with residual disease after NAC have a significantly worse survival than those with pathological complete response (pCR); however, there is no apparent prognostic factor for non-pCR patients. Cancer stemness or epithelial-mesenchymal transition (EMT) might influence the sensitivity to chemotherapy.
Forty-eight patients with TNBC who were treated with NAC were available were included in this study. The expressions of stemness marker CD44v9, EMT marker vimentin and BRCA1, and basal phenotype were evaluated with immunohistochemistry. The relationships between the expression of these proteins and the pCR rate and the prognosis, especially in the patients with residual tumors, were investigated.
Among the 48 patients, pCR was achieved in 14 cases. High nuclear grade and basal phenotype in the pre-NAC samples were significantly correlated with pCR (p = 0.0458 and 0.0343). There were no significant relationships between the pCR rate and the expression of CD44v9, vimentin, or BRCA1. Achieving pCR was significantly correlated with longer distant metastasis-free survival (DMFS) (p = 0.0206). High CD44v9 expression was significantly associated with shorter DMFS (p = 0.0291). Among the patients in whom pCR was not achieved, high grade in the residual tumor cells, poor pathological response and high CD44v9 expression in the pre-treatment CNB samples were significantly correlated with a poor DMFS (p = 0.0433, 0.0406 and p = 0.0333). In addition, high grade in the residual tumor cells was significantly associated with high CD44v9 expression in the pre-treatment CNB (p = 0.0389).
High CD44v9 expression in pre-NAC samples was associated with poor prognosis in TNBC patients treated with NAC, especially for those in whom pCR was not achieved.
新辅助化疗(NAC)是三阴性乳腺癌(TNBC)的标准治疗策略。NAC 后仍有残留病灶的 TNBC 患者的生存明显差于病理完全缓解(pCR)患者;然而,非 pCR 患者没有明显的预后因素。肿瘤干细胞或上皮-间质转化(EMT)可能影响对化疗的敏感性。
本研究纳入了 48 例接受 NAC 治疗的 TNBC 患者。采用免疫组织化学法检测干细胞标志物 CD44v9、EMT 标志物波形蛋白和 BRCA1 以及基底表型的表达。研究了这些蛋白的表达与 pCR 率及预后的关系,特别是在有残留肿瘤的患者中。
在 48 例患者中,有 14 例达到 pCR。新辅助化疗前样本的核高分级和基底表型与 pCR 显著相关(p=0.0458 和 0.0343)。pCR 率与 CD44v9、波形蛋白或 BRCA1 的表达无显著相关性。达到 pCR 与远处无转移生存(DMFS)显著相关(p=0.0206)。CD44v9 高表达与 DMFS 显著相关(p=0.0291)。在未达到 pCR 的患者中,残留肿瘤细胞的高分级、病理反应差和新辅助化疗前 CNB 样本中 CD44v9 高表达与 DMFS 差显著相关(p=0.0433、0.0406 和 p=0.0333)。此外,残留肿瘤细胞的高分级与新辅助化疗前 CNB 中 CD44v9 的高表达显著相关(p=0.0389)。
新辅助化疗前样本中 CD44v9 的高表达与接受 NAC 治疗的 TNBC 患者的不良预后相关,尤其是对未达到 pCR 的患者。