Sayed-Ahmed Mohamed Mohamed, Hafez Mohamed Mahmoud, Al-Shabanah Othman Abdualla, Al-Rejaie Salim Salih, Aleisa Abdulaziz Mohamed, Al-Yahya Abdulaziz Abdulrhman, Alsheikh Abdulmalik, Al Diab Abdurrahman Ibrahim, Al-Akeely Mohammad Hamad
Tumori. 2013 Jul-Aug;99(4):545-54. doi: 10.1177/030089161309900418.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2). Although TNBC represents only 15% of all types of breast cancer, it accounts for a large number of metastatic cases and deaths. Because of the high metastatic rate and both local and systemic recurrence associated with TNBC, extensive research efforts are actively looking for target therapies to effectively treat this aggressive disease. Accordingly, this study has been initiated to investigate the differential expression of biological markers in TNBC and non-TNBC Saudi women that might be utilized as potential targeted therapy and/or predict the sensitivity to currently available therapeutic regimens.
Two hundred formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues were selected and divided into 3 groups: benign breast tissues (20), TNBC tissues (80) and non-TNBC tissues (100). Expression of mRNA in FFPE tissues was analyzed using real-time polymerase chain reaction (RT-PCR) for the following genes: poly (ADP-ribose) polymerase 1 (PARP-1), topoisomerase 2A (TOPO-2A), vascular endothelial growth factor (VEGF), C-MYC, basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP-2 and MMP-9), human epidermal growth factor 1 (HER1) and multidrug resistance (MDR) genes.
In the TNBC group, expression of PARP-1, TOPO-2A, HER1, C-MYC, VEGF, bFGF and MMP-2 showed a highly significant increase compared to the non-TNBC group.
The results of this study suggest that (1) TNBC patients will benefit more from TOPO-2A inhibitors as well as antiangiogenic and antimetastatic therapies; (2) inhibition of these target genes is emerging as one of the most exciting and promising targeted therapeutic strategies to treat TNBC in which the intended targets are DNA repair, tumor angiogenesis and metastasis.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，缺乏激素受体和人表皮生长因子受体2（HER2）的表达。尽管TNBC仅占所有乳腺癌类型的15%，但它导致了大量的转移病例和死亡。由于TNBC的高转移率以及局部和全身复发，广泛的研究工作正在积极寻找有效的靶向治疗方法来治疗这种侵袭性疾病。因此，本研究旨在调查TNBC和非TNBC沙特女性中生物标志物的差异表达，这些生物标志物可能用作潜在的靶向治疗和/或预测对现有治疗方案的敏感性。
选取200例福尔马林固定、石蜡包埋（FFPE）的乳腺癌组织，分为3组：良性乳腺组织（20例）、TNBC组织（80例）和非TNBC组织（100例）。使用实时聚合酶链反应（RT-PCR）分析FFPE组织中以下基因的mRNA表达：聚（ADP-核糖）聚合酶1（PARP-1）、拓扑异构酶2A（TOPO-2A）、血管内皮生长因子（VEGF）、C-MYC、碱性成纤维细胞生长因子（bFGF）、基质金属蛋白酶（MMP-2和MMP-9）、人表皮生长因子1（HER1）和多药耐药（MDR）基因。
在TNBC组中，与非TNBC组相比，PARP-1、TOPO-2A、HER1、C-MYC、VEGF、bFGF和MMP-2的表达显著增加。
本研究结果表明：（1）TNBC患者将从TOPO-2A抑制剂以及抗血管生成和抗转移治疗中获益更多；（2）抑制这些靶基因正在成为治疗TNBC最令人兴奋和有前景的靶向治疗策略之一，其中预期靶点是DNA修复、肿瘤血管生成和转移。
