Department of Obstetrics and Gynecology, J. W. Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Breast Cancer Res Treat. 2011 Nov;130(2):409-20. doi: 10.1007/s10549-010-1333-x. Epub 2011 Jan 4.
The luminal B subtype represents a group of high proliferating estrogen receptor positive breast cancers which are associated with a poor prognosis. Genes exclusively expressed in this subtype should help to better understand these tumors. In a finding cohort of 171 breast cancers luminal B specific genes were identified displaying strong expression in highly proliferating Ki-67 positive/ER positive tumors but no expression either in Ki-67 negative/ER positive or in Ki-67 positive/ER negative samples. The clinical relevance of the scaffold protein NHERF1 identified by this strategy was assessed in a total of 3,030 breast cancers. NHERF1 expression was associated with the luminal B subtype both in the finding and validation cohort. A positive correlation of NHERF1 expression with tumor size (P < 0.001), grade (P < 0.001), and HER2 status (P = 0.033) was observed. NHERF1 expression was associated with a worse survival in ER positive breast cancer (P < 0.001) and retained its prognostic value in multivariate analysis. For ER positive samples with low NHERF1 expression a benefit of endocrine therapy was detected (P = 0.007). In contrast no differences in disease free survival were found for high NHERF1 expressing breast cancers which were either treated with endocrine therapy or no systemic therapy. Our data indicate that NHERF1 expressing breast cancers seem to have a greater risk to develop resistance to endocrine therapy. However, based on previous findings of NHERF1 functioning in PI3K signalling from basic research, these tumors might be appropriate candidates for a targeted therapy of the PI3K/Akt pathway.
腔 B 型代表了一组高增殖雌激素受体阳性乳腺癌，与预后不良相关。仅在该亚型中表达的基因应有助于更好地理解这些肿瘤。在一个包含 171 例乳腺癌的发现队列中，鉴定了腔 B 型特异性基因，这些基因在高增殖 Ki-67 阳性/ER 阳性肿瘤中强烈表达，但在 Ki-67 阴性/ER 阳性或 Ki-67 阳性/ER 阴性样本中均无表达。通过这种策略鉴定的支架蛋白 NHERF1 的临床相关性在总共 3030 例乳腺癌中进行了评估。在发现和验证队列中，NHERF1 的表达与腔 B 型均相关。NHERF1 表达与肿瘤大小（P < 0.001）、分级（P < 0.001）和 HER2 状态（P = 0.033）呈正相关。NHERF1 表达与 ER 阳性乳腺癌的生存不良相关（P < 0.001），并在多变量分析中保留其预后价值。对于 NHERF1 低表达的 ER 阳性样本，检测到内分泌治疗的益处（P = 0.007）。相反，对于接受内分泌治疗或无系统治疗的高 NHERF1 表达乳腺癌，无疾病无进展生存期的差异。我们的数据表明，NHERF1 表达的乳腺癌似乎有更大的风险对内分泌治疗产生耐药性。然而，基于基础研究中 NHERF1 在 PI3K 信号传导中的作用的先前发现，这些肿瘤可能是针对 PI3K/Akt 通路的靶向治疗的合适候选者。
