Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea.
Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea.
J Breast Cancer. 2014 Mar;17(1):47-53. doi: 10.4048/jbc.2014.17.1.47. Epub 2014 Mar 28.
The effect of cyclin D1 overexpression on breast cancer outcomes and prognosis is controversial, even though amplification of the cyclin D1 gene, CCND1, has been shown to be associated with early relapse and poor prognosis. In this study, we examined the relationship between cyclin D1 overexpression and disease-specific survival (DSS). We also analyzed survival in patients who experienced recurrence.
We retrospectively analyzed data from patients diagnosed with ductal carcinoma between April 2005 and December 2010. We examined clinicopathologic factors associated with cyclin D1 overexpression and analyzed the influence of cyclin D1 on recurrence-free survival and DSS.
We identified 236 patients diagnosed with primary breast cancer who completed all phases of their primary treatment. Cyclin D1 overexpression was significantly associated with longer DSS (5-year DSS, 89.9% in patients without cyclin D1 overexpression vs. 98.9% in patients with cyclin D1 overexpression; p=0.008). Multivariate analysis also found that patients with cyclin D1 overexpressing tumors had significantly longer disease-specific survival than patients whose tumors did not overexpress cyclin D1, with a hazard ratio for disease-specific mortality of 7.97 (1.17-54.22, p=0.034). However, in the group of patients who experienced recurrence, cyclin D1 overexpression was not significantly associated with recurrence-free survival. Cyclin D1 overexpression was significantly associated with increased survival after disease recurrence, indicating that cyclin D1 overexpression might be indicative of more indolent disease progression after metastasis.
Cyclin D1 overexpression is associated with longer DSS, but not recurrence-free survival, in patients with breast cancer. Longer postrecurrence survival could explain the apparent inconsistency between DSS and recurrence-free survival. Patients with cyclin D1-overexpressing tumors survive longer, but with metastatic disease after recurrence. This information should spark the urgent development of tailored therapies to cure these patients.
尽管已经表明 cyclin D1 基因（CCND1）的扩增与早期复发和预后不良有关，但 cyclin D1 过表达对乳腺癌结局和预后的影响仍存在争议。在这项研究中，我们研究了 cyclin D1 过表达与疾病特异性生存（DSS）之间的关系。我们还分析了经历复发的患者的生存情况。
我们回顾性分析了 2005 年 4 月至 2010 年 12 月期间诊断为导管癌的患者的数据。我们检查了与 cyclin D1 过表达相关的临床病理因素，并分析了 cyclin D1 对无复发生存和 DSS 的影响。
我们确定了 236 例完成所有初始治疗阶段的原发性乳腺癌患者。cyclin D1 过表达与较长的 DSS 显著相关（无 cyclin D1 过表达的患者 5 年 DSS 为 89.9%，而 cyclin D1 过表达的患者为 98.9%；p=0.008）。多变量分析还发现，cyclin D1 阳性肿瘤患者的疾病特异性生存显著长于 cyclin D1 阴性肿瘤患者，疾病特异性死亡率的风险比为 7.97（1.17-54.22，p=0.034）。然而，在经历复发的患者中，cyclin D1 过表达与无复发生存无显著相关性。cyclin D1 过表达与复发后生存时间延长显著相关，表明 cyclin D1 过表达可能提示转移后疾病进展更为惰性。
在乳腺癌患者中，cyclin D1 过表达与较长的 DSS 相关，但与无复发生存无关。复发后的生存时间延长可能解释了 DSS 与无复发生存之间的明显不一致。cyclin D1 过表达肿瘤患者的生存期较长，但在复发后仍患有转移性疾病。这一信息应该引发对制定针对这些患者的个体化治疗方案的迫切需求。
