J Breast Cancer.  2014 Mar;17(1):47-53.

Longer Survival in Patients with Breast Cancer with Cyclin D1 Over-Expression after Tumor Recurrence: Longer, but Occupied with Disease

• Chung J
• Noh H
• Park KH
• Choi E
• Han A

Abstract

PURPOSE
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.

Keyword

Breast neoplasms; Cyclin D1; Disease-specific survival; Recurrence

MeSH Terms

Breast Neoplasms*
Breast*
Carcinoma, Ductal
Cyclin D1*
Cyclins*
Disease Progression
Genes, bcl-1
Humans
Mortality
Multivariate Analysis
Neoplasm Metastasis
Prognosis
Recurrence*
Retrospective Studies
Cyclin D1
Cyclins

Figure

• 

  Figure 1 Microphotographs showing cyclin D1 positive and negative tumors. (A) Cyclin D1 positive breast cancer with histologic grade 1 (H&E stain, ×40) and (B) same tumor with immunohistochemical staining of cyclin D1 and it showed more than 60% tumor cells were cyclin D1 positive (immunohistochemical stain for cyclin D1, ×400). (C) Cyclin D1 negative breast cancer with histologic grade 3 (H&E stain, ×40) and (D) same tumor with immunohistochemical staining showed no cyclin D1 positive cells (immunohistochemical stain for cyclin D1, ×400).

• 

  Figure 2 Kaplan-Meier curves for disease specific survival stratified by cyclin D1 overexpresson. Kaplan-Meier survival curve for patients with (solid line) or without (dotted line) cyclin D1 overexpression showed statistically significant different overall survival (p=0.008).

• 

  Figure 3 Median survival time (MST) of recurrence free survival and survival after recurrence by cyclin D1 overexpression in patients with experienced recurrence. Cyclin D1 overexpression was not correlated with a difference in recurrence free survival (p=0.269) but significantly associated with increased survival after disease recurrence (p=0.012). RFS=recurrence free survival.

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