Combined use of absolutely quantitated cyclin D1 and Ki67 protein levels to improve prognosis of Luminal-like breast cancer

Purpose: Both Ki67 and cyclin D1 are routinely used protein biomarkers of cell proliferation for breast cancer patients. Ki67 is used to differentiate Luminal A-like from Luminal-B like subtype in surrogate assay. These two proliferative factors are investigated in this retrospective study to evaluate their prognostic role on the overall survival (OS) of Luminal-like breast cancer patients. Method: The cyclin D1 protein level was measured absolutely and quantitatively using Quantitative Dot Blot (QDB) method in 143 Luminal-like FFPE breast cancer specimens. An optimized cutoff at 0.71 μmole/g was identified and used to separate these specimens into cyclin D1 high and low groups alone, or in combination with Ki67, for overall survival (OS) analyses of these patients. Results: Cyclin D1 was found to be an independent prognostic factor from Ki67 in univariate and multivariate analysis. When both biomarkers were used to separate these Luminal-like specimens, the group with low expression of both biomarkers (n=52) had significantly improved 10 year survival probability at 94%, while the one with high expression of both markers (n=34) were at 41% based on Kaplan-Meier survival analysis of OS (Log rank test p<0.0001). Conclusion: We demonstrated cyclin D1 as an independent prognostic protein biomarker from Ki67 for Luminal-like breast cancers. The combined usage of cyclin D1 and Ki67 significantly improved the prognosis over current prevailing surrogate assay. We propose to incorporate cyclin D1 in surrogate assay to improve prognosis for Luminal-like breast cancer patients in future clinical practice.