Cyclin A2 and Ki-67 proliferation markers could be used to identify tumors with poor prognosis in African American women with breast cancer.

Abstract

Background: Diagnosed invasive breast carcinomas in African American patients are more aggressive compared with those in Caucasian patients and diagnosed at later stages of the disease with higher grade tumors. Despite advances in breast cancer systemic treatment, new prognostic and predictive biomarkers are still needed. Therefore, potential biomarkers were chosen to correlate with different subtypes, recurrence, and survival of invasive breast cancer in a cohort of African American women.

Methods: Eight protein biomarkers (ER, PR, HER2, Cyclin A2, Cytokeratin 5, Vimentin, Bcl2, and Ki-67) were evaluated using tissue microarrays (TMAs) and immunohistochemistry (IHC). The IHC results from TMAs were analyzed by both supervised and unsupervised clustering methods. The predictive clusters for the supervised and unsupervised methods were compared for agreement with the empirical classification. Kappa values were used to determine the overall percent correct clusters and agreement between specific clusters. Chi-square statistics was used to examine the association between hierarchical and multinomial logistic clustering methods.

Results: Five subtypes of breast tumors with distinct protein expression patterns were identified among the studied 166 breast tumors. Luminal B tumors have been distinguished from luminal A tumors by staining for cell cycle proteins Cyclin A2 and Ki-67, which promote cell proliferation. Forty-nine percent were stained positive for Cyclin A2, 39.2% positive for Ki-67, and 37% positive for both Cyclin A2 and Ki-67. The age of patients did not show any significant effect whether five (p-value= 0.576) or eight (p-value= 0.605) biomarkers were used, which indicating that age did not have any influence on the classification of the subtypes. Ninety percent of the thirty triple negative tumors were positive for Cyclin A2 or Ki-67 or both. Six-year overall survival was better for luminal A tumors (76%) than luminal B tumors (71%). Likewise, six-year relapse-free survival was better for luminal A tumors (76%) than luminal B tumors (29%).

Conclusion: Discovery of molecular markers such as Cyclin A2 and Ki-67, and subtypes that are most prevalent in African Americans could lead to a better understanding of the factors contributing to higher morbidity and mortality in this group and to aid in decision-making to offer earlier treatment.