Breast cancer is a dangerous disease that results in high mortality rates for cancer patients. Many methods have been developed for the treatment and prevention of this disease. Determining the expression patterns of certain target genes in specific subtypes of breast cancer is important for developing new therapies for breast cancer. In the present study, we performed a holistic approach to screening the mRNA expression of six members of the cell division cycle-associated gene family (CDCA) with a focus on breast cancer using the Oncomine and The Cancer Cell Line Encyclopedia (CCLE) databases. Furthermore, Gene Expression-Based Outcome for Breast Cancer Online (GOBO) was also used to deeply mine the expression of each CDCA gene in clinical breast cancer tissue and breast cancer cell lines. Finally, the mRNA expression of the CDCA genes as related to breast cancer patient survival were analyzed using a Kaplan-Meier plot. CDCA3, CDCA5, and CDCA8 mRNA expression levels were significantly higher than the control sample in both clinical tumor sample and cancer cell lines. These highly expressed genes in the tumors of breast cancer patients dramatically reduced patient survival. The interaction network of CDCA3, CDCA5, and CDCA8 with their co-expressed genes also revealed that CDCA3 expression was highly correlated with cell cycle related genes such as CCNB2, CDC20, CDKN3, and CCNB1. CDCA5 expression was correlated with BUB1 and TRIP13, while CDCA8 expression was correlated with BUB1 and CCNB1. Altogether, these findings suggested CDCA3, CDCA5, and CDCA8 could have a high potency as targeted breast cancer therapies.