Breast cancer is the second most commonly diagnosed cancer in women in Australia and the worldwide leading cause of cancer-related death in the female population. The current therapeutic options for this disease are targeted therapy, chemotherapy, endocrine therapy and immunotherapy. Although treatment options have improved, metastatic disease remains largely incurable. For example, less than 30% of women with the triple-negative breast cancer (TNBC) subtype treated with chemotherapy will survive 5 years. These poor outcomes highlight the need for new personalised and therapeutic approaches to (1) reduce the reliance upon toxic chemotherapies and (2) appropriately identify candidates who will derive benefit from therapy. Herein, we have identified that the molecule ‘cell division cycle associated protein 3’ (CDCA3) may prove useful as a diagnostic to enhance therapy response.
Our analysis of over 300 breast cancer tissue biopsies by immunohistochemistry analysis indicated that CDCA3 is a strong prognostic marker in Ki67+ and TNBC cases of disease. CDCA3 staining correlated with markers of poor prognosis (nuclear grade, mitotic score, nuclear pleomorphism) and was associated with a poor prognosis. Indeed, we also identified that women with the most common form of disease, hormone receptor + HER2- breast cancer, and have CDCA3low tumours, have a significantly poorer prognosis and response to chemotherapy than women whose tumours are CDCA3high. Our laboratory models confirm these clinical findings, whereby CDCA3high tumours are more sensitive to chemotherapeutic agents such as anthracyclines. Here, we have identified that precise control of CDCA3 levels is required to maintain genomic integrity and this presents novel therapeutic opportunities for CDCA3low tumours.
Our findings demonstrate the diagnostic potential for CDCA3 to identify therapy responders and has identified novel therapeutic options for CDCA3low tumours. With further evaluation, we propose that our personalised approach might enhance quality of life and begin to reduce the therapeutic reliance upon chemotherapy.