Mitochondrial ATP synthase and associated bioenergetic proteins: can expression predict response to chemotherapy in locally advanced breast cancer?

[Truncated abstract] Breast Cancer is the leading cause of cancer death amongst Australian women. Cytotoxic chemotherapy has a demonstrated utility in treating breast cancer and has contributed to an increase in survival at the population level. On an individual level however, there are some people who respond to therapy and others that do not. Despite significant advances in our understanding of breast biology there are still substantial gaps in our knowledge to as to why not all patients respond in the same way to chemotherapy. There exists no current means of identifying which patients will respond to therapy and which patients will not. To address this there is substantial interest in investigating the complex molecular characteristics of tumours and how these underlie and influence tumour biology and behaviour in the hope these might provide further predictive and prognostic information. Indeed, there is a global focus amongst breast cancer researchers to use a molecular understanding of breast cancer as a means to develop predictors of response to therapy so that a more individualised approach to breast cancer treatment can be delivered. The ability to do this will have an inevitable consequence of improved outcomes in terms of patient survival and quality of life. The use of neoadjuvant chemotherapy treatment in the management of locally advanced breast cancer (LABC) provides a convenient platform for biological studies that examine potential pathological and molecular markers of response to therapy in vivo. The assessment of response at the completion of chemotherapy provides a practical endpoint which can be reached in approximately six months, depending on the chemotherapy regime. This enables the study of markers that predict a response to therapy to be identified in a relatively short time frame, and contrasts with the years of follow-up required to obtain survival information and identify markers indicative of prognosis. One way in which cytotoxi