The term 'locally advanced breast cancer' covers a range of clinical scenarios, and has the implications that surgical clearance and local control will be difficult or impossible, and long-term survival rates will be poor. Treatment selection is particularly important in this group of patients to try to obtain maximum control of disease, and potentially improve surgical options and cure rates. Currently, assessment of estrogen receptor, progesterone receptor and human epidermal receptor 2 status in tumour samples remains the gold standard for prediction of response to endocrine therapy, chemotherapy or targeted agents such as trastuzumab. Progress has been made in identifying markers that can help select treatments likely to be associated with response and avoid those associated with resistance. These potential markers include Ki67 proliferation rate, cytochrome P450 (CYP) 2D6 expression, BRCA1/2 gene status and others.