Abstract

Breast cancer is the most common form of cancer among women. In 2009, an estimated 194,280 new cases of breast cancer were diagnosed in the United States; breast cancer was estimated to account for 27% of all new cancer cases and 15% of cancer-related mortality in women (Jemal et al, 2009). Similarly, in Europe in 2008, the disease accounted for some 28% and 17% of new cancer cases and cancer-related mortality in women respectively (Ferlay et al, 2008). The increasing incidence of breast cancer worldwide will result in an increased social and economic burden; for this reason there is a pressing need from a health and economics perspective to develop and provide appropriate, patient specific treatment to reduce the morbidity and mortality of the disease. Understanding the aetiology, biology and pathology of breast cancer is hugely important in diagnosis, prognostication and selection of primary and adjuvant therapy. Breast tumour behaviour and outcome can vary considerably according to factors such as age of onset, clinical features, histological characteristics, stage of disease, degree of differentiation, genetic content and molecular aberrations. It is increasingly recognised that breast cancer is not a single disease but a continuum of several biologically distinct diseases that differ in their prognosis and response to therapy (Marchionni et al, 2008; Sorlie et al, 2001). The past twenty years has seen significant advances in breast cancer management. Targeted therapies such as hormonal therapy for estrogen receptor (ER) positive breast tumours and trastuzumab for inhibition of HER2/neu signalling have become an important component of adjuvant therapy and contributed to improved outcomes (Fisher et al, 2004; Goldhirsch et al, 2007; Smith et al, 2007). However, our understanding of the molecular basis underlying breast cancer heterogeneity remains incomplete. It is likely that there are significant differences between breast cancers that reach far beyond the presence or absence of ER or HER2/neu amplification. Patients with similar morphology and molecular phenotype based on ER, PR and HER2/neu receptor status can have different clinical courses and responses to therapy. There are small ER positive tumours that behave aggressively while some large high grade ER negative, HER2/neu receptor positive tumours have an indolent course. ER-positive tumours are typically associated with better clinical outcomes and a good response to

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