Breast cancer

The notion that breast cancer is not a single disease but many – that there is considerable heterogeneity among different tumors – is not new, having been observed by physicians for decades. But with the advent of powerful analytical and computational tools, systems biology has provided a fascinating view of the underlying mutations, biology, and networks that drive the process of breast tumorigenesis. The information derived from analyzing these networks is also proving to be clinically useful and is beginning to be incorporated into the standard clinical management of breast cancer patients – to determine prognosis and guide the choice of therapeutics, for example. However, these advances are complicated by the heterogeneity of cancer cell phenotypes that exist within a single tumor, which drives metastasis, resistance to treatment, and, eventually, recurrence. Systems biology offers a strong tool for investigating both levels of heterogeneity to comprehensively define, and ultimately attack, the aberrant molecular networks governing breast cancer cells. Epidemiology Breast cancer is a staggering public health problem. The American Cancer Society expects that over 232,000 cases of invasive breast cancer will be diagnosed in 2014, accounting for the largest number of cancer cases in women (ACS, 2014). Nearly 40,000 deaths are predicted to occur, which rank it the second leading cause of cancer deaths in women, behind only lung cancer. Fortunately, the number of newly diagnosed cases has decreased since 2000, largely as a result of a reduction in number of post-menopausal women on hormone replacement therapy, which has been strongly linked to the development of breast cancer (Rossouw et al., 2002). Death rates have also decreased in recent years and this has been attributed to improvements in screening and early detection with mammography as well as better treatment options (ACS, 2012). However, racial disparities do exist as African American women have a lower incidence rate but an increased chance of death (ACS, 2011). While this may reflect socioeconomic factors and access to health care, there also seems to be a biological difference since African American women are more likely to be diagnosed with aggressive cancers (Amend et al., 2006; Stead et al., 2009). Additionally, over 62,000 cases of carcinoma in situ are expected in 2014 (ACS, 2014). These are non-invasive neoplasms and likely represent a pre-malignant stage in the progression toward invasive breast cancer (Burstein et al., 2004).