Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer

Abstract

Evidence is accumulating that breast cancer is not one disease but many separate diseases. DNA microarray-based gene expression profiling has demonstrated subtypes with distinct phenotypic features and clinical responses. Prominent among the new subtypes is 'basal-like' breast cancer, one of the 'intrinsic' subtypes defined by negativity for the estrogen, progesterone, and HER2/neu receptors and positivity for cytokeratins-5/6. Focusing on basal-like breast cancer, we discuss how molecular technologies provide new chemotherapy targets, optimising treatment whilst sparing patients from unnecessary toxicity. Clinical trials are needed that incorporate long-term follow-up of patients with well-characterised tumour markers. Whilst the absence of an obvious dominant oncogene driving basal-like breast cancer and the lack of specific therapeutic agents are serious stumbling blocks, this review will highlight several promising therapeutic candidates currently under evaluation. Thus, new molecular technologies should provide a fundamental foundation for better understanding breast and other cancers which may be exploited to save lives. (Part of a Multi-author Review).

Semi-automated evaluation of Ki-67 index in invasive ductal carcinoma of the breast

“…Early breast cancer has a highly variable prognosis and the benefit of existing therapies is often unpredictable. Several morphological parameters, including tumor size, histological grade, vascular invasion and lymph node metastasis, are useful in this regard, but insufficient (8). This has lead to the study of tumor molecular characteristics and currently ER, PR and HER2 are recognized as prognostic and predictive factors (10,12).…”

“…The reaction to HER2 was scored as follows: 0 (negative), absent or present in <10% of tumor cells; 1+ (negative), membranous, weak and discontinuous in >10% of tumor cells; 2+ (questionable), membranous, low/moderate and continuous in >10% of tumor cells or membranous, intense and continuous in ≤30% of tumor cells; and 3+ (positive), membranous, intense and continuous in >30% of tumor cells. Cases were stratified as luminal breast carcinoma (ER + and/or PR + / ± HER2 + ) and non-luminal breast carcinoma (represented by all ER- and PR-negative cases) (5,7,8,24). …”

“…Based on gene expression in the tumor cells of breast carcinomas, Perou et al (5) successfully identified several tumor subtypes with specific properties with regard to epidemiology, natural evolution and response to systemic and local adjuvant therapy. Immunohistochemistry (IHC) was used as a surrogate method for molecular subtyping, based on estrogen receptors (ERs), progesterone receptors (PRs), EGFR, HER2 and cytokeratin-5 expression (6–8). Additional studies have shown the necessity of refining criteria for IHC characterization of these tumor subtypes.…”

Histological types of breast cancer: How special are they?

“…This should not come as a surprise, given that BRCA1 has been shown to play a pivotal role in the regulation of ER expression and that RNA interference-mediated silencing of BRCA1 in breast cancer cell lines leads to a marked reduction in expression of endogenous levels of ER (Hosey et al, 2007) and in increased expression of markers usually found in basal/myoepithelial cells (e.g. cytokeratins 5 and 17, and P-cadherin) (Gorski et al, 2009;Mullan, 2006).…”

Opportunities for PET to deliver clinical benefit in cancer: breast cancer as a paradigm

“…The developments of tumour subtyping and the availability of a broader range of treatments [ 4 ] are likely to lead to changes in how patients with breast cancer are managed clinically, as summarised in Fig. 1.…”