Breast cancer is a heterogeneous disease encompassing many subtypes, which differ both in terms of their molecular backgrounds and clinical prognosis. These breast cancer subtypes range from pre-invasive early stage disease to advanced invasive disease. The simplest classifications of disease subdivide breast cancer into pre-invasive and invasive forms; with the pre-invasive forms being ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Carcinoma in situ is proliferation of cancer cells within the epithelial tissue without invasion of the surrounding stromal tissue (Bland & Copeland, 1998). DCIS arises in the terminal ductal lobular units (TDLU) and in extra-lobular ducts while LCIS occurs in the breast lobules, and is recognisable histopathologically by the presence of populations of aberrant cells with small nuclei (Hanby & Hughes, 2008). Invasive breast cancers are subclassified into invasive ductal breast cancer, invasive lobular breast cancer, inflammatory breast cancer and Paget's disease. Invasive ductal carcinoma (IDC) is the most common formof invasive breast cancer, accounting for around 85% of all cases.

DCIS is frequently considered as an obligate precursor to IDC, progressing from lower to higher grades and then onto invasive cancer with progressive accumulation of genomic changes (Farabegoli et al ., 2002). However it has alternately been suggested that there exist genetically-distinct subgroups of DCIS, only some of which have the potential to progress to invasion (Shackney & Silverman, 2003). Long-term natural history studies of DCIS have provided supportive evidence for both possibilities (Page et al., 1995; Collins et al ., 2005; Sanders et al ., 2005). Despite such controversies, the large extent to which the genome is altered in DCIS strongly suggests that genomic instability precedes phenotypic evidence of invasion (Hwang et al ., 2004). This serves to underline the fact that malignant transformation in a heterogeneous disease like breast cancer is a dynamic process evolving through multiple multi-step pathway models.

Many factors are thought to be responsible for the development of breast cancer. Genetic factors play a vital role in the predisposition to breast cancer, with mutations of BRCA1 and BRCA2 genes accounting for 5–10% of breast cancer cases and being responsible for 80% of inherited breast cancers (Nathanson et al., 2001). On a more complex level, much insight has been gained from the genetic profiling of thousands of tumours to generate gene signatures of prognostic value (Sorlie et al., 2001; van 't Veer et al., 2002; van de Vijver et al ., 2002), which have spurred the development of commercially-available diagnostic tests. The importance of reproductive factors in the aetiology of breast cancer is also well recognised with early onset of menarche, nulliparity, late menopause, endogenous and exogenous hormones representing the main risk factors (Reeves et al ., 2000; Key et al., 2001; Howell & Evans, 2011). Several other studies have reported anincreased risk of breast cancer with lack of physical activity (especially in pre menopausal women), as well as increasing age and obesity (Clarke et al ., 2006; Walker & Martin, 2007; Harrison et al., 2009; Rod et al., 2009; Awatef et al ., 2011). These risk factors accentuate the abnormal growth control of cells by increasing the circulating levels of oestrogen thereby promoting tumourigenesis within the breast microenvironment. A proper understandingof the breast cancer microenvironment is essential for understanding breast cancer, and will be explored in detail in the next sections.

Lipid rafts are sub-domains of the cell membrane enriched in cholesterol and glycosphingolipids (Le Moyec et al., 1992; Nohara et al., 1998). These microdomains cluster together proteins involved in the regulation of crucial cellular processes; many of which are altered in cancer cells (Pike, 2003; de Laurentiis et al., 2007). Furthermore, lipid rafts are readily modified by diet and nutrition (Schley et al., 2007; Yaqoob, 2009), and studies have shown that fatty acid supplementation sensitises human mammary tumour cells to the cytotoxic effects of anti-cancer agents in vitro and in vivo (Germain et al., 1998; Menendez et al., 2005; Colas et al., 2006). This chapter will focus on the potential regulatory functions of lipid rafts as a novel approach towards understanding mechanisms of cancer initiation, progression and cell migration, a key event preceding metastatic progression. Finally it will discuss the potential of lipid rafts as novel therapeutic targets in breast cancer.

METHODS: We retrospectively investigated the role of CA 15-3 in conjunction with other clinico-pathological variables as a predictor of response and time to disease recurrence following treatment in LABC. Pre and post primary chemotherapy serum concentrations of CA 15-3 together with other variables were reviewed and related to four outcomes following primary chemotherapy (clinical response, pathological response, time to recurrence and time to progression). Persistently elevated CA 15-3 after PC was considered as consecutively high levels above the cut off point during and after PC.

RESULTS: 73 patients were included in this study. Patients received PC (AC or AC-T regimen) for locally advanced breast cancer. 54 patients underwent surgery. The median follow up was 790 days. Patients with high concentrations of CA 15-3 before PC treatment had a poor clinical (p = 0.013) and pathological (p = 0.044) response. Together with Her-2/neu expression (p = 0.009) and tumour lympho-vascular space invasion (LVI) (p = 0.001), a persistently elevated CA 15-3 post PC (p = 0.007) was an independent predictive factor of recurrence following treatment in LABC.

CONCLUSION: Elevated CA 15-3 level is predictive of a poor response to chemotherapy. In addition, persistently elevated CA 15-3 levels post chemotherapy in conjunction with lympho-vascular invasion and HER2 status predict a reduced disease free survival following treatment in locally advanced breast cancer.

METHODS: The medical records of 495 patients who underwent LC between September 1999 and September 2003 were reviewed. Variables such as complications, operating time, conversion to open procedure, hospital stay, and analgesia requirements were compared.

RESULTS: Two hundred and eighty-three patients underwent three-port LC and 212 patients underwent four-port LC. In total, 163 (32.9%) patients were diagnosed with AC and 332 (67.1%) with CC by histology. There was no statistical difference between the three and four-port groups in terms of complications, conversion to open procedure (p = 0.6), and operating time (p = 0.4). Patients who underwent three-port LC required less opiate analgesia (pethidine) than those who underwent four-port LC (p = 0.0001). The hospital stay was found to be related to the amount of opiates consumed (p = 0.0001) and was significantly shorter in the three-port LC group (p = 0.005).

CONCLUSION: Three-port LC is a safe procedure for AC and CC in expert hands. The procedure offers considerable advantages over the traditional four-port technique in the reduction of analgesia requirements and length of hospital stay.