Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future?

Abstract

Prognosticators evaluating survival in breast cancer vary in significance in respect to lymph node status. Studies have shown e.g. that HER2/neu immunohistochemistry or HER2/neu gene amplification analysis do perform well as prognosticators in lymph node positive (LN +) patients but are less valuable in lymph node negative (LN -) patients. We collected data from different studies and tried to evaluate the relative significance of different prognosticators in LN+/LNpatient groups. In LN+ patients HER2/neu and E-cadherin immunohistochemistry were the statistically most significant prognosticators followed by proliferation associated features (mitotic counts by SMI (standardised mitotic index) or MAI (mitotic activity index), or S-phase fraction). Bcl-2 immunohistochemistry was also significant but p53 and cystatin A had no significance as prognosticators. In LN-patients proliferation associated prognosticators (SMI, MAI, Ki-67 index, PCNA immunohistochemistry, S-phase fraction) are especially valuable and also Cathepsin D, cystatin A, and p53 are significant, but HER2/neu or bcl-2, or E-cadherin less significant or without significance. We find that in studies evaluating single prognosticators one should distinguish between prognosticators suitable for LN+ and LN-patients. This will allow the choice of best prognosticators in evaluating the prospects of the patient. The distinction between LN+ and LNpatients in this respect may also be of special value in therapeutic decisions.

Proliferative Activity in Libyan Breast Cancer with Comparison to European and Central African Patients

“…LN+ and LN− patients had different prognosticators, and proliferative indices seem to be strong in LN+ patients. The data in Elzagheid et al [5] was on Caucasians, but also in our study there were no deaths in LN− patients (Table 5). …”

“…Mitotic count is the best prognosticator of survival in breast cancer in Caucasian human population, particularly in lymph node-negative patients [1–5]. There is evidence that this might also be true of African breast cancer [6].…”

Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer

“…It is a circulating peptide hormone and locally acting growth factor with both paracrine and autocrine functions (Elzagheid et al 2006;Lu et al 2006). IGF2 gene is localized at chromosome 11p15.5 and is flanked by the insulin and H19 genes in a region that is known to have differential parental methylation.…”

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

“…ER-positive/PR-negative tumors express higher levels of HER-1 and, especially, HER-2 and have more aggressive features than ER/PRpositive tumors [12,16]. Overexpression of receptors for growth factors such as HER-2 has also been shown to play an important prognostic role, independent of lymph node status, tumor size, or ER-status [17][18][19][20][21].…”