HER2 as a Prognostic Factor in Breast Cancer

Abstract

HER2 amplification/overexpression is a marker of poor prognosis in breast cancer. The prognostic impact of HER2 positivity is lower in node-negative compared with node-positive women. The only significant, independent prognostic factors in breast cancer are node status, HER2 status and menopausal status. HER2-positive tumors also contain p53 abnormalities, tend to be hormone receptor and bcl-2 negative, have lymphoid infiltration (LI) and a high mitotic index. Patients with LI who are HER2 positive have a better prognosis than those who are HER2 negative, whereas HER2-positive patients without LI have a significantly worse prognosis than HER2-negative patients. Morphological and biological alterations appear to identify two categories of breast tumor. Two hypotheses may explain the progression to two tumor types: (1) atypical ductal hyperplasia (ADH) is a precursor of ductal carcinoma in situ (DCIS), which is a precursor of invasive ductal carcinoma (IDC); or (2) ADH is a precursor of HER2-negative IDC whereas DCIS is a precursor of HER2-positive IDC. The second theory fits well with two breast cancer subsets and the characteristics of ADH and DCIS. The first type of IDC occurs in older patients, progresses slowly due to estrogen dependency but is aggressive long term. The other type progresses rapidly, is HER2 positive and is more likely to occur in young patients.

A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer

“…Despite the total lack of methodologic standardization, the prevalence of HER-2-positive tumors is reasonably constant among studies, ranging from 19% to 35% (Table 2). This is in line with the reported proportion of HER-2-positive tumors in different settings (29).…”

Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer

“…It is involved in normal breast growth and development, and overexpression of HER2 seems to play a role in malignant transformation and tumourigenesis. HER2 was first reported in preinvasive breast cancer, and higher expression in DCIS than in IDC has been demonstrated (Ross and Fletcher, 1998;Menard et al, 2001). The explanation of this phenomenon was, that HER2-negative IDCs might not derive from DCIS, but develop from another lesion, the atypical ductal hyperplasia (ADH), which showed no HER2 amplification (Menard et al, 2001).…”

“…HER2 was first reported in preinvasive breast cancer, and higher expression in DCIS than in IDC has been demonstrated (Ross and Fletcher, 1998;Menard et al, 2001). The explanation of this phenomenon was, that HER2-negative IDCs might not derive from DCIS, but develop from another lesion, the atypical ductal hyperplasia (ADH), which showed no HER2 amplification (Menard et al, 2001). The same might be the case in PRL-3 expression, but to date, there is no data on the expression of PRL-3 in ADH.…”

Biologic and therapeutic role of HER2 in cancer

“…Various clinical studies have evaluated the relationship between HER2 and breast cancer outcome, and most have shown that women with HER2-positive tumors have a poorer prognosis than women with HER2-negative tumors (Me´nard et al, 2000(Me´nard et al, , 2001bMasood and Bui, 2002). However, while the prognostic value of HER2 amplification/overexpression in node-positive patients has been widely demonstrated, there is no consensus on its value in node-negative cases (Press et al, 1997;Ross et al, 1998;Volpi et al, 2000;Cooke et al, 2001).…”