HER2 as a Prognostic Factor in Breast Cancer

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.