HER2 and ER Status as Prognostic Indicators

The degree of pathologic response of tumor to primary chemotherapy is of considerable prognostic importance in patients with breast cancer. The addition of docetaxel (Taxotere) to an anthracycline-based primary chemotherapy regimen has been shown to result in significantly improved pathologic breast cancer response. The identification of predictors of treatment response will permit cytotoxic regimens to be tailored to individual patient requirements and permit pathologic response rates to be improved.

Estrogen-receptor (ER) status and tumor grade are known prognostic factors for survival, although their ability to predict the response of breast cancers to chemotherapy is uncertain. Expression of the oncogene HER2 has been shown to predict susceptibility to doxorubicin and resistance to cyclophosphamide (Cytoxan, Neosar). However, the predictive value of HER2 expression in patients who receive docetaxel is unknown.

The aim of this study was to identify any relationship between ER status, tumor grade, HER2 expression, and a substantial pathologic response in patients with breast cancer following treatment with docetaxel.

Histopathologic parameters were studied on core biopsies taken from 101 patients with breast cancer prior to receiving primary docetaxel. Tumors were typed and graded. Immunohistochemistry was carried out using a standard three-stage avidin biotin peroxidase complex technique. Antigen retrieval employed microwave technology. Specific monoclonal antibodies (with appropriate controls) were used to detect estrogen receptors and HER2 oncoprotein. Pathologic response was determined from operative specimens.

Univariate and multivariate analysis (UA and MVA) (logistic regression) were used to assess the predictive power of each variable. Univariate analysis revealed that ER negativity (P < .001) but not HER2 positivity (P = .289) distinguished patients with a substantial pathologic response. Multivariate analysis suggested that only ER negativity (P = .010) independently predicted a substantial response. High tumor grade, tumor type, and node status did not predict a good response on UA or MVA.

CONCLUSION: Breast cancers that are estrogen-receptor negative are more likely to achieve a near-complete or complete pathologic response to primary docetaxel.

Click here for Dr. Gabriel N. Hortobagyi’s commentary on this abstract.