The Predictive Value of HER2 in Breast Cancer

Measurement of molecular markers predictive of response to therapy should enable more selective and effective utilization of anticancer agents. The predictive value of HER2 remains a complex and inconclusive subject. In metastatic breast cancer, HER2-positive, ER-positive patients can show responses to endocrine treatment, but experience shorter time to progression and survival than HER2-negative patients. In the adjuvant setting, weak, retrospective evidence suggests that tamoxifen is potentially harmful in HER2-positive patients and that there is no benefit from prolonged tamoxifen therapy. It has not yet been demonstrated conclusively that HER2 positivity increases resistance to adjuvant cyclophosphamide, methotrexate, 5-FU (CMF), but there are indications that HER2-positive patients benefit more from adequately dosed anthracyclines than from CMF. The greatest value of HER2 as a predictive marker lies in the prediction of response to therapies that target HER2, such as Herceptin. Patients with strongly HER2-positive breast cancer derive significant clinical benefit from single-agent and combined Herceptin therapy. HER2 testing has become an integral part of the optimal management of the breast cancer patient. Best current practice in adjuvant breast cancer therapy based on the current knowledge of the potential predictive power of HER2 constitutes not denying tamoxifen to HER2-positive, ER-positive patients or CMF to HER2-positive patients. Outside of clinical trials, adequately dosed anthracycline-based chemotherapy is the current preferred adjuvant treatment option for HER2-positive patients.