Trastuzumab: Molecularly targeted therapy for early and metastatic HER-2/neu-positive breast cancer

PURPOSE: To review recent clinical trials that have evaluated the safely and efficacy of trastuzumab in the treatment of early and metastatic breast cancer overexpressing HER-2/neu EPIDEMIOLOGY: Breast cancer affects more than 200 000 women in the United States each year, and accounts for an estimated 40 000 deaths annually. It is not a single entity, but a clinically diverse group of malignancies with varying natural histories and responses to therapy. Overexpression of the proto-oncogene HER-2/neu defines a unique subset of breast cancers, is seen in 20% to 30% of breast tumors overall, and is associated with more aggressive disease and reduced survival time in node-positive and node-negative patients. REVIEW SUMMARY: HER-2/neu is an attractive therapeutic target, particularly because its overexpression is essential for initiating and maintaining tumor growth and progression. Clinical trials have demonstrated that targeted therapy with the HER-2/neu-specific monoclonal antibody trastuzumab, either alone or in combination with other cytotoxic agents, can produce durable objective responses, and increase time to disease progression and survival time in women with metastatic tumors that overexpress HER-2/neu. More recent studies evaluating the drug with or following chemotherapy in women with early HER-2/neu-positive breast cancer have shown that it also has a marked clinical benefit in this population, decreasing the risk of relapse by approximately 50%. This represents the largest degree of therapeutic benefit in early breast cancer reported since the introduction of tamoxifen for hormone receptor-positive disease approximately 25 years ago. TYPE OF AVAILABLE EVIDENCE: Meta-analyses, randomized trials, retrospective cohort studies, unstructured reviews, and conference proceedings/presentation slides. GRADE OF AVAILABLE EVIDENCE: Good, CONCLUSION: Trastuzumab reflects real progress in the treatment of HER-2/neu-positive breast cancer and underscores the value of targeted therapy. Clinical trials have demonstrated that trastuzumab improves clinical outcomes and offers a survival benefit to patients with early or metastatic breast cancer overexpressing HER-2/neu. Careful patient selection for HER-2/neu overexpression is essential prior to therapy, as is frequent cardiac monitoring prior to and during therapy.