[Trastuzumab in early breast cancer]

Abstract

Background: The HER2 gene or c-erb B2 or neu is amplified in 15-25% of breast cancers. This amplification is associated with an aggressive course of disease. The trastuzumab is a monoclonal antibody targeting the extracellular domain of HER2. This is the first targeted molecule designed to treat breast cancer. In the firstline metastatic disease, trastuzumab in combination with chemotherapy significantly improved survival of patients with HER2-positive disease. In the adjuvant setting, trastuzumab has been evaluated in several randomized trials.

Objective: The purpose of this literature review is to evaluate the efficacy and safety of Trastuzumab in the adjuvant treatment of HER2-positive breast cancer.

Methods: A search of articles published in English literature, between 1987 (date of establishment of prognostic value of HER2) and November 2012, was conducted on Medline and in the database of the main international congress using the following terms: "breast cancer", "HER2-positive", "adjuvant therapy" and "Trastuzumab".

Results: We identified seven randomized phase 3 trial evaluating trastuzumab in the adjuvant treatment of HER2-positive. The trastuzumab was administered weekly or every 3weeks. Its administration with concomitant taxane chemotherapy and with concurrent radiotherapy was preferred. Four randomized trials have clearly confirmed the benefit of trastuzumab, two positive in overall survival (OS) and progression free survival (PFS), and two positive in PFS. The duration of trastuzumab for 1year was the most effective. The trastuzumab was well tolerated. The most significant toxicity, associated with trastuzumab, was cardiac toxicity. However, it is found in only 5% or less of cases, and it is severe in only 2% or less of cases, and most patients recovered their cardiac function by medical treatment alone.

Conclusion: In the contemporary medical literature, several strong arguments confirm the benefit in survival of trastuzumab administered concomitantly with a taxane-based chemotherapy and with concurrent radiotherapy, and for a period of 1year. Trastuzumab was well tolerated. Only 2% or less of patients experienced a serious cardiac toxicity, but it was reversible in most of the time.