Abstract
BackgroundBreast cancer is the most common cancer in women in the U.S. and Western Europe. Amplification of the her-2/neu gene occurs in approximately 25% of invasive ductal carcinomas of the breast. The first HER-2/neu-targeted approach to reach the clinic was trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER-2/neu protein. Trastuzumab therapy prolongs the survival of patients with metastático HER-2/neu-overexpressing breast cancer when combined with chemotherapy and has recently been demonstrated to lead to dramatic improvements in disease-free survival when used in the adjuvant therapy setting in combination with or following chemotherapy. Here, we performed a meta-analysis of completed clinical trials of adjuvant trastuzumab in the adjuvant setting. Survival, recurrence, brain metastases, cardiotoxicity and directions for future research are discussed.MethodsA meta-analysis of randomized controlled trials (RCT) was performed comparing adjuvant trastuzumab treatment for HER2-positive early breast cancer (EBC) to observation. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings were systematically searched for evidence. Relevant reports were reviewed by two reviewers independently and the references from these reports were searched for additional trials, using guidelines set by QUOROM statement criteria.ResultsPooled results from that five randomized trials of adjuvant Trastuzumab showed a significant reduction of mortality (p < 0.00001), recurrence (p < 0.00001), metastases rates (p < 0.00001) and second tumors other than breast cancer (p = 0.007) as compared to no adjuvant Trastuzumab patients. There were more grade III or IV cardiac toxicity after trastuzumab (203/4555 = 4.5%) versus no trastuzumab (86/4562 = 1.8%). The likelihood of cardiac toxicity was 2.45-fold higher (95% CI 1.89 – 3.16) in trastuzumab arms, however that result was associated with heterogeneity. The likelihood of brain metastases was 1.82-fold higher (95% CI 1.16 – 2.85) in patients who received trastuzumab.ConclusionThe results from this meta-analysis are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk: benefit ratio demonstrated in these studies. Adequate assessment of HER-2/neu status is critical, and careful cardiac monitoring is warranted because of cardiac toxicity. Clinical trials should be designed to answer unsolved questions.
Highlights
Breast cancer is the most common cancer in women in the U.S and Western Europe
Hoffmann-La Roche Ltd., Basel, Switzerland), a monoclonal antibody directed against HER-2, improves survival and quality of life when given in combination with taxanes as first-line therapy in women with metastatic breast cancer [3,4,5] and has shown efficacy as monotherapy [6,7]
This study evaluated the efficacy and safety of three regimens as adjuvant systemic therapy after surgery: (1) doxorubicin and cyclophosphamide followed by trastuzumab plus docetaxel chemotherapy (AC.TH), (2) docetaxel and carboplatin plus trastuzumab (TCH), and (3) AC followed by docetaxel alone (AC.T) as the control arm
Summary
Breast cancer is the most common cancer in women in the U.S and Western Europe. Amplification of the her-2/neu gene occurs in approximately 25% of invasive ductal carcinomas of the breast. We have the results of five large appropriately powered studies assessing the role of trastuzumab in addition to adjuvant chemotherapy for patients with HER2 positive tumours [5,6,7] In this way, our group investigated whether the administration of trastuzumab was effective as adjuvant treatment for HER2positive breast cancer if used after completion of the primary treatment for reducer mortality, recurrence, metastases and subsequent other tumors than breast cancer rate. Our group investigated whether the administration of trastuzumab was effective as adjuvant treatment for HER2positive breast cancer if used after completion of the primary treatment for reducer mortality, recurrence, metastases and subsequent other tumors than breast cancer rate The another objective the current review was to evaluate the incidence of cardiac toxicity and brain metastases to give a more balanced view of the total evidence and to increase statistical precision
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call