Trastuzumab‐based neoadjuvant therapy in patients with HER2‐positive breast cancer

Abstract

Overexpression, or gene amplification, of the human epidermal growth factor receptor 2 (HER2) is evident in 20% to 25% of breast cancers. The biologic agent trastuzumab is an HER2-targeted monoclonal antibody that inhibits the proliferation of tumor cells and induces tumor cell death through multiple mechanisms of action. Currently, trastuzumab is approved for use in the adjuvant and metastatic settings. Trials combining trastuzumab with neoadjuvant chemotherapy suggest that patients with HER2-positive breast cancer also may benefit from preoperative trastuzumab. For this article, the author reviewed efficacy and safety data from key studies of patients who received neoadjuvant trastuzumab-based therapy. Studies were identified from literature searches of publication and congress databases. The results of 3 large phase 3 trials (the M. D. Anderson Cancer Center neoadjuvant trastuzumab trial, the Neoadjuvant Herceptin [NOAH] trial, and the German Breast Group/Gynecologic Oncology Study Group ''GeparQuattro'' trial) demonstrated that, compared with chemotherapy alone, neoadjuvant trastuzumab plus chemotherapy significantly increased pathologic complete response rates to as high as 65%. Improvements in disease-free, overall, and event-free survival also were reported in the NOAH trial. In addition to demonstrated efficacy, a low incidence of cardiac dysfunction suggests that neoadjuvant trastuzumab is both effective and well tolerated. Similar results have been reported in a range of phase 2 studies using different trastuzumab-based regimens. These encouraging data led the National Comprehensive Cancer Network to recommend treating patients who have operable, locally advanced, HER2-positive breast cancer with neoadjuvant paclitaxel plus trastuzumab followed by 5-fluorouracil, epirubicin, and cyclophosphamide plus trastuzumab. Cancer 2010;116:2856-67. V C 2010 American Cancer Society.KEYWORDS: neoadjuvant, trastuzumab, HER-2, chemotherapy, biologic, breast cancer, breast conservation surgery, lymph node management.Breast cancer (BC) is the most frequently diagnosed form of cancer among women in the United States. 1 Of the various subtypes of BC, tumors that have gene amplification or protein overexpression of human epidermal growth factor receptor 2 (HER2) are among the most aggressive and are associated with poor clinical outcomes compared with tumors that do not have HER2 overexpression. 2-4 Of the total number of patients diagnosed with BC in the United States, 20% to 25% will have tumors that exhibit HER2 gene amplification or protein overexpression. 2,5,6 Trastuzumab (Herceptin), a humanized, monoclonal antibody that blocks the activity of HER2, is the only anti-HER2 agent that is approved for adjuvant therapy in patients who have HER2-positive disease with either positive or negative lymph node status, estrogen receptor (ER)/progesterone receptor (PR)-negative disease, or a high-risk feature, either in combination with chemotherapy or as a single agent after chemotherapy. Adjuvant trastuzumab significantly imp...

Systemic Targeted Therapy for her2-Positive Early Female Breast Cancer: A Systematic Review of the Evidence for the 2014 Cancer Care Ontario Systemic Therapy Guideline

“…Several systematic reviews of neoadjuvant trastuzumab have recently been published [17][18][19][20][21] . Most rcts (and thus reviews) reported pcr as the primary endpoint.…”

Reversible cardiotoxicity in a 54-year-old woman treated with trastuzumab

“…New diagnosis resources and more effective therapy schedules have contributed to increase the survival of patients with more aggressive breast cancer that over-expresses or amplifi es the HER2 gene [1][2][3][4] . Nevertheless, adverse effects of chemotherapy (CT) agents, including cardiotoxicity, have been more often observed and this can negatively affect both quality of life and outcome of patients from this group 1,3,5,6 .…”

“…Nevertheless, adverse effects of chemotherapy (CT) agents, including cardiotoxicity, have been more often observed and this can negatively affect both quality of life and outcome of patients from this group 1,3,5,6 . Trastuzumab (a monoclonal antibody targeting the HER2 gene) and paclitaxel (an antimicrotubule agent) have been employed with success to treat HER2 positive breast cancer [1][2][3]5 . The incidence of cardiac adverse events associated with isolated use of trastuzumab ranges from 2 to 4% 1,3,5,7 ; and may increase up to 16% with previous use of anthracycline and/or cyclophosphamide 1,[3][4][5][6][7] .…”

Development of^99mTc-radiolabeled nanosilica for targeted detection of HER2-positive breast cancer

“…2 The development of trastuzumab (TZ), a recombinant humanized monoclonal antibody that recognizes the extracellular domain of the HER2 protein, has dramatically altered the natural history of HER2-positive (HER2 + ) BC and ranks among the most significant advances in cancer therapeutics. 3,4 Nevertheless, in order to have a benefit from TZ or related therapies, the detection of HER2 expression remains a fundamental issue. Nowadays, HER2 expression is evaluated in postsurgery or bioptic specimen by immunohistochemistry (IHC) or fluorescence in situ hybridization 5 on the primary lesion.…”