Current standards in the treatment of metastatic breast cancer with focus on Lapatinib: a review by a Central European Consensus Panel

Abstract

In breast cancer, early detection as well as new developments in therapeutic options has resulted in less patients presenting with metastatic disease. However, about one-third of women with early stage breast cancer will eventually develop metastatic disease. Furthermore, approximately 20-30% of patients with breast cancer have tumors that overexpress human epidermal growth factor receptor (HER-2), which is associated with an aggressive tumor phenotype and poor prognosis. The identification of the HER-2 protein led to the development of highly effective therapeutics directed at this receptor. Trastuzumab, a recombinant, humanized, monoclonal antibody that binds to the extracellular domain of the HER-2 protein, has shown significant clinical benefit in metastatic and early-stage HER-2-positive breast cancer. Since the cancer recurs after adjuvant therapy in some women, and metastatic breast cancer eventually develops resistance to trastuzumab, there is a need for alternative treatment modalities to block HER-2 signaling. One of these treatment options is lapatinib, an orally active small molecule that inhibits the tyrosine kinases of HER-2 and the epidermal growth factor receptor type 1 (EGFR). In this consensus statement current treatment options in metastatic and locally advanced disease are discussed with a special focus on lapatinib.

Targeting invadopodia to block breast cancer metastasis

“…HER-2 (human epidermal growth factor receptor 2) status is an important clinical marker for treatment, with about 30% of patients presenting increased levels of HER-2expression[33]. Patients that are HER-2 positive are considered candidates for treatment with HER-2 inhibitors, including trastuzumab (Herceptin, Genentech) and lapatinib (Tykerb/Tyverb GSK)[36]. Recently, new small molecule-based therapeutics targeting EGFR, including erlotinib (Tarceva, OSI Pharmaceuticals), have proven useful in other cancers with upregulation of EGFR signaling[37].…”

Lapatinib in Breast Cancer - The Predictive Significance of Her1 (Egfr), Her2, Pten and Pik3ca Genes and Lapatinib Plasma Level Assessment

“…Both trastuzumab, and lapatinib, have been approved by the FDA and the European Medicines Agency (EMEA) for BC treatment. Lapatinib (Tykerb/Tyverb) was FDA approved in 2007 for use in combination with capecitabine for the treatment of HER2-positive (HER2+) advanced or MBC in patients who had received previous treatment (including anthracycline, taxane and trastuzumab containing regimens) and in 2010 it was approved in combination with letrozole for postmenopausal women with hormonal receptor positive and HER2+ MBC 8,10,[17][18][19][20] . TKIs are cheaper and easier to produce than monoclonal antibodies 21 .…”

Advances and Prospects in Cancer Immunotherapy

“…Overexpression of HER-2 has been shown to be associated with an aggressive tumor phenotype and poor prognosis [101]. Trastuzumab (Herceptin) is a recombinant, humanized, monoclonal antibody that binds to the extracellular domain of the HER-2 protein.…”

“…Trastuzumab (Herceptin) is a recombinant, humanized, monoclonal antibody that binds to the extracellular domain of the HER-2 protein. Trastuzumab has been approved by the FDA and clinical trials have shown its efficacy for metastatic and early-stage HER-2-positive breast cancer [101,102].…”