title: Management of ErbB2-positive breast cancer: insights from preclinical and clinical studies with lapatinib.
abstract: The management of human epidermal growth factor receptor 2-positive (ErbB2+) breast cancer is challenging; patients with ErbB2+ breast tumors have more aggressive disease and a poor prognosis. The increasing incidence of breast cancer in Asia and the limitations of existing treatments pose additional challenges. In this review, we summarize the preclinical and clinical evidence that indicates how lapatinib, a novel inhibitor that targets the human epidermal growth factor receptor (ErbB1) and ErbB2 may help clinicians address four particularly challenging issues in the management of ErbB2+ breast cancer. These issues are: (i) trastuzumab therapy failure, (ii) development of central nervous system metastases, (iii) minimizing toxicity and (iv) selecting the most appropriate partners (chemotherapy and non-chemotherapy) for combination therapy with lapatinib. Lapatinib, in combination with chemotherapeutic agents, such as capecitabine, provides clinical benefits to patients with ErbB2+ breast cancer, including patients who develop progressive disease on trastuzumab. Lapatinib, in combination with non-chemotherapeutic agents, such as letrozole, may also provide a chemotherapy-free treatment option for postmenopausal patients with estrogen receptor-positive/ErbB2+ metastatic breast cancer. Encouraging results have also emerged regarding the synergistic effects of lapatinib in combination with other agents for the treatment of ErbB2+ breast cancer. Promising findings have also been reported for the use of lapatinib to prevent and treat central nervous system metastases. Collectively, these results indicate that the judicious use of lapatinib, an effective oral therapy with a manageable toxicity profile, can enhance the management of patients with ErbB2+ breast cancer.
authors.affiliation: Sylvester Comprehensive Cancer Center at Deerfield Beach, University of Miami Miller School of Medicine, 1192 East Newport Center Drive, Deerfield Beach, FL 33442, USA. drcvogel@aol.com
authors.forename: Charles
authors.initials: C
authors.lastname: Vogel
authors.forename: Arlene
authors.initials: A
authors.lastname: Chan
authors.forename: Brunilde
authors.initials: B
authors.lastname: Gril
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Junichi
authors.initials: J
authors.lastname: Kurebayashi
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Yen-Shen
authors.initials: YS
authors.lastname: Lu
authors.forename: Hanlim
authors.initials: H
authors.lastname: Moon
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D000077341:Lapatinib; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases