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dc.contributor.authorDent, S
dc.contributor.authorOyan, B
dc.contributor.authorHonig, A
dc.contributor.authorMano, M
dc.contributor.authorHowell, Sacha J
dc.date.accessioned2013-08-30T13:22:17Z
dc.date.available2013-08-30T13:22:17Z
dc.date.issued2013-10
dc.identifier.citationHER2-targeted therapy in breast cancer: a systematic review of neoadjuvant trials. 2013, 39 (6):622-31 Cancer Treat Reven_GB
dc.identifier.issn1532-1967
dc.identifier.pmid23434074
dc.identifier.doi10.1016/j.ctrv.2013.01.002
dc.identifier.urihttp://hdl.handle.net/10541/300427
dc.description.abstractTargeting human epidermal growth factor receptor 2 (HER2) during or in sequence with chemotherapy improves overall survival in metastatic and early HER2-overexpressing breast cancer. In this paper we systematically review neoadjuvant clinical trial data in HER2-positive breast cancer and discuss key unanswered clinical questions. All trials of HER2-targeted neoadjuvant therapy were identified through non-date-limited searches of PubMED® and Biosis® and congress abstract book searches from 2000-2011. Eligible trials were prospective, had at least 10 patients and a clear definition of pathological complete response (pCR) rate. A total of 50 trials fulfilled the eligibility criteria; 41 single-arm phase II studies were identified, 37 with trastuzumab and 4 with lapatinib, with significant variability in baseline tumour characteristics and pCR rates (range 12-66.7%). Of 9 randomised phase II/III trials, 4 assessed the addition of trastuzumab to chemotherapy and a further 5 randomised trials assessed different HER2-targeting approaches. Four of these studies assessed dual HER2-targeting approaches, which universally increased pCR at the expense of increased non-cardiac toxicity when lapatinib, but not pertuzumab, was added to trastuzumab. Significant advances have been made in HER2 targeting, resulting in a marked increase in the number of breast cancer patients experiencing tumour pCR. Mature data from randomised neoadjuvant and adjuvant studies are awaited for survival outcomes with combination targeted approaches. Unanswered questions centre on the individualisation of therapy and include; which, if any, chemotherapy backbone should be used, and which patients need dual HER2 blockade?
dc.language.isoenen
dc.rightsArchived with thanks to Cancer treatment reviewsen_GB
dc.subject.meshAntineoplastic Agents
dc.subject.meshBreast Neoplasms
dc.subject.meshClinical Trials, Phase II as Topic
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshMolecular Targeted Therapy
dc.subject.meshNeoadjuvant Therapy
dc.subject.meshReceptor, erbB-2
dc.titleHER2-targeted therapy in breast cancer: a systematic review of neoadjuvant trials.en
dc.typeArticleen
dc.contributor.departmentThe Ottawa Hospital Cancer Centre, Division of Medical Oncology, Department of Medicine, The University of Ottawa, 501 Smyth Road, Box 912, Ottawa, Ontario, Canada. sdent@Ottawahospital.on.caen_GB
dc.identifier.journalCancer Treatment Reviewsen_GB
html.description.abstractTargeting human epidermal growth factor receptor 2 (HER2) during or in sequence with chemotherapy improves overall survival in metastatic and early HER2-overexpressing breast cancer. In this paper we systematically review neoadjuvant clinical trial data in HER2-positive breast cancer and discuss key unanswered clinical questions. All trials of HER2-targeted neoadjuvant therapy were identified through non-date-limited searches of PubMED® and Biosis® and congress abstract book searches from 2000-2011. Eligible trials were prospective, had at least 10 patients and a clear definition of pathological complete response (pCR) rate. A total of 50 trials fulfilled the eligibility criteria; 41 single-arm phase II studies were identified, 37 with trastuzumab and 4 with lapatinib, with significant variability in baseline tumour characteristics and pCR rates (range 12-66.7%). Of 9 randomised phase II/III trials, 4 assessed the addition of trastuzumab to chemotherapy and a further 5 randomised trials assessed different HER2-targeting approaches. Four of these studies assessed dual HER2-targeting approaches, which universally increased pCR at the expense of increased non-cardiac toxicity when lapatinib, but not pertuzumab, was added to trastuzumab. Significant advances have been made in HER2 targeting, resulting in a marked increase in the number of breast cancer patients experiencing tumour pCR. Mature data from randomised neoadjuvant and adjuvant studies are awaited for survival outcomes with combination targeted approaches. Unanswered questions centre on the individualisation of therapy and include; which, if any, chemotherapy backbone should be used, and which patients need dual HER2 blockade?


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