HER2-targeted therapy in breast cancer: a systematic review of neoadjuvant trials

Cancer Treat Rev. 2013 Oct;39(6):622-31. doi: 10.1016/j.ctrv.2013.01.002. Epub 2013 Feb 19.


Targeting 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?

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology
  • Clinical Trials, Phase II as Topic
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Neoadjuvant Therapy
  • Receptor, ErbB-2 / metabolism*


  • Antineoplastic Agents
  • Receptor, ErbB-2