The Ottawa Hospital Cancer Centre, Division of Medical Oncology, Department of Medicine, The University of Ottawa, 501 Smyth Road, Box 912, Ottawa, Ontario, Canada.
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?
曲妥珠单抗联合化疗治疗人表皮生长因子受体 2（HER2）可改善转移性和早期 HER2 过表达乳腺癌患者的总生存期。本文系统综述了 HER2 阳性乳腺癌新辅助临床试验数据，并讨论了尚未解决的关键临床问题。通过对 2000 年至 2011 年期间的 Pubmed®和 Biosis®的非时间限制搜索以及会议摘要书籍搜索，确定了所有针对 HER2 靶向新辅助治疗的试验。合格试验为前瞻性试验，至少有 10 例患者和明确的病理完全缓解（pCR）率定义。共有 50 项试验符合入选标准；确定了 41 项单臂 II 期研究，其中 37 项采用曲妥珠单抗，4 项采用拉帕替尼，基线肿瘤特征和 pCR 率存在显著差异（范围 12-66.7%）。在 9 项随机 II/III 期试验中，有 4 项评估了曲妥珠单抗联合化疗的效果，另外 5 项随机试验评估了不同的 HER2 靶向方法。其中 4 项研究评估了双重 HER2 靶向方法，当 lapatinib 而不是 pertuzumab 加入曲妥珠单抗时，这些方法普遍增加了 pCR，但增加了非心脏毒性。在 HER2 靶向方面取得了重大进展，导致接受肿瘤 pCR 的乳腺癌患者数量显著增加。需要等待随机新辅助和辅助研究的成熟数据来获得联合靶向方法的生存结果。未解决的问题集中在个体化治疗方面，包括：如果使用任何化疗方案，哪些患者需要双重 HER2 阻断？
