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在新辅助治疗中使用芳香化酶抑制剂:是演进还是变革?

Using aromatase inhibitors in the neoadjuvant setting: evolution or revolution?

作者信息

Freedman O C, Verma S, Clemons M J

机构信息

Division of Medical Oncology, Toronto-Sunnybrook Regional Cancer Centre, 2075 Bayview Avenue, Toronto, Ont., Canada M4N 3M5.

出版信息

Cancer Treat Rev. 2005 Feb;31(1):1-17. doi: 10.1016/j.ctrv.2004.09.008. Epub 2004 Nov 18.

Abstract

Despite improvements in the management of patients with early breast cancer, the prognosis for women with locally advanced breast cancer (LABC) remains poor. The potential goals of neoadjuvant treatment for this disease include down-sizing tumours to allow breast conservation as well as the possibility of improving survival rates. Neoadjuvant treatment was initially dominated by chemotherapy, which increased rates of breast conserving surgery, but to date has demonstrated no survival benefit over standard adjuvant chemotherapy. With recent advances in endocrine therapy, and rapid and routine assessment of predictive factors of response such as estrogen (ER), progesterone (PR) and Her2 nu receptor status, endocrine therapy has come to the forefront of research investigating a neoadjuvant alternative to chemotherapy. Early studies of neoadjuvant endocrine therapy mainly evaluated the role of tamoxifen in the treatment of elderly postmenopausal women with LABC who were unselected for ER/PR status and were unsuitable for either surgery or chemotherapy. Response rates in these patients were found to be inferior to those traditionally obtained from trials with neoadjuvant chemotherapy. Paralleling the superiority that third-generation aromatase inhibitors have shown over tamoxifen in the metastatic and adjuvant settings however, AIs have also demonstrated superiority in the neoadjuvant setting. Recent studies have shown response rates for neoadjuvant treatment with aromatase inhibitors in carefully selected hormone receptor positive patients to be comparable to those seen with neoadjuvant chemotherapy. This is particularly important as hormone receptor positive tumours have repeatedly been shown to have lower response rates to neoadjuvant chemotherapy than hormone receptor negative tumours. Neoadjuvant endocrine treatment with aromatase inhibitors has therefore evolved from being an experimental effort to palliate women with LABC unsuitable for surgery or chemotherapy, to representing a viable and possibly preferred alternative for postmenopausal women with hormone receptor positive large tumours or LABC. Further benefits of neoadjuvant trials include allowing the study of predictive biomarkers of disease in order to provide insight into therapy resistance and sensitivity, and identifying promising systemic therapies for additional testing in larger adjuvant trials.

摘要

尽管早期乳腺癌患者的管理有所改善,但局部晚期乳腺癌(LABC)女性的预后仍然很差。这种疾病新辅助治疗的潜在目标包括缩小肿瘤大小以实现保乳,以及提高生存率的可能性。新辅助治疗最初以化疗为主,化疗提高了保乳手术的比例,但迄今为止,与标准辅助化疗相比,尚未显示出生存获益。随着内分泌治疗的最新进展,以及对雌激素(ER)、孕激素(PR)和Her2 nu受体状态等反应预测因素的快速常规评估,内分泌治疗已成为研究新辅助化疗替代方案的前沿领域。新辅助内分泌治疗的早期研究主要评估了他莫昔芬在治疗未选择ER/PR状态且不适合手术或化疗的老年绝经后LABC女性中的作用。这些患者的缓解率低于传统新辅助化疗试验所获得的缓解率。然而,与第三代芳香化酶抑制剂在转移性和辅助治疗中显示出优于他莫昔芬的优势相似,芳香化酶抑制剂在新辅助治疗中也显示出优势。最近的研究表明,在精心挑选的激素受体阳性患者中,芳香化酶抑制剂新辅助治疗的缓解率与新辅助化疗相当。这一点尤为重要,因为激素受体阳性肿瘤对新辅助化疗的缓解率一再被证明低于激素受体阴性肿瘤。因此,芳香化酶抑制剂新辅助内分泌辅助内分泌治疗已从一种旨在缓解不适合手术或化疗的LABC女性症状的实验性努力,发展成为激素受体阳性大肿瘤或LABC绝经后女性的一种可行且可能更优的选择。新辅助试验的进一步益处包括允许研究疾病的预测生物标志物,以便深入了解治疗耐药性和敏感性,并确定有前景的全身治疗方法,以便在更大规模的辅助试验中进行进一步测试。

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