Medical Oncology University Hospital, Service Oncologie, Boulevard Fleming, Besançon, Inserm U645, France.
Eur J Cancer. 2009 Nov;45(17):2940-6. doi: 10.1016/j.ejca.2009.07.015. Epub 2009 Aug 13.
Oestrogen receptor (ER)-negative breast cancer, including oestrogen receptor-, progesterone receptor- and human epidermal growth factor receptor 2-negative (ER/PR/HER2-negative) breast cancer, is more aggressive than ER-positive disease. A major limitation in the treatment of ER-negative disease subtypes is the inherent insensitivity to hormonal agents (tamoxifen, aromatase inhibitors) that are widely used in the treatment of breast cancer. Thus, therapeutic options for poor prognosis patients with ER-negative breast cancer are limited to a handful of chemotherapeutic agents, and new agents are needed to improve the treatment of this disease. Ixabepilone, a novel epothilone B analogue with low susceptibility to cellular mechanisms that confer resistance to taxanes and other chemotherapeutic agents, has demonstrated potent preclinical antitumour activity in multiple models, including those with primary or acquired drug resistance. This review summarises the results of a prospective subset analysis from a phase III clinical trial evaluating ixabepilone for the treatment of metastatic breast cancer (MBC), in which efficacy and safety were evaluated in patients with ER-negative and ER/PR/HER2-negative disease.
雌激素受体(ER)阴性乳腺癌,包括雌激素受体、孕激素受体和人表皮生长因子受体 2 阴性(ER/PR/HER2-阴性)乳腺癌,比 ER 阳性疾病更具侵袭性。ER 阴性疾病亚型治疗的主要局限性是对广泛用于乳腺癌治疗的激素药物(他莫昔芬、芳香酶抑制剂)固有不敏感。因此,ER 阴性乳腺癌预后不良患者的治疗选择仅限于少数几种化疗药物,需要新的药物来改善这种疾病的治疗。伊沙匹隆是一种新型埃坡霉素 B 类似物,对赋予紫杉醇和其他化疗药物耐药性的细胞机制的敏感性较低,在多种模型中显示出强大的临床前抗肿瘤活性,包括原发性或获得性耐药性模型。这篇综述总结了一项评估伊沙匹隆治疗转移性乳腺癌(MBC)的 III 期临床试验的前瞻性亚组分析结果,该试验评估了 ER 阴性和 ER/PR/HER2-阴性疾病患者的疗效和安全性。