Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer
Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer
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DOI：
10.1200/jco.2002.08.125
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发表时间：
2002-05-01
影响因子：
45.3
通讯作者：
Seidman, AD
中科院分区：
文献类型：
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作者：
Van Poznak, C;Tan, L;Seidman, AD
目的：紫杉烷类化合物影响微管蛋白聚合，干扰有丝分裂转化。在G（1）-S边界的检查点阻断有望通过可能涉及p27的机制促进紫杉烷诱导的凋亡性细胞死亡。其他提出的临床紫杉烷敏感性/耐药性的决定因素包括p53、表皮生长因子受体（EGFR）超家族成员（例如，HER 2、EGFR）以及雌激素受体和孕酮受体。这些分子标志物及其与临床紫杉烷敏感性的相关性在这项回顾性临床病理研究中进行了研究。我们对雌激素受体、孕激素受体、HER 2、EGFR、p53、和p27在144例转移性乳腺癌患者的乳腺肿瘤标本中进行了一系列的单-药物紫杉烷化疗与临床反应（完全或部分反应）的相关性。患者的特征可能会影响反应（即，性能状态，疾病的程度，和先前的治疗）也进行了检查。在单变量分析中，Karnofsky体力状态≥ 90%和既往无蒽环类药物治疗史与紫杉烷单药治疗的良好临床反应相关（分别为P = 0.003和P = 0.041）。尽管p27阴性显示出显著性趋势（P = 0.075），但检测的IHC变量均不能预测紫杉烷治疗的临床反应。多克隆抗体与HercepTest之间的一致性（DAKO，Carpinteria，CA）和单克隆抗体CB-11（BioGenex，San Ramon，CA）（kappa = 0.943）;然而，单变量和多变量分析均未显示HER 2状态与紫杉烷化疗反应之间存在关联。研究的IHC生物标志物不能预测转移性乳腺癌患者对紫杉烷单药化疗的反应。确定紫杉烷反应的分子相关性仍然是一个重要的目标。(C)2002年，美国临床肿瘤学会。
Purpose : The taxanes affect tubulin polymerization and interfere with mitotic transition. A checkpoint blockade at the G(1)-S boundary would be expected to promote taxane-induced apoptotic cell death through a mechanism that may involve p27. Other proposed determinants of clinical taxane sensitivity/resistance include p53, members of the epidermal growth factor receptor (EGFR) superfamily (eg, HER2, EGFR), and estrogen receptors and progesterone receptors. These molecular markers and their correlation with clinical taxane sensitivity are investigated in this retrospective clinicopathologic study.Patients and Methods: We performed immunohistochemistry (IHC) for estrogen receptors, progesterone receptors, HER2, EGFR, p53, and p27 on 144 breast tumor specimens from patients treated for metastatic breast cancer on a series of clinical trials of single-agent taxane chemotherapy for correlation with clinical response (complete or partial response). Patient characteristics that could influence response (ie, performance status, extent of disease, and prior therapy) were also examined.Results. In univariate analysis, Karnofsky performance status a greater than or equal to 90% and no prior history of anthracycline therapy correlated with a good clinical response to single-agent taxane (P =.003 and P =.041, respectively). None of the IHC variables tested were predictive of clinical response to taxane therapy, although p27 negativity showed a trend toward significance (P =.075). Concordance between the polyclonal antibody with HercepTest (DAKO, Carpinteria, CA) and the monoclonal antibody CB-11 (BioGenex, San Ramon, CA) was noted (kappa = 0.943); however, neither univariate nor multivariate analysis demonstrated an association between HER2 status and response to taxane chemotherapy.Conclusion: The IHC biomarkers studied were not predictive of response to single-agent taxane chemotherapy in patients with metastatic breast cancer. Identification of molecular correlates of taxane response remains an important goal. (C), 2002 by American Society of Clinical Oncology.