Di Leo A, Chan S, Paesmans M, Friedrichs K, Pinter T, Cocquyt V, Murray E, Bodrogi I, Walpole E, Lesperance B, Korec S, Crown J, Simmonds P, Von Minckwitz G, Leroy J Y, Durbecq V, Isola J, Aapro M, Piccart M J, Larsimont D
Jules Bordet Institute, Brussels, UK.
Breast Cancer Res Treat. 2004 Aug;86(3):197-206. doi: 10.1023/B:BREA.0000036783.88387.47.
To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T).
Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect.
Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival.
These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.
评估HER-2在接受单药阿霉素（A）或单药多西他赛（T）随机治疗的晚期乳腺癌患者群体中的预测价值。
本研究中的患者参与了一项III期临床试验，其中阿霉素或多西他赛用于治疗晚期疾病。通过免疫组化（IHC）评估HER-2。在所有阳性病例中，使用荧光原位杂交（FISH）来确认HER-2阳性状态。对通过HER-2鉴定的不同患者队列进行检查，以评估HER-2状态与治疗效果之间的可能关系。
在进入临床试验的326例患者中，有176例（54%）可获得肿瘤样本。在20%的研究人群中观察到HER-2阳性。在对研究药物的反应率与HER-2状态之间发现了具有统计学意义的相互作用，HER-2阳性患者从使用T中获益最大（接受T治疗的HER-2阳性患者的优势比=3.12（95%置信区间1.11 - 8.80），p = 0.03）。多变量分析也证实了HER-2与对A和T的反应率之间的相互作用。在根据疾病进展时间和总生存期评估的HER-2与药物疗效之间未发现具有统计学意义的相互作用，尽管在HER-2阴性队列中，就总生存期而言A至少与T一样有效。
这些结果表明，在HER-2阳性乳腺癌患者中，多西他赛可能比阿霉素更具活性，而在HER-2阴性患者中，阿霉素可能至少与多西他赛一样有效。尽管目前的结果不会对当前的临床实践产生影响，但它们使我们能够提出这样的假设，即HER-2阳性乳腺癌在对蒽环类药物和紫杉烷类药物的敏感性方面是一种异质性疾病，这可能取决于包括p-53和拓扑异构酶IIα基因在内的其他分子标志物。目前正在两项不同的“从实验台到病床旁”的临床试验中对这一假设进行前瞻性测试。
