Arizona Cancer Center, Tucson, Arizona 85724, USA.
Clin Cancer Res. 2010 Feb 15;16(4):1281-8. doi: 10.1158/1078-0432.CCR-09-1643. Epub 2010 Feb 9.
It has been suggested that a subgroup of human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with chromosome 17 (Chr-17) polysomy benefit from HER2-directed therapy. This hypothesis was examined using the data from a phase III trial that randomized patients with HER2-negative or HER2-untested metastatic breast cancer to first-line therapy with paclitaxel along with either lapatinib or placebo.
HER2 expression level by immunohistochemistry, fluorescence in situ hybridization (FISH), and mean HER2 ratio of Chr-17 values were determined centrally using archival tissue. Polysomy means of 2.0 and 2.2 served as thresholds.
Of 580 patients on the original trial, 406 were HER2 negative by FISH. Progression-free survival (PFS) data were available for 405 patients, of whom 44 (11%) met the definition of polysomy (Chr-17 >or=2.2, FISH negative for HER2). Median PFS in the polysomy group was 20.9 and 24.4 weeks for paclitaxel plus lapatinib and paclitaxel plus placebo, respectively. In the nonpolysomy group, median PFS was 24.6 and 23.1 weeks for paclitaxel plus lapatinib and paclitaxel plus placebo, respectively. Log-rank testing showed no treatment advantage for either group. Similar results were found using a Chr-17 polysomy cutoff of 2.0. Response rates in the polysomy group were 17% for paclitaxel plus lapatinib and 10% for paclitaxel plus placebo. In the nonpolysomy group, response rates were 32% for paclitaxel plus lapatinib and 25% for paclitaxel plus placebo. Neither comparison was statistically significant.
This analysis could not confirm the hypothesis that Chr-17 polysomy in HER2-nonamplified patients improved chemotherapy outcome when lapatinib is added as a HER2-targeted treatment.
有人提出，人表皮生长因子受体 2（HER2）阴性乳腺癌患者中存在染色体 17（Chr-17）多倍体亚群，这些患者从 HER2 靶向治疗中获益。本研究通过一项 III 期临床试验的数据对此假说进行了检验，该试验将 HER2 阴性或 HER2 未检测到的转移性乳腺癌患者随机分配到一线治疗方案中，即紫杉醇联合拉帕替尼或安慰剂治疗。
使用存档组织，通过免疫组织化学、荧光原位杂交（FISH）和 Chr-17 值的平均 HER2 比值的中心测定，确定 HER2 表达水平。多倍体的阈值为 2.0 和 2.2。
原始试验中 580 例患者，406 例 FISH 检查结果为 HER2 阴性。405 例患者有进展无进展生存（PFS）数据，其中 44 例（11%）符合多倍体定义（Chr-17≥2.2，HER2 阴性 FISH）。多倍体组的中位 PFS 分别为紫杉醇联合拉帕替尼和紫杉醇联合安慰剂的 20.9 和 24.4 周。非多倍体组的中位 PFS 分别为紫杉醇联合拉帕替尼和紫杉醇联合安慰剂的 24.6 和 23.1 周。对数秩检验显示两组均无治疗优势。使用 Chr-17 多倍体的截断值为 2.0 时，也得到了类似的结果。多倍体组中紫杉醇联合拉帕替尼的缓解率为 17%，而紫杉醇联合安慰剂的缓解率为 10%。非多倍体组中，紫杉醇联合拉帕替尼的缓解率为 32%，而紫杉醇联合安慰剂的缓解率为 25%。两种比较均无统计学意义。
本分析不能证实 Chr-17 多倍体增加了 HER2 非扩增患者的化疗效果，当拉帕替尼作为 HER2 靶向治疗药物添加时。
