Medical Oncology Service, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain.
Clin Breast Cancer. 2013 Apr;13(2):146-52. doi: 10.1016/j.clbc.2012.11.006. Epub 2013 Jan 11.
To assess the molecular subtypes determined by hormonal receptors (HR) and human epidermal growth factor receptor 2 (HER2) status and the role of proliferation measured by the Ki-67 marker as predictive and prognostic factors in breast cancer patients treated with neoadjuvant chemotherapy.
A total of 127 breast cancer patients were treated with neoadjuvant chemotherapy every 2 weeks as part of 2 studies. Study A consisted of the administration of Adriamycin (40 mg/m(2)) on day 1 plus paclitaxel (150 mg/m(2)) and gemcitabine 2000 mg/m(2)) on day 2 for 6 cycles (n = 54). Study B consisted of the administration of epirubicin (90 mg/m(2)), cyclophosphamide (600 mg/m(2)) on day 1 for 3 cycles, followed by the administration of paclitaxel (150 mg/m(2)) and gemcitabine 2500 (mg/m(2)) on day 1 with or without trastuzumab according to HER2 status (n = 73). In study A, patients did not receive trastuzumab regardless of HER2 status. The molecular subtypes of the patients with breast cancer were classified as 49% HR(+)/HER2(-), 17.5% HR(+)/HER2(+), 13.5% HR(-)/HER2(+), and 20% HR(-)/HER2(-).
Pathologic complete response (pCR), defined as the absence of invasive cells in the breast and the lymph nodes, was achieved in 35 (28%) patients. The pCR rate was significantly different between the molecular subtypes of breast cancer, with 9% in HR(+)/HER2(-), 23% in HR(+)/HER2(+), 50% in HR(-)/HER2(+), and 56% in HR(-)/HER2(-) tumors (P < .001). The pCR rate was significantly higher in tumors that had high Ki-67 (≥20%) expression and were HR(-). HER2(+) was associated with a higher trend of pCR but did not reach statistical significance. The median follow-up was 81 months (r = 15-150 months). Patients who achieved a pCR had a significantly lower recurrence (P = .01) and higher overall survival (P = .02) compared with those who did not achieve pCR. A multivariate analysis revealed that pCR (hazard ratio 0.24 [95% CI, 0.07-0.7]; P = .019), the molecular subtype (hazard ratio 0.3 [95% CI, 0.1-0.8]; P = .02), and the Ki-67 index (hazard ratio 3.2 [95% CI, 1.4-7.1]; P = .004) were significant independent predictors of disease-free survival. Similar results were obtained for overall survival, in which the pCR rate (hazard ratio 0.119 [95% CI, 0.028-0.5]; P = .004), the molecular subtype (hazard ratio 0.17 [95% CI, 0.03-0.86]; P = .02), and the Ki-67 index (hazard ratio 3.6 [95% CI, 1.3-9.7]; P = .01) also displayed a significant influence on survival.
Molecular subtypes and Ki-67 index were independent prognostic factors for disease-free survival and overall survival in breast cancer patients treated with neoadjuvant chemotherapy. A high rate of Ki-67 and HR(-) expression were predictors of pCR.
评估激素受体（HR）和人表皮生长因子受体 2（HER2）状态确定的分子亚型以及 Ki-67 标志物作为预测和预后因素在接受新辅助化疗的乳腺癌患者中的作用。
共有 127 例乳腺癌患者接受新辅助化疗，每 2 周进行一次，作为 2 项研究的一部分。研究 A 包括第 1 天给予阿霉素（40mg/m²），第 2 天给予紫杉醇（150mg/m²）和吉西他滨 2000mg/m²），共 6 个周期（n=54）。研究 B 由表柔比星（90mg/m²）、环磷酰胺（600mg/m²）组成，第 1 天给予 3 个周期，随后根据 HER2 状态给予紫杉醇（150mg/m²）和吉西他滨 2500mg/m²）（n=73）。在研究 A 中，无论 HER2 状态如何，患者均不接受曲妥珠单抗治疗。乳腺癌患者的分子亚型分为 49% HR（+）/HER2（-）、17.5% HR（+）/HER2（+）、13.5% HR（-）/HER2（+）和 20% HR（-）/HER2（-）。
病理完全缓解（pCR）定义为乳腺和淋巴结中无浸润细胞，35 例（28%）患者达到 pCR。乳腺癌的分子亚型之间的 pCR 率有显著差异，HR（+）/HER2（-）为 9%，HR（+）/HER2（+）为 23%，HR（-）/HER2（+）为 50%，HR（-）/HER2（-）为 56%（P<0.001）。Ki-67 高表达（≥20%）且 HR（-）的肿瘤 pCR 率显著较高。HER2（+）与 pCR 趋势较高相关，但未达到统计学意义。中位随访时间为 81 个月（r=15-150 个月）。与未达到 pCR 的患者相比，达到 pCR 的患者复发率显著降低（P=0.01），总生存率显著提高（P=0.02）。多变量分析显示，pCR（风险比 0.24[95%CI，0.07-0.7]；P=0.019）、分子亚型（风险比 0.3[95%CI，0.1-0.8]；P=0.02）和 Ki-67 指数（风险比 3.2[95%CI，1.4-7.1]；P=0.004）是疾病无进展生存的显著独立预测因素。总生存率也得到了类似的结果，其中 pCR 率（风险比 0.119[95%CI，0.028-0.5]；P=0.004）、分子亚型（风险比 0.17[95%CI，0.03-0.86]；P=0.02）和 Ki-67 指数（风险比 3.6[95%CI，1.3-9.7]；P=0.01）也对生存有显著影响。
分子亚型和 Ki-67 指数是新辅助化疗乳腺癌患者无病生存和总生存的独立预后因素。高 Ki-67 率和 HR（-）表达是 pCR 的预测因素。
