Vargas-Roig L M, Gago F E, Tello O, Martin de Civetta M T, Ciocca D R
Laboratory of Reproduction and Lactaction, Regional Center for Scientific and Technological Research, Mendoza, Argentina.
Int J Cancer. 1999 Apr 20;84(2):129-34. doi: 10.1002/(sici)1097-0215(19990420)84:2<129::aid-ijc6>3.0.co;2-4.
Expression of c-erbB-2 protein has been associated with poor prognosis and poor response to chemotherapy in breast cancer patients. In the present prospective study, we have analyzed whether c-erbB-2, p53 and P170 proteins may be determinants of tumor resistance in locally advanced breast cancer patients treated with induction chemotherapy. Biopsies (n = 60) were examined by immuno-histochemistry; in 62% of cases core or incisional biopsies were taken before drug administration, allowing comparison in paired biopsies of the cytological and molecular changes induced by treatment Sixty percent of the patients received relatively high doses of FAC or FEC (5-fluorouracil, doxorubicin or epirubicin and cyclophosphamide), and 40% received relatively high doses of doxorubicin or epirubicin alone. No significant changes were observed in the molecular markers studied following chemotherapy; in the few biopsies where changes appeared, the changes did not exhibit any significant or similar trend. For 30 of the patients who received FAC/FEC treatment, follow-up reached a median of 34 months. In these cases, neither the clinical (reduction in tumor size) nor the histological (evaluated after neoadjuvant chemotherapy) responses showed statistically significant differences between the patients who developed distant metastases and the disease-free patients. c-erbB-2 was over-expressed in 50% of patients who developed distant metastases vs. 7% of the disease-free patients. Disease free survival (DFS) curves between c-erbB-2-positive and c-erbB-2-negative patients were statistically significant. No correlation between p53 or P170 expression with DFS was found. Our results suggest that c-erbB-2 protein expression is associated with development of distant metastases in breast cancer patients treated with relatively high doses of anthracyclines in induction chemotherapy.
c-erbB-2蛋白的表达与乳腺癌患者预后不良及化疗反应差有关。在本项前瞻性研究中，我们分析了c-erbB-2、p53和P170蛋白是否可能是接受诱导化疗的局部晚期乳腺癌患者肿瘤耐药性的决定因素。通过免疫组织化学检查活检样本（n = 60）；62%的病例在给药前进行了粗针或切开活检，从而能够在配对活检中比较治疗引起的细胞学和分子变化。60%的患者接受了相对高剂量的FAC或FEC（5-氟尿嘧啶、多柔比星或表柔比星以及环磷酰胺），40%的患者仅接受了相对高剂量的多柔比星或表柔比星。化疗后所研究的分子标志物未观察到显著变化；在少数出现变化的活检样本中，这些变化未呈现出任何显著或相似的趋势。对于30例接受FAC/FEC治疗的患者，随访时间中位数达到34个月。在这些病例中，发生远处转移的患者与无病患者之间，无论是临床反应（肿瘤大小缩小）还是组织学反应（新辅助化疗后评估）均未显示出统计学上的显著差异。发生远处转移的患者中有50%的c-erbB-2呈过表达，而无病患者中这一比例为7%。c-erbB-2阳性和c-erbB-2阴性患者的无病生存（DFS）曲线具有统计学显著性。未发现p53或P170表达与DFS之间存在相关性。我们的结果表明，在诱导化疗中接受相对高剂量蒽环类药物治疗的乳腺癌患者中，c-erbB-2蛋白表达与远处转移的发生有关。
