Clahsen P C, van de Velde C J, Duval C, Pallud C, Mandard A M, Delobelle-Deroide A, van den Broek L, Sahmoud T M, van de Vijver M J
European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium.
J Clin Oncol. 1998 Feb;16(2):470-9. doi: 10.1200/JCO.1998.16.2.470.
Thirty percent of women with node-negative breast cancer will have a recurrence within 10 years after diagnosis. Molecular markers may identify those patients and predict whether they benefit from adjuvant therapy. The European Organization for Research and Treatment of Cancer (EORTC) conducted a randomized trial (EORTC 10854) to compare perioperative treatment with one course of fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus no further therapy. We studied tumors from premenopausal patients with node-negative breast cancer randomized in this trial to determine whether p53 accumulation, c-erbB-2 expression, percentage of Ki-67-positive cells, estrogen receptor (ER-immunoassay [IA]), progesterone receptor (PR-IA), and angiogenesis could be used as prognostic factors and predictors of responsiveness to adjuvant chemotherapy.
Paraffin-embedded tumor specimens from 441 premenopausal women with node-negative breast cancer were collected from the larger EORTC trial. Paraffin sections from the tumors were analyzed for immunohistochemical expression of p53, c-erbB-2, Ki-67, ER, PR, and angiogenesis.
Patients with p53-negative tumors showed a significant benefit from perioperative chemotherapy (P < .01), whereas patients who had p53-positive tumors did not (P = .80). At a median follow-up time of 49 months, univariate analyses for disease-free survival (DFS) failed to show prognostic value for p53, c-erbB-2 and angiogenesis. Both univariate and multivariate results showed Ki-67 positivity, ER-IA negativity, and a younger age to be associated with a worse prognosis.
p53 accumulation was associated with a poor response to one perioperative course of FAC chemotherapy. Ki-67, ER-IA, and age are important prognostic factors in premenopausal women with node-negative breast cancer.
30%的淋巴结阴性乳腺癌女性患者在确诊后10年内会复发。分子标志物可识别这些患者，并预测她们是否能从辅助治疗中获益。欧洲癌症研究与治疗组织（EORTC）开展了一项随机试验（EORTC 10854），比较围手术期氟尿嘧啶、多柔比星和环磷酰胺（FAC）一个疗程的治疗与不进行进一步治疗的效果。我们研究了该试验中随机分组的绝经前淋巴结阴性乳腺癌患者的肿瘤，以确定p53积聚、c-erbB-2表达、Ki-67阳性细胞百分比、雌激素受体（ER免疫测定[IA]）、孕激素受体（PR-IA）和血管生成是否可作为预后因素及辅助化疗反应的预测指标。
从规模更大的EORTC试验中收集了441例绝经前淋巴结阴性乳腺癌女性患者的石蜡包埋肿瘤标本。对肿瘤的石蜡切片进行p53、c-erbB-2、Ki-67、ER、PR和血管生成的免疫组化表达分析。
p53阴性肿瘤患者从围手术期化疗中显著获益（P <.01），而p53阳性肿瘤患者则未获益（P =.80）。在中位随访时间49个月时，无病生存期（DFS）的单因素分析未显示p53、c-erbB-2和血管生成具有预后价值。单因素和多因素结果均显示，Ki-67阳性、ER-IA阴性和年龄较小与预后较差相关。
p53积聚与围手术期一个疗程FAC化疗反应不佳相关。Ki-67、ER-IA和年龄是绝经前淋巴结阴性乳腺癌女性重要的预后因素。
