Prediction of response to neoadjuvant chemoendocrine therapy in primary breast carcinomas.
Prediction of response to neoadjuvant chemoendocrine therapy in primary breast carcinomas.
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发表时间：
1997-04
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通讯作者：
A. Makris;T. Powles;M. Dowsett;C. Osborne;P. Trott;I. Fernando;S. Ashley;M. Ormerod;J. Titley;R. Gregory;D. Allred
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作者：
A. Makris;T. Powles;M. Dowsett;C. Osborne;P. Trott;I. Fernando;S. Ashley;M. Ormerod;J. Titley;R. Gregory;D. Allred
我们的目的是确定生物分子标志物是否可以预测早期乳腺癌患者对新辅助化疗内分泌治疗的反应。研究对象为90例可手术乳腺癌患者，中位年龄56岁，年龄28-69岁。他们在手术前接受了四个周期的化疗，每周四个周期，用丝裂霉素C(+/-丝裂霉素C)和他莫昔芬。治疗前采用细针抽吸法检测雌激素受体(ER)、孕激素受体(PgR)，免疫细胞化学检测P53、Ki67、Bcl2、c-erb B-2，流式细胞仪检测细胞倍体及S期细胞比例(SPF)。78%的受试者肿瘤有反应(完全缓解，9%；部分缓解，69%)，22%没有变化(无变化，20%；进展性疾病，2%)。不同病期、不同年龄的缓解率分别为：T1 74%、T2 79%、T3/T4 78%、50岁79%(P=0.0 5)。其他指标的有效率分别为：ER阳性82%，阴性70%；PGR阳性86%，阴性71%；p53阳性74%，阴性81%；bcl2阳性85%，阴性61%；c-erbB 2阳性57%，阴性93%；Ki67高，77%，低，81%；SPF高，77%，低，77%；异倍体，71%；二倍体，85%。仅c-erb B-2差异有统计学意义(P=0.007)。对于ER、PGR和Bcl2阳性的肿瘤，观察到对新辅助化疗内分泌治疗的有效率更高的趋势，但没有达到统计学意义。C-erbB-2阴性的肿瘤有较高的有效率，有统计学意义。相比之下，Ki67、倍体、SPF和P53未能预测疗效。
Our aim was to determine whether biological molecular markers can predict response to neoadjuvant chemoendocrine therapy in patients with early breast cancer. Ninety patients (median age 56 years; range, 28-69 years) with primary operable breast carcinoma were studied. They were treated with four 3-weekly cycles of chemotherapy with mitozantrone, methotrexate (+/- mitomycin C), and tamoxifen prior to surgery. Fine-needle aspiration was used to obtain samples from patients prior to therapy, and the following parameters were assessed: estrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, Bcl-2, and c-erbB-2 measured by immunocytochemistry, and ploidy and S-phase fraction (SPF) by flow cytometry. The tumors of 78% of the subjects responded (complete response, 9%; partial response, 69%) and 22% did not (no change, 20%; progressive disease, 2%). Response rates according to disease stage and patient age were as follows: T1, 74%; T2, 79%; T3/T4, 78%; age 50, 79% (P = not significant). Response rates for other parameters were as follows: ER-positive, 82%, and -negative, 70%; PgR-positive, 86%, and -negative, 71%; p53-positive, 74%, and -negative, 81%; Bcl-2-positive, 85%, and -negative 61%; c-erbB-2-positive, 57%, and -negative, 93%; Ki67 high, 77%, and low, 81%; SPF high, 77%, and low, 77%; aneuploid, 71%; and diploid, 85%. Only the difference for c-erbB-2 was statistically significant (P = 0.007). A trend for higher response rates to neoadjuvant chemoendocrine therapy for tumors that were positive for ER, PgR, and Bcl-2 was observed but did not reach statistical significance. Tumors negative for c-erbB-2 had a higher response rate, which was statistically significant. In contrast, Ki67, ploidy, SPF, and p53 failed to predict for response.