A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer.
A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer.
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DOI：
10.1038/bjc.1998.584
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发表时间：
1998-09
影响因子：
8.8
通讯作者：
Blomqvist, C
中科院分区：
文献类型：
--
作者：
Sjostrom, J;Krajewski, S;Franssila, K;Niskanen, E;Wasenius, V M;Nordling, S;Reed, J C;Blomqvist, C
这项研究旨在确定可以预测乳腺癌化疗反应的因素。从1987年11月至1991年1月，173例可测量或可评价的转移性乳腺癌患者参加了一项随机试验，接受每月剂量的5-氟尿嘧啶(500 mg m(-2))、表阿霉素(60 mg m(-2))和环磷酰胺(500 mg m(-2))，作为一线细胞毒治疗，每4周一次或每4周一次。对103例可评价的肿瘤生物学因素，即组织学分级、雌激素受体(ER)、孕激素受体(PR)、S时相比例(SPF)、倍体、P53、c-erb B-2、Bcl2和Bax的表达进行多因素分析。在单变量分析中，只有SPF、分级和促凋亡蛋白Bax与细胞毒治疗的反应相关。在多变量分析中，SPF的相关性最强，其次是等级和Bax。在单因素分析分级中，PR、Bax、Bcl2与TTP显著相关，而在多因素分析中，仅PR与TTP显著相关。在单因素分析中，PR、Bax与OS相关，在多因素分析中，PR和Bax均保留其显着性。在单因素分析中，与细胞毒治疗反应显著相关的因素，即分级、SPF和Bax，在多因素分析中似乎也独立地预测治疗反应。TTP和OS在一定程度上可以由相同的因素预测，尽管相关性相当弱。需要更多的研究和新的肿瘤生物学因素来确定从化疗中受益最大的乳腺癌患者群体。
The study was designed to identify factors that could predict response to chemotherapy in breast cancer. A total of 173 patients with measurable or evaluable metastatic breast cancer were enrolled in a randomized trial between November 1987 and January 1991 to receive a monthly dose of 5-fluorouracil (500 mg m(-2)), epirubicin (60 mg m(-2)) and cyclophosphamide (500 mg m(-2)) either administered in four weekly doses or in an every-4-week dose as first-line cytotoxic treatment. In 103 evaluable patients we performed a multivariate analysis of the tumour biological factors, i.e. histological grade, oestrogen receptor (ER), progesterone receptor (PR), S-phase fraction (SPF), ploidy, p53, c-erbB-2, Bcl-2 and Bax expression, which showed significance in the univariate analysis according to treatment response, time to progression (TTP) or overall survival (OS). In the univariate analysis only SPF, grade and the proapoptotic protein Bax correlated with the response to cytotoxic treatment. In the multivariate analysis SPF had the strongest correlation, followed by grade and Bax. In the univariate analysis grade, PR, Bax and Bcl-2 correlated significantly with TTP, whereas in the multivariate analysis only PR showed a statistically significant correlation. In the univariate analysis PR and Bax correlated with OS and both retained its significance in the multivariate analysis. The factors that correlated significantly with the response to cytotoxic treatment in the univariate analysis, i.e. grade, SPF and Bax, seemed to predict independently the response to treatment in the multivariate analysis also. TTP and OS could be predicted partly by the same factors, although the association was quite weak. More studies and new tumour biological factors are needed to identify the group of breast cancer patients who get the most benefit from chemotherapy.