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[在一小部分患者中,无细胞抑制和激素治疗情况下雌激素和孕激素受体对乳腺癌生存影响的论证]

[Demonstration of the effect of estrogen and progesterone receptors on survival in breast cancer without cytostatic and hormonal treatment in a small set of patients].

作者信息

Hochmann J

机构信息

Katedra biologických a lékarských ved FaF UK, Hradec Králové.

出版信息

Klin Onkol. 2010;23(1):25-33.

Abstract

BACKGROUND

With respect to diagnostic and therapeutic progress, it may occur that the statistical sets of patients evaluated and treated with uniform methods are small. As a consequence, it is meaningful to check a greater number of statistical approaches. It is suitable to verify whether, for instance, the differences between the results (+) and (++) for estrogen and progesterone receptors (ER and PR) in breast cancer have an effect on the length of survival. This question could be answered with the use of several Kaplan-Meier survival curves. However, it is also profitable to judge the simple graph of survival in dependence on receptor concentration. Nevertheless, traditional regression brings too great an error to this method of assessment. Therefore, the use of orthogonal regression is much more precise. Since it can be assumed that no non-revealable micro-metastases were present at the time of operation in some patients with N0, it is possible to achieve healing ad integrum of them using only simple surgery. Consequently, we concluded that it was necessary to exclude from the evaluation the group of patients in N0 surviving 10 years (in the search for evidence of the post-operative impact of age-based reduction of blood estrogen on survival).

DESIGN AND SUBJECTS

We verified these considerations when monitoring the ER and PR influence on overall survival. We performed this analysis in an approximately 2-year sample of 74 female patients who received the described treatment in Pardubice hospital. At the time of operation, 56 were postmenopausal and 21 of these postmenopausal patients were in stage N1.

METHODS AND RESULTS

ER and PR in breast tumours were examined in the cytosol of operational biopsies. Adjuvant radiological treatment was used in addition to the surgical treatment of primary tumours and their original and post-operative metastases. In the case of premenopausal patients with ER, (+) therapeutic sterilization was performed. The finding of higher ER in postmenopausal surviving patients (in comparison to dead ones) was below the boundary of statistical significance. Also, longer survival in cases of higher ER concentrations in the group of dead N1 patients was below the boundary of statistical significance in the use of traditional regression. Therefore, we put together evidence from the group of surviving patients with evidence from the group of dead patients. In the case of N1 patients surviving 10 years, we rounded their survival period to 15 years for inclusion in the graph of survival dependence on ER. In the case of the combined (premenopausal with postmenopausal) group, statistical reliability appeared for longer survival of higher ER already in traditional regression. However, for the postmenopausal alone, the difference was statistically insignificant. Nevertheless, if we used orthogonal regression (similar to Deming regression) instead of traditional regression, then the reliability of the dependence of the length of survival on ER increased (in the last cited graph) to such a degree that it was statistically highly significant (at the level of 0.001) even in case of just postmenopausal patients. The same level of statistical reliability was achieved in the Kaplan-Meier analysis. Also in the case of PR--the higher concentrations of this receptor in survivors compared to dead patients were not statistically significant. But (in contrast to ER) in the case of PR, we observed a statistically significant increase in survival time depending on the receptor concentration within the group of only the dead patients--hence without putting them together with the surviving patients).

CONCLUSIONS

The graph of the Kaplan-Meier analysis is more frequently used when solving these problems but the graph of simple dependence of survival on receptor concentration should not be neglected either because, for example, it better shows the difference in survival between ER(+) and (++). Nevertheless, it is necessary to use orthogonal regression in it. The greater suitability of PR and ER for short-term and long-term prognosis, respectively, which we identified in our statistical set, is in concordance with the literature.

摘要

背景

关于诊断和治疗进展,可能会出现采用统一方法评估和治疗的患者统计集规模较小的情况。因此,检查更多的统计方法是有意义的。例如,验证乳腺癌中雌激素和孕激素受体(ER和PR)结果(+)和(++)之间的差异是否对生存时长有影响是合适的。这个问题可以通过使用多条Kaplan-Meier生存曲线来回答。然而,根据受体浓度判断简单的生存图也是有益的。不过,传统回归给这种评估方法带来的误差太大。因此,使用正交回归要精确得多。由于可以假设在一些N0期患者手术时不存在不可检测的微转移,仅通过简单手术就有可能使他们完全康复。因此,我们得出结论,有必要在评估中排除存活10年的N0期患者组(以寻找基于年龄降低血液雌激素对生存的术后影响的证据)。

设计与研究对象

我们在监测ER和PR对总生存的影响时验证了这些考量。我们在帕尔杜比采医院接受所述治疗的74名女性患者的约2年样本中进行了此项分析。手术时,56名患者处于绝经后状态,其中21名绝经后患者处于N1期。

方法与结果

在手术活检的胞浆中检测乳腺肿瘤中的ER和PR。除了对原发性肿瘤及其原发和术后转移灶进行手术治疗外,还采用了辅助性放射治疗。对于ER为(+)的绝经前患者,进行了治疗性绝育。绝经后存活患者(与死亡患者相比)ER较高的发现低于统计学显著性界限。同样,在死亡的N1期患者组中,ER浓度较高的患者存活时间更长,在使用传统回归时也低于统计学显著性界限。因此,我们将存活患者组的证据与死亡患者组的证据汇总在一起。对于存活10年的N1期患者,我们将其生存期四舍五入为15年,以纳入生存依赖于ER的图表中。在联合(绝经前与绝经后)组中,在传统回归中,ER较高者存活时间更长这一点已经具有统计学可靠性。然而,仅对于绝经后患者,差异在统计学上不显著。尽管如此,如果我们使用正交回归(类似于Deming回归)而非传统回归,那么生存时长对ER的依赖性的可靠性(在最后引用的图表中)提高到了这样一个程度,即即使仅对于绝经后患者,其在统计学上也具有高度显著性(在0.001水平)。在Kaplan-Meier分析中也达到了相同水平的统计学可靠性。同样,对于PR而言,存活患者与死亡患者相比该受体浓度较高的情况在统计学上不显著。但是(与ER不同)对于PR,我们在仅死亡患者组中观察到根据受体浓度生存时间有统计学显著增加(因此未将他们与存活患者汇总在一起)。

结论

在解决这些问题时,Kaplan-Meier分析图更常被使用,但生存对受体浓度的简单依赖图也不应被忽视,因为例如它能更好地显示ER(+)和(++)之间的生存差异。然而,在其中有必要使用正交回归。我们在统计集中确定的PR和ER分别对短期和长期预后的更大适用性与文献一致。

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