Tubiana M, Koscielny S
Bull Cancer. 1987;74(1):43-57.
The most important event during the growth of a human cancer is the occurrence of distant spread. A model of the natural history of breast cancer was developed which was used for several aims. It has been possible to study the relationship between the size of the breast tumor and the probability of dissemination either in regional lymph nodes or in distant sites. It was found that the distribution of tumor volume at metastatic dissemination is log normal with a median (termed V50) of 23.6 ml (diameter 3.5 cm). The number of involved axillary lymph nodes and the histological grade have both an impact on the dissemination probability and the size of the V50. It is also possible to estimate the median volume of the primary at the involvement of the first axillary node, of the second, of the third... On average, the V50 for distant metastatic dissemination is greater than the volume of the tumor at the initiation of the second axillary node but smaller than the volume at the initiation of the third. Another study was the assessment of the time at which the metastases were initiated. The results concerning age of metastases at the time of initial treatment allow to estimate the reduction in the incidence of distant metastases which can be obtained by an earlier diagnosis; these estimations are consistent with data of screening programs. The size of the occult metastases at the time of treatment of primary tumor was calculated. It was found that this size is much larger in the subset of patients with pejorative prognostic factors which probably explains the relatively low effectiveness of adjuvant chemotherapy in these patients. The maximum size of the metastases which are controlled by adjuvant chemotherapy was found equal to 1.5.10(6) cells. Finally the model was used to investigate the possible dissemination arising from loco-regional recurrence. The discrepancy between the great reduction in the incidence of loco-regional recurrences obtained with post-operative radiotherapy and its relatively small impact on survival is probably due to the fact that a recurrence has an impact on survival only in patients without distant metastases at the time of initial treatment and in whom the recurrence was not detected and treated before it reached the size at which it can initiate a metastasis. This situation is likely to occur only in patients with tumors of the inner quadrants in whom the internal mammary chain has a great likelihood of being involved.
人类癌症发展过程中最重要的事件是远处转移的发生。我们建立了一个乳腺癌自然病史模型，该模型用于多个目的。通过这个模型，得以研究乳腺肿瘤大小与区域淋巴结或远处转移概率之间的关系。研究发现，发生转移时肿瘤体积的分布呈对数正态分布，中位数（称为V50）为23.6毫升（直径3.5厘米）。腋窝淋巴结受累数量和组织学分级均对转移概率及V50大小有影响。还能够估算出首个腋窝淋巴结、第二个、第三个……受累时原发肿瘤的中位数体积。平均而言，远处转移的V50大于第二个腋窝淋巴结开始受累时肿瘤的体积，但小于第三个腋窝淋巴结开始受累时肿瘤的体积。另一项研究是对转移起始时间的评估。关于初始治疗时转移灶年龄的结果有助于估算通过早期诊断可降低的远处转移发生率；这些估算结果与筛查项目的数据一致。计算了原发性肿瘤治疗时隐匿性转移灶的大小。结果发现，在具有不良预后因素的患者亚组中，隐匿性转移灶的大小要大得多，这可能解释了辅助化疗在这些患者中效果相对较低的原因。发现辅助化疗可控制的转移灶最大大小为1.5×10⁶个细胞。最后，该模型用于研究局部区域复发可能导致的转移情况。术后放疗使局部区域复发发生率大幅降低，但其对生存率的影响相对较小，两者之间的差异可能是由于只有在初始治疗时无远处转移且复发未被检测到并在其达到能够引发转移的大小之前未得到治疗的患者中，复发才会对生存率产生影响。这种情况可能仅发生在内象限肿瘤患者中，因为这些患者的乳内链很可能受累。
