Demicheli Romano, Biganzoli Elia, Boracchi Patrizia, Greco Marco, Retsky Michael W
Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milano, Italy.
Breast Cancer Res. 2008;10(5):R83. doi: 10.1186/bcr2152. Epub 2008 Oct 9.
The dynamics of breast cancer recurrence and death, indicating a bimodal hazard rate pattern, has been confirmed in various databases. A few explanations have been suggested to help interpret this finding, assuming that each peak is generated by clustering of similar recurrences and different peaks result from distinct categories of recurrence.
The recurrence dynamics was analysed in a series of 1526 patients undergoing conservative surgery at the National Cancer Institute of Milan, Italy, for whom the site of first recurrence was recorded. The study was focused on the first clinically relevant event occurring during the follow up (ie, local recurrence, distant metastasis, contralateral breast cancer, second primary tumour), the dynamics of which was studied by estimating the specific hazard rate.
The hazard rate for any recurrence (including both local and distant disease relapses) displayed a bimodal pattern with a first surge peaking at about 24 months and a second peak at almost 60 months. The same pattern was observed when the whole recurrence risk was split into the risk of local recurrence and the risk of distant metastasis. However, the hazard rate curves for both contralateral breast tumours and second primary tumours revealed a uniform course at an almost constant level. When patients with distant metastases were grouped by site of recurrence (soft tissue, bone, lung or liver or central nervous system), the corresponding hazard rate curves displayed the typical bimodal pattern with a first peak at about 24 months and a later peak at about 60 months.
The bimodal dynamics for early stage breast cancer recurrence is again confirmed, providing support to the proposed tumour-dormancy-based model. The recurrence dynamics does not depend on the site of metastasis indicating that the timing of recurrences is generated by factors influencing the metastatic development regardless of the seeded organ. This finding supports the view that the disease course after surgical removal of the primary tumour follows a common pathway with well-defined steps and that the recurrence risk pattern results from inherent features of the metastasis development process, which are apparently attributable to tumour cells.
乳腺癌复发和死亡的动态变化呈现双峰风险率模式，这已在各种数据库中得到证实。针对这一发现，人们提出了一些解释，假定每个峰值是由相似复发的聚集产生的，而不同峰值则源于不同类别的复发。
对意大利米兰国家癌症研究所接受保乳手术的1526例患者的复发动态进行了分析，记录了首次复发的部位。该研究聚焦于随访期间发生的首个临床相关事件（即局部复发、远处转移、对侧乳腺癌、第二原发肿瘤），通过估计特定风险率来研究其动态变化。
任何复发（包括局部和远处疾病复发）的风险率呈现双峰模式，第一个高峰在约24个月时达到峰值，第二个高峰在近60个月时出现。当将整个复发风险分为局部复发风险和远处转移风险时，观察到相同的模式。然而，对侧乳腺肿瘤和第二原发肿瘤的风险率曲线显示出在几乎恒定水平上的均匀变化过程。当远处转移患者按复发部位（软组织、骨、肺或肝或中枢神经系统）分组时，相应的风险率曲线呈现典型的双峰模式，第一个高峰在约24个月时出现，随后一个高峰在约60个月时出现。
早期乳腺癌复发的双峰动态变化再次得到证实，为所提出的基于肿瘤休眠的模型提供了支持。复发动态不依赖于转移部位，这表明复发时间是由影响转移发展的因素产生的，而与植入器官无关。这一发现支持了这样一种观点，即手术切除原发肿瘤后的疾病进程遵循一个具有明确步骤的共同途径，并且复发风险模式是由转移发展过程的固有特征导致的，这些特征显然归因于肿瘤细胞。
