Demicheli R, Retsky M W, Swartzendruber D E, Bonadonna G
Division of Medical Oncology, Istituto Nazionale Tumori, Milan, Italy.
Ann Oncol. 1997 Nov;8(11):1075-80. doi: 10.1023/a:1008263116022.
The commonly accepted theory of breast cancer metastatic development assumes continuous tumor growth from tumor seeding until documentation of clinical recurrence. In particular, Gompertzian growth kinetics is currently the theoretical cornerstone of the natural history of breast cancer, and has been widely utilized for planning treatments.
To verify agreement between findings and the implications of the continuous growth model, several published papers about the natural history of breast cancer after removal of the primary tumor were reviewed. Also, findings from animal models concerning metastasis biology were considered.
The continuous growth model failed in important ways upon this critical reappraisal. As an alternative, the tumor dormancy hypothesis was considered to provide a more reasonable description of tumor recurrence. Moreover, primary tumor removal was revealed as a potentially perturbing factor for metastasis development.
A new general outline of metastatic development of breast cancer incorporating tumor dormancy in specific micrometastatic phases, stochastic transitions between them, and start signals from surgery for micrometastatic growth was designed. The proposed model suggests new views concerning scheduling of current chemotherapy, new treatment approaches aimed at keeping micrometastases in a dormant state for the patient's entire life, and the careful reappraisal of the timing of surgery within the multimodal treatment of operable breast cancer.
乳腺癌转移发展的普遍接受理论认为，从肿瘤播散到临床复发记录期间肿瘤持续生长。特别是，戈姆珀茨生长动力学目前是乳腺癌自然史的理论基石，并已广泛用于治疗方案规划。
为验证研究结果与持续生长模型的含义之间的一致性，回顾了几篇关于原发性肿瘤切除后乳腺癌自然史的已发表论文。此外，还考虑了动物模型中有关转移生物学的研究结果。
在这次关键的重新评估中，持续生长模型在重要方面未能成立。作为替代方案，肿瘤休眠假说被认为能更合理地描述肿瘤复发。此外，原发性肿瘤切除被揭示为转移发展的一个潜在干扰因素。
设计了一个新的乳腺癌转移发展总体框架，该框架纳入了特定微转移阶段的肿瘤休眠、它们之间的随机转变以及手术引发微转移生长的启动信号。所提出的模型为当前化疗的时间安排、旨在使微转移在患者一生中保持休眠状态的新治疗方法以及对可手术乳腺癌多模式治疗中手术时机的审慎重新评估提出了新观点。
