Hölzel Dieter, Eckel Renate, Bauerfeind Ingo, Baier Bernd, Beck Thomas, Braun Michael, Ettl Johannes, Hamann Ulrich, Kiechle Marion, Mahner Sven, Schindlbeck Christian, de Waal Johann, Harbeck Nadia, Engel Jutta
Munich Cancer Registry (MCR) of the Munich Tumour Centre (TZM), Institute for Medical Information Processing, Biometry and Epidemiology (IBE), University Hospital of Munich, Ludwig-Maximilians-University (LMU), Tumorregister München, Klinikum Großhadern/IBE, 81377, Munich, Germany.
Head of the Breast Cancer Project Group of the Munich Tumour Centre (TZM) and of Department of Obstetrics and Gynaecology, Klinikum Landshut, Landshut, Germany.
J Cancer Res Clin Oncol. 2017 Sep;143(9):1701-1712. doi: 10.1007/s00432-017-2428-0. Epub 2017 Apr 20.
Systemic therapies (ATHs) in early breast cancer have improved the survival of breast cancer (BC) patients in recent decades. The magnitude of the changes in overall, metastasis-free (MFS) and post-metastatic (PMS) survival and in the metastasis (MET) pattern will be described.
We analysed 60,227 patients with a diagnosis of T-N-M0 BC between 1978 and 2013 and 11,983 patients with metastases (MET) in the Munich Cancer Registry. Patients will be divided into four time periods to identify relationships between BC and METs. Survival was estimated using Kaplan-Meier curves, and Cox proportional hazards models were used to explore the impact of the BC subtype and MET status on survival with the time periods as surrogate markers for ATH evolution.
During the observation period, 5-year relative survival has improved from 80.3 to 93.6% with an adjusted hazard ratio of 0.54 (P < 0.0001). Successful implementation of ATH has changed the MET pattern. The percentage of liver and CNS METs has more than doubled, the rate of lung METs remains stable, and the rate of bone METs has been reduced by approximately 50%. MFS has been prolonged with a hazard ratio 0.75 (P < 0.0001), but PMS has declined (hazard ratio 1.36; P < 0.0001); however, effects of adjuvant and palliative treatments cannot be separated. These results do not contradict improvements in advanced BC and do not suggest alterations of MET tumour biology by ATH.
Over the past three decades, ATHs have dramatically improved patient survival after BC diagnosis-most likely, by eradicating prevalent micro-METs; as a result, the MET pattern has changed. Eradicating only a portion of the first METs results in delaying the onset of subsequent MET, which leads to an apparently paradoxical effect: an extension of the MET-free interval and a reduction in PMS.
近几十年来，早期乳腺癌的全身治疗（ATHs）提高了乳腺癌（BC）患者的生存率。本文将描述总体生存率、无转移生存率（MFS）和转移后生存率（PMS）以及转移（MET）模式的变化幅度。
我们分析了慕尼黑癌症登记处1978年至2013年间诊断为T-N-M0 BC的60227例患者以及11983例有转移（MET）的患者。患者将被分为四个时间段，以确定BC与MET之间的关系。使用Kaplan-Meier曲线估计生存率，并使用Cox比例风险模型以时间段作为ATH演变的替代标志物，探讨BC亚型和MET状态对生存率的影响。
在观察期内，5年相对生存率从80.3%提高到93.6%，调整后的风险比为0.54（P<0.0001）。ATH的成功实施改变了MET模式。肝脏和中枢神经系统MET的百分比增加了一倍多，肺部MET的发生率保持稳定，骨MET的发生率降低了约50%。MFS延长，风险比为0.75（P<0.0001），但PMS下降（风险比1.36；P<0.0001）；然而，辅助治疗和姑息治疗的效果无法区分。这些结果与晚期BC的改善并不矛盾，也不表明ATH会改变MET肿瘤生物学。
在过去三十年中，ATHs显著提高了BC诊断后的患者生存率——很可能是通过根除普遍存在的微小MET；因此，MET模式发生了变化。仅根除一部分首次出现的MET会导致后续MET的发生延迟，这会产生一个明显矛盾的效果：无转移间隔期延长和PMS降低。
