School of Cancer & Pharmaceutical Sciences, King's College London, Great Maze Pond, London, SE1 9RT, United Kingdom; Guy's and St Thomas NHS Foundation Trust, Great Maze Pond, London, SE1 9RT, United Kingdom.
School of Cancer & Pharmaceutical Sciences, King's College London, Great Maze Pond, London, SE1 9RT, United Kingdom.
Breast. 2020 Apr;50:39-48. doi: 10.1016/j.breast.2020.01.006. Epub 2020 Jan 14.
Major advances in breast cancer treatment have led to a reducuction in mortality. However, there are still women who are not cured. We hypothesize there is a sub-group of women with treatment-resistant cancers causing early death.
Between 1975 and 2006, 5392 women with invasive breast cancer underwent surgery at Guy's Hospital, London. Data on patient demographics, tumour characteristics, treatment regimens, local recurrence, secondary metastasis, and death were prospectively recorded. We considered four time periods (1975-1982, 1983-1990, 1991-1998, 1999-2006). Risks and time to event analysis were performed with Cox proportional hazards model and Kaplan-Meier estimation.
Unadjusted hazard ratios for developing metastasis and overall mortality relative to the 1975-1982 cohort decreased steadily to 0.23 and 0.63, respectively in 1999-2006. However, metastasis-free interval shortened, with the proportion of women developing metastasis ≤5 years increasing from 73.9% to 83.0%. Furthermore, median post-metastatic survival decreased from 1.49 years to 0.94 years. Applying our risk criteria identified the presence of ±200 patients in each cohort who developed metastasis early and died within a much shorter time frame.
Advances in treatment have decreased the risk of metastasis and improved survival in women with invasive breast cancer over the last 40 years. Despite this, a subpopulation with shorter metastasis-free and post-metastatic survival who are unresponsive to available treatment remains. This may be due to the ATRESS phenomenon (adjuvant therapy-related shortening of survival) secondary to preselection inherent in adjuvant therapy, successful treatment of less malignant tumour cells and treatment-induced resistance in the remaining tumour clones.
乳腺癌治疗的重大进展已经降低了死亡率。然而，仍有一些女性未能治愈。我们假设存在一个治疗抵抗性癌症亚组，导致早期死亡。
1975 年至 2006 年间，5392 名浸润性乳腺癌女性在伦敦盖伊医院接受了手术。前瞻性记录了患者人口统计学、肿瘤特征、治疗方案、局部复发、继发转移和死亡的数据。我们考虑了四个时间段（1975-1982 年、1983-1990 年、1991-1998 年、1999-2006 年）。使用 Cox 比例风险模型和 Kaplan-Meier 估计进行风险和时间事件分析。
与 1975-1982 年队列相比，1999-2006 年发展转移和总死亡率的未调整危险比分别稳定下降至 0.23 和 0.63。然而，无转移间隔缩短，发展转移的女性比例在 5 年内从 73.9%增加到 83.0%。此外，转移后中位生存时间从 1.49 年缩短至 0.94 年。应用我们的风险标准，在每个队列中确定了存在±200 名患者，这些患者早期发生转移，在更短的时间内死亡。
在过去的 40 年中，治疗的进展降低了浸润性乳腺癌女性转移的风险并提高了生存率。尽管如此，仍然存在一小部分无转移和转移后生存时间较短、对现有治疗无反应的患者。这可能是由于辅助治疗相关的生存缩短（ATRESS 现象）所致，这是辅助治疗中固有的预选导致的，成功治疗了较少恶性肿瘤细胞，以及剩余肿瘤克隆中的治疗诱导耐药性所致。
