JCO：内分泌治疗特定的不良事件或预示乳腺癌患者较佳生存结局

与内分泌治疗疗效有关的因素可能包括，相关的特定不良事件(AE)以及对循环系统中雌激素进行的清除或阻断情况。在2013年4月22日在线出版的《临床肿瘤学杂志》(Journal of Clinical Oncology)上，荷兰莱顿大学Cornelis J.H. van de Velde博士等人针对参与“他莫昔芬-依西美坦辅助治疗国际联合(TEAM)试验”的绝经后乳腺癌患者，考察了特定AE(包括血管舒缩症状[VMS]、肌肉骨骼不良事件[MSAE]以及外阴阴道症状[VVS])与生存结局间的关系。
该研究中与疗效相关的主要终点为无病生存率(DFS)、总生存率(OS)以及远端转移(DM)情况。研究人员对在内分泌治疗后第一年时出现的VMS、MSAE及VVS情况进行了考量。研究排除了未展开原指定治疗方案的患者，以及/或在随机分配后1年内，出现事件(复发/死亡)的患者。最终通过界标分析以及时间依赖性Cox比例风险模型，对治疗起始至5年时的生存差异进行了评价。
该研究共包括9,325例患者。研究发现，出现特定AE的患者(v 非特定性或无AE)DFS及OS结局均好于未出现相关症状报告的患者(DFS多变量风险比 [HR]: VMS, 0.731 [95% CI, 0.618至0.866]; MSAE, 0.826 [95% CI, 0.694至0.982]; VVS, 0.769 [95% CI, 0.585至1.01]; OS多变量HR: VMS, 0.731 [95% CI, 0.618至0.866]; MSAE, 0.826 [95% CI, 0.694至0.982]; VVS, 0.769 [95% CI, 0.585至1.01]; OS 多变量HR: VMS, 0.583 [95% CI, 0.424至 0.803]; MSAE, 0.811 [95% CI, 0.654至1.005]; VVS, 0.570 [95% CI, 0.391至0.831]) 且DM情况较少(VMS, 0.813 [95% CI, 0.664至0.996]; MSAE, 0.749 [95% CI, 0.601至 0.934]; VVS, 0.687 [95% CI, 0.436至1.085])。此外，特定AE数量的增加也与较佳的生存结局有关。治疗方案分配与患者结局无关。
研究人员据此认为，对于接受内分泌治疗的乳腺癌患者，某些特定AE与较佳的生存结局有关，因此，该结论可能有助于对患者的治疗缓解情况进行预测。

Specific Adverse Events Predict Survival Benefit in Patients Treated With Tamoxifen or Aromatase Inhibitors: An International Tamoxifen Exemestane Adjuvant Multinational Trial Analysis.
PURPOSE
Specific adverse events (AEs) associated with endocrine therapy and related to depletion or blocking of circulating estrogens may be related to treatment efficacy. We investigated the relationship between survival outcomes and specific AEs including vasomotor symptoms (VMSs), musculoskeletal adverse events (MSAEs), and vulvovaginal symptoms (VVSs) in postmenopausal patients with breast cancer participating in the international Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.
PATIENTS AND METHODS
Primary efficacy end points were disease-free survival (DFS), overall survival (OS), and distant metastases (DM). VMSs, MSAEs, and VVSs arising in the first year of endocrine treatment were considered. Patients who did not start or who discontinued their allocated therapy and/or had an event (recurrence/death) within 1 year after randomization were excluded. Landmark analyses and time-dependent multivariate Cox proportional hazards models assessed survival differences up to 5 years from the start of treatment.
RESULTS:
VMSs, 0.731 [95% CI, 0.618 to 0.866]; MSAEs, 0.826 [95% CI, 0.694 to 0.982]; VVSs, 0.769 [95% CI, 0.585 to 1.01]; multivariate HR for OS: VMSs, 0.583 [95% CI, 0.424 to 0.803]; MSAEs, 0.811 [95% CI, 0.654 to 1.005]; VVSs, 0.570 [95% CI, 0.391 to 0.831]) and fewer DM (VMSs, 0.813 [95% CI, 0.664 to 0.996]; MSAEs, 0.749 [95% CI, 0.601 to 0.934]; VVSs, 0.687 [95% CI, 0.436 to 1.085]) than patients not reporting these symptoms. Increasing numbers of specific AEs were also associated with better survival outcomes. Outcomes were unrelated to treatment allocation.
CONCLUSION
Certain specific AEs are associated with superior survival outcomes and may therefore be useful in predicting treatment responses in patients with breast cancer treated with endocrine therapy.