Affiliations of authors: Department of Surgical Oncology (WvdW, MK, EB, CJHvdV, GJL), Department of Gerontology and Geriatrics (WvdW, MK, EB, RGJW, AJMdC), and Department of Medical Oncology (JWRN), Leiden University Medical Center, Leiden, the Netherlands; Department of Research, Comprehensive Cancer Centre the Netherlands, Utrecht, the Netherlands (SS); Department of Health Technology and Services Research, University of Twente, Enschede, the Netherlands (SS); Department of Medical Oncology, Erasmus MC-Daniel Den Hoed Cancer Center, Rotterdam, the Netherlands (CS).
J Natl Cancer Inst. 2014 Apr;106(4):dju051. doi: 10.1093/jnci/dju051. Epub 2014 Mar 19.
Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancer patients.
We compared characteristics and outcomes of breast cancer patients (n = 1325) who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor-positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65-74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided.
Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P < .001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95% CI = 0.55 to 0.95; P = .02) than patients in the general population.
Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial.
试验的纳入是有选择性的，因此结果可能不适用于一般人群。本研究旨在调查老年乳腺癌患者随机临床试验结果的外部有效性。
我们比较了参加随机临床试验（三苯氧胺依西美坦辅助多国试验）的老年乳腺癌患者（n = 1325）和相应年龄的一般人群中未经选择的乳腺癌患者（n = 1056）的特征和结局。荷兰诊断为激素受体阳性乳腺癌且无远处转移的年龄≥65 岁的患者，淋巴结受累、肿瘤大于 3cm 或组织学分级为 3 级的 1-3cm 肿瘤患者，完成局部治疗后纳入研究。按年龄（65-74 岁；≥75 岁）分层分析。主要结局为总死亡率。多变量 Cox 比例风险模型用于评估协变量与总死亡率之间的关系。所有统计检验均为双侧检验。
无论年龄大小，参加试验的患者合并症较少、社会经济地位较高、肿瘤较小（均 P <.001）。在 65-74 岁的患者中，参加试验的患者与一般人群的总死亡率相似（多变量风险比[HR] = 1.08；95%置信区间[CI] = 0.73 至 1.60）。相反，在 75 岁或以上的患者中，参加试验的患者总死亡率较低（多变量 HR = 0.72；95%CI = 0.55 至 0.95；P =.02），而一般人群的总死亡率较高。
75 岁或以上的乳腺癌试验参与者不能代表一般人群中相应年龄的老年乳腺癌患者，这会影响试验的外部有效性。
