PDF(Pubmed)
Abstract：
Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies-tamoxifen and trastuzumab-on recurrence using the trend-in-trend pharmacoepidemiologic study design.
We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007.
For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4).
We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach.
We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007.
For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4).
We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach.
摘要：
目的：乳腺癌的平均10年相对生存率达到84%。这种有利的生存是应该的，在某种程度上,引入生物标志物指导疗法。我们使用趋势-趋势药物流行病学研究设计评估了引入两种辅助疗法-他莫昔芬和曲妥珠单抗对复发的人群水平影响。
方法：我们确定了丹麦乳腺癌组临床数据库中登记的非转移性乳腺癌女性的数据。我们使用趋势-趋势设计来估计（1）他莫昔芬用于1982年绝经后雌激素受体（ER）阳性乳腺癌妇女，（2）他莫昔芬用于1999年诊断为ER阳性乳腺癌的绝经前妇女，以及（3）曲妥珠单抗用于2007年诊断为人类表皮生长因子受体2阳性乳腺癌的60岁以下妇女的人群水平效果。
结果：对于1999年诊断为ER阳性乳腺癌的绝经前妇女中引入他莫昔芬的人群水平影响，复发风险降低了近一半（OR=0.52），与临床试验的证据一致；然而，估计值不精确(95%置信区间[CI]=0.25,1.85).从1982年开始，我们观察到他莫昔芬的使用与复发之间存在不精确的关联（OR=1.2495％CI=0.46，5.11），与临床试验的先验知识不一致。对于2007年引入曲妥珠单抗，估计也与试验证据一致，虽然不精确(OR=0.51；95%CI=0.21，22.4)。
结论：我们证明了新的药物流行病学分析设计如何在基于人群的环境中用于评估常规临床护理和治疗进展的有效性，同时考虑了该方法的一些局限性。
方法：我们确定了丹麦乳腺癌组临床数据库中登记的非转移性乳腺癌女性的数据。我们使用趋势-趋势设计来估计（1）他莫昔芬用于1982年绝经后雌激素受体（ER）阳性乳腺癌妇女，（2）他莫昔芬用于1999年诊断为ER阳性乳腺癌的绝经前妇女，以及（3）曲妥珠单抗用于2007年诊断为人类表皮生长因子受体2阳性乳腺癌的60岁以下妇女的人群水平效果。
结果：对于1999年诊断为ER阳性乳腺癌的绝经前妇女中引入他莫昔芬的人群水平影响，复发风险降低了近一半（OR=0.52），与临床试验的证据一致；然而，估计值不精确(95%置信区间[CI]=0.25,1.85).从1982年开始，我们观察到他莫昔芬的使用与复发之间存在不精确的关联（OR=1.2495％CI=0.46，5.11），与临床试验的先验知识不一致。对于2007年引入曲妥珠单抗，估计也与试验证据一致，虽然不精确(OR=0.51；95%CI=0.21，22.4)。
结论：我们证明了新的药物流行病学分析设计如何在基于人群的环境中用于评估常规临床护理和治疗进展的有效性，同时考虑了该方法的一些局限性。
