Department of Epidemiology, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
Oncologist. 2013;18(7):795-801. doi: 10.1634/theoncologist.2013-0065. Epub 2013 Jul 3.
Concerns have been raised about the cardiac safety profile of trastuzumab for the adjuvant treatment of early stage breast cancer in clinical practice. We assessed trastuzumab-related cardiotoxicity and its predictors in a large cohort of Italian women.
Through a record linkage between four regional health care databases, we identified the rate of severe cardiac adverse events among women treated with trastuzumab for early breast cancer in Lombardy. The cumulative risk of cardiotoxicity was estimated using the Kaplan-Meier method, and independent predictors were assessed using the Cox model.
Of 2,046 trastuzumab users, 53 (2.6%) experienced at least one hospitalization for a cardiac event, and there were two cardiac deaths. The cumulative risk of cardiotoxicity increased up to 2 years after starting treatment, reaching a plateau at 2.8%. The risk was low (0.2%) among young women, whereas the incidence was approximately 10% in women aged ≥70 years, irrespective of cardiovascular risk factors. Age and history of cardiac disease were strong predictors of cardiotoxicity, with a hazard ratio of 11.3 (95% confidence interval [CI]: 3.5-36.6) for women aged ≥70 years as compared with those <50 years of age. Hazard ratio was 4.4 (95% CI: 2.1-9.5) for women with a history of cardiac disease compared with those without a history of cardiac disease.
Cardiotoxicity of trastuzumab varies considerably across subgroups of patients. The long-term safety profile was less favorable than in the largest clinical trial. Strategies to reduce cardiotoxicity in high-risk women should be investigated.
在临床实践中，曲妥珠单抗用于早期乳腺癌辅助治疗的心脏安全性受到关注。我们评估了意大利女性大队列中曲妥珠单抗相关的心脏毒性及其预测因素。
通过四个区域卫生保健数据库的记录链接，我们确定了在伦巴第接受曲妥珠单抗治疗早期乳腺癌的女性中严重心脏不良事件的发生率。使用 Kaplan-Meier 方法估计心脏毒性的累积风险，并使用 Cox 模型评估独立预测因素。
在 2046 名曲妥珠单抗使用者中，有 53 名（2.6%）至少因心脏事件住院一次，并有 2 例心脏死亡。心脏毒性的累积风险在治疗开始后 2 年内增加，达到 2.8%的平台。年轻女性的风险较低（0.2%），而≥70 岁的女性风险约为 10%，无论心血管危险因素如何。年龄和心脏病史是心脏毒性的强烈预测因素，≥70 岁的女性与<50 岁的女性相比，风险比为 11.3（95%置信区间[CI]：3.5-36.6）。与无心脏病史的女性相比，有心脏病史的女性的风险比为 4.4（95% CI：2.1-9.5）。
曲妥珠单抗的心脏毒性在不同患者亚组中差异很大。长期安全性不如最大的临床试验。应研究减少高危女性心脏毒性的策略。
