原创SIBCS12-11 01:10


  既往研究发现,对于淋巴结阳性且HER2过表达早期乳腺癌患者,术后辅助化疗+曲妥珠单抗与单用辅助化疗相比,10年总生存率为84%比75%,死亡风险减少约37%,但是不良反应之一为治疗早期发生的心脏毒性,严重心脏事件7年累计发生率为4.0%比1.3%,其中绝大多数发生于曲妥珠单抗首次用药2年内,仅2例充血性心力衰竭发生于曲妥珠单抗首次用药2年后。然而,对于辅助治疗完成之后长期随访无癌患者,缺乏心脏功能和健康相关生活质量的客观数据。


  2017年10月26日,美国临床肿瘤学会《临床肿瘤学杂志》在线发表NSABP/NRG-B31随机对照研究报告,对术后接受多柔比星+环磷酰胺→紫杉醇±曲妥珠单抗(AC→P或AC→PH)辅助治疗的淋巴结阳性且HER2过表达早期乳腺癌患者,进行了心脏功能和生活质量的长期随访。



  该研究对淋巴结阳性且HER2过表达早期乳腺癌术后接受多柔比星+环磷酰胺→紫杉醇(AC→P,对照组)或多柔比星+环磷酰胺→紫杉醇+曲妥珠单抗(AC→PH,曲妥珠单抗组)辅助治疗的无病生存患者进行长期随访,通过多导联捕获扫描(多导联心电图结合同位素心血管动态造影)测量左室射血分数,并根据杜克体力状态指数、医疗结局研究问卷、目前用药和共病情况回顾,由患者报告健康相关生活质量结局。该研究在美国政府临床研究注册登记网站的编号为:NCT00004067。


  结果,NSABP/NRG-B31研究入组患者共2110例(对照组1061例、曲妥珠单抗组1058例),其中:


  经过中位随访8.8年,对照组与曲妥珠单抗组相比,左室射血分数绝对值<50%、相对用药前减少≥10%的患者比例相似,分别为5/110例(4.5%)、10/297例(3.4%)。


  杜克体力状态指数评分较低的相关因素包括年龄、用药(高血压、心脏病、糖尿病、高血脂),但是不包括患者是否接受曲妥珠单抗。


  因此,对于原无心脏疾病的淋巴结阳性且HER2过表达早期乳腺癌患者,蒽环类+氮芥类序贯紫杉类辅助化疗加入曲妥珠单抗,不会导致心脏功能、心脏症状或健康相关生活质量的长期恶化。杜克体力状态指数问卷可能提供简单有效的工具,用于监测患者报告的变化,以反映心脏功能。


J Clin Oncol. 2017 Oct 26. [Epub ahead of print]


Long-Term Follow-Up of Cardiac Function and Quality of Life for Patients in NSABP Protocol B-31/NRG Oncology: A Randomized Trial Comparing the Safety and Efficacy of Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel With AC Followed by Paclitaxel and Trastuzumab in Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2.


Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N.


National Surgical Adjuvant Breast and Bowel Project/NRG Oncology; University of Pittsburgh; Magee-Womens Hospital; Allegheny Health Network Cancer Institute, Pittsburgh, PA; University of California at Los Angeles, Los Angeles; Kaiser Permanente, Vallejo; Kaiser Permanente, San Marco, CA; University of Kentucky, Lexington, KY; Virginia Commonwealth University, Richmond, VA; MedStar Washington Hospital Center, Washington, DC; Dayton National Cancer Institute Community Oncology Research Program (NCORP), Dayton, OH; Metro-Minnesota Community Clinical Oncology Program (CCOP), Woodbury, MN; Fred Hutchinson Cancer Research Center, Seattle, WA; Atlanta Regional CCOP, Atlanta, GA; Heartland NCORP, Decatur, IL; Christiana Care Health System, Newark, DE; Southeast Clinical Oncology Research Consortium NCORP, Goldsboro, NC; Orlando Health, Orlando, FL.


PURPOSE: Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment.


PATIENTS AND METHODS: Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2-positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported outcomes using the Duke Activity Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions.


RESULTS: At a median follow-up of 8.8 years among eligible participants, five (4.5%) of 110 in the control group and 10 (3.4%) of 297 in the trastuzumab group had a > 10% decline in left ventricular ejection fraction from baseline to a value < 50%. Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab.


CONCLUSION: In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function.


PMID: 29072977


DOI: 10.1200/JCO.2017.74.1165