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
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.
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.
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.
Digital Object Identifier (DOI)
Supported by Grants No. U10CA-180868, U10CA-180822, and UG1CA-189867 from the National Cancer Institute, Department of Health and Human Services, Public Health Service; the Breast Cancer Research Foundation (P.A.G.); Susan G. Komen for the Cure (E.P.M.); and Genentech.
Clinical trial information: NCT00004067
Disclosures provided by the authors are available with this article at jco.org.
Ganz, Patricia A.; Romond, Edward H.; Cecchini, Reena S.; Rastogi, Priya; Geyer, Charles E. Jr.; Swain, Sandra M.; Jeong, Jong-Hyeon; Fehrenbacher, Louis; Gross, Howard M.; Brufsky, Adam M.; Flynn, Patrick J.; Wahl, Tanya A.; Seay, Thomas E.; Wade, James L. III; Biggs, David D.; Atkins, James N.; Polikoff, Jonathan; Zapas, John L.; Mamounas, Eleftherios P.; and Wolmark, Norman, "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" (2017). Markey Cancer Center Faculty Publications. 102.