Diastolic Dysfunction Occurs Early in HER2-Positive Breast Cancer Patients Treated Concurrently With Radiation Therapy and Trastuzumab.
BACKGROUND
Left ventricular ejection fraction (LVEF) is used routinely to monitor cardiac dysfunction associated with breast cancer treatment. In this study the prevalence of early left ventricular diastolic dysfunction (LVDD) and its relationship to the dose-volume of the heart irradiated were evaluated in HER2-positive breast cancer patients undergoing concurrent trastuzumab and adjuvant radiotherapy (RT).


METHODS
Data from 40 breast cancer patients treated with concurrent trastuzumab and left-sided adjuvant RT between September 2011 and October 2012 were collected prospectively. For comparison, 32 patients treated with concurrent trastuzumab and right-sided adjuvant RT and 71 patients treated with left-sided RT alone were collected retrospectively. Echocardiography was obtained before RT, immediately following RT, and 3 and 6 months after RT. Doses to the heart and left ventricle (LV) were quantified.


RESULTS
Prior to RT with concurrent trastuzumab, 11 of 29 (left) and 8 of 25 (right) patients with normal baseline left ventricular diastolic function (LVDF) developed LVDD. In patients receiving left-sided RT alone, 12 of 61 patients with normal baseline LVDF developed LVDD. Dmean, D15-D40, D60-D70, and V3-V10 of the LV were significantly higher in patients who developed LVDD after concurrent trastuzumab and left-sided RT. In contrast, only two patients developed grade 1 LVEF decrease after both concurrent treatment and left-sided RT alone.


CONCLUSIONS
Changes in LVDF compared with LVEF are more sensitive for early detection of cardiotoxicity. The dose-volume of the heart contributes significantly to the risk of LVDD in patients with left-sided breast cancer treated concurrently with trastuzumab.


CONCLUSIONS
Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose-volume of the heart irradiated in patients with left-sided breast cancer receiving radiotherapy concurrently with trastuzumab. This result highlights the importance of decreasing the dose-volume of heart irradiated as a protective strategy in the treatment setting of concurrent trastuzumab and radiotherapy. Diastolic dysfunction may serve as a more sensitive tool for the early detection of cardiac damage and should be incorporated as a routine parameter in the functional monitoring of cardiotoxicity.
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Lu
L
Cao
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Gang
G
Cai
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Cai
C
Chang
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Ai-Yu
AY
Miao
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Xiao-Li
XL
Yu
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Zhao-Zhi
ZZ
Yang
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Jin-Li
JL
Ma
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Qian
Q
Zhang
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Jiong
J
Wu
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Xiao-Mao
XM
Guo
Departments of Radiation Oncology, Ultrasound, and Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China chenjiayi0188@aliyun.com.
Jia-Yi
JY
Chen
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004452:Echocardiography; D005260:Female; D054144:Heart Failure, Diastolic / Q000139:chemically induced / Q000503:physiopathology*; D006801:Humans; D008875:Middle Aged; D011859:Radiography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects; D016277:Ventricular Function, Left / Q000187:drug effects
D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
Breast cancer; Concurrent treatment; Diastolic dysfunction; Radiotherapy; Trastuzumab