Fluctuation of the left ventricular ejection fraction in patients with HER2-positive early breast cancer treated by 12 months of adjuvant trastuzumab

The Breast ◽  
2018 ◽  
Vol 41 ◽  
pp. 1-7 ◽  
Author(s):  
Quentin Jacquinot ◽  
Sophie Paget-Bailly ◽  
Pierre Fumoleau ◽  
Gilles Romieu ◽  
Jean Yves Pierga ◽  
...  
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 509-509
Author(s):  
Pamela N. Munster ◽  
Roy Tamura ◽  
Jeffrey Krischer ◽  
Worta J. McCaskill-Stevens ◽  
Maya Guglin

509 Background: Treatment of HER2-positive breast cancer patients with trastuzumab is highly effective. However, a trastuzumab-associated decline in the left ventricular ejection fraction (LVEF) and clinical heart failure often prompt interruption and discontinuation of treatment. We therefore evaluated the preventive impact of an ACE inhibitor or beta blockers on the left ventricular ejection fraction (LVEF) during treatment of trastuzumab and chemotherapy. Methods: In a prospective randomized study, women with early stage HER2 positive breast cancer undergoing (neo)adjuvant chemotherapy with trastuzumab were randomized to receive either once daily lisinopril (10mg), carvedilol (10mg) or placebo during treatment with trastuzumab and further stratified by anthracycline use (AC+T versus nonAC+T). In a follow up to the initially presented primary endpoint of overall cardiotoxicity, we measured the protective effects of lisinopril or carvedilol to prevent a trastuzumab induced LVEF decrease to less than 50% over the course of therapy as well as the impact on LVEF decrease by >10% within normal LVEF levels. Results: A total of 468 women (mean age was 51±10.7 years) with HER2 overexpressing early-stage breast cancer from 127 community-based oncology practices were enrolled, a prespecified minimum target of 189 (40%) patients were treated with AC+T and 279 (60%) with nonAC+T. Baseline cardiac risk factors of this study population included obesity and an elevated blood pressure. Patients in the anthracycline group were younger and without hypertension. A small, not clinically relevant decrease in LVEF was observed during trastuzumab therapy in all patients which was not significantly altered by any of the cardiac interventions. The rate of LVEF decline to <50% was much more frequent in patients treated with an anthracycline than those with a non-anthracycline containing regimen (21% vs 4.1%). Treatment with lisinopril averted the decline in LVEF in the AC+T group compared to placebo (10.8% vs 30.5%, p=0.045). A smaller but not significant effect was seen by carvedilol. The incidence of cardiotoxicity manifesting as LVEF decrease by ≥10% within the normal range was similar in both AC+T and the nonAC+T arms, and not affected by either lisinopril or carvedilol. Conclusions: In patients treated with trastuzumab without anthracyclines, the impact of trastuzumab on LVEF is small and infrequent. In contrast, patients treated with anthracyclines prior to trastuzumab, demonstrated a decrease in LVEF to below normal levels in a larger than previously reported number of women in this community based setting. The trastuzumab-anthracycline induced decline in LVEF could be prevented with concurrent treatment with lisinopril, which was tolerable even in patients without hypertension. Clinical trial information: NCT01009918.


2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Fatemeh Zohrian ◽  
Azin Alizadehasl ◽  
Lida Zahedi ◽  
Homa Ghaderian ◽  
Robab Anbiaee ◽  
...  

Background: Human epidermal growth factor receptor 2(HER2) is a gene that makes proteins in the breast cell. The HER2 gene is present in about 25% - 30% of patients with breast cancers. The most common side effect of drugs is left ventricular dysfunction. Evaluation of left ventricular ejection fraction (LVEF) by 2D echocardiography cannot detect subtle changes in LV systolic function. Objectives: We want to draw a comparison between two groups of breast cancer patients (HER2 positive and negative) by advanced echocardiography. Methods: We have conducted a single center prospective study at Rajaie Cardiovascular Medical and Research Center in 2018 - 2019. Results: This analysis included 58 patients with breast cancer. 15 cases (34%) were HER2 positive. Mean left ventricular ejection fraction (2D LVEF) in HER2 positive patients was 55 % at baseline and in HER2 negative patients was 55 %. In HER2 positive patients we had 10 percent decrease in LVEF during follow-up and the final LVEF was about 45% (P value < 0.05). Mean left ventricular ejection fraction by 3D echocardiography (3D LVEF) in HER positive patients was 57 % and in HER2 negative patients was 55 % at baseline. In HER2 positive patients we had about 20% decrease in 3D LVEF and the final LVEF was 40 % (P value < 0.05). Mean circumferential strain (GCS) in HER2 positive patients was -21 and in HER2 negative patients was -21 at baseline which decreased to -18 in HER positive patients and -17 in HER2 negative patients, showing clinical significance ( P value = 0.008). Conclusions: In our study HER2 positive breast cancers showed about 10% drop in 2DEF, about 20% drop in 3DLVEF and about 5% drop in HMLVEF, which all were significant (P value < 0.05). We found that GCS is more sensitive than GLS in detecting subclinical involvement, and early changes in GCS is a good predictor of subsequent development of drugs (anthracycline-transtuzumab) induced cardiotoxicity.


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