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

Jacquinot, Quentin; Paget‐Bailly, Sophie; Fumoleau, P.; Romieu, Gilles; Pierga, Jean Yves; Espié, Marc; Lortholary, Alain; Nabholtz, J.-M.; Mercier, C.; Pauporté, Iris; Henriques, Julie; Pivot, Xavier

doi:10.1016/j.breast.2018.06.001

Cited by 10 publications

(8 citation statements)

References 35 publications

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“…Our finding that LVEF after trastuzumab treatment is significantly lower than at the baseline is consistent with the long-term data of the PHARE trial, investigating one year vs. 6 months of adjuvant trastuzumab treatment [11]. At a 30-months follow-up cutoff, LVEF mean values, that had declined by 3.6% at the end of trastuzumab treatment, compared with baseline values, tended to recover, but for almost a half of the patients, LVEF recovery was only partial.…”

Section: Discussionsupporting

confidence: 90%

Treatment with Beta-Blockers and ACE-Inhibitors in Breast Cancer Patients Receiving Adjuvant Trastuzumab-Based Therapy and Developing Mild Cardiac Toxicity: A Prospective Study

Geuna

Lombardi

Martinello

et al. 2020

Cancers

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Background: Angiotensin Converting Enzyme inhibitors (ACEis) and beta-blockers (BB) are suggested to prevent and treat trastuzumab-related cardiac toxicity. We performed a prospective clinical trial in women experiencing mild cardiac toxicity (MCT) while on adjuvant treatment with trastuzumab. Methods: MCT was defined as an asymptomatic absolute decrease in LVEF of ≥ 10 percentage units to >50%. Treatment consisted of enalapril 2.5 mg bid and carvedilol 3.75 mg bid, which were up-titrated to 10 mg bid for the enalapril and 6.25 mg bid of carvedilol. In patients receiving study drug, the primary study end-point was LVEF recovery, which was defined as a post-trastuzumab LVEF returning to no less than −5 percentage points of the baseline value. Results: 103 patients were enrolled, 100 started trastuzumab, and 98 completed the planned treatment. Sixteen patients (16%) had MCT and received study drugs until trastuzumab completion. None of these patients achieved a post-trastuzumab LVEF recovery. Nevertheless, treated patients had significantly higher median LVEF recovery from nadir to post-trastuzumab LVEF in (8% points vs. 4% points, respectively, p = 0.004), resulting in no difference in post-treatment LVEF values compared to patients without MCT. Conclusion: Treatment of MCT with ACEis and BB allows faster LVEF recovery from nadir values and should be further studied in this setting.

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Section: Discussionsupporting

confidence: 90%

Treatment with Beta-Blockers and ACE-Inhibitors in Breast Cancer Patients Receiving Adjuvant Trastuzumab-Based Therapy and Developing Mild Cardiac Toxicity: A Prospective Study

Geuna

Lombardi

Martinello

et al. 2020

Cancers

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“…These latter had completed surgery, chemotherapy and radiotherapy and were approximately 6 months from the beginning of treatment with trastuzumab. Similar data were found in the PHARE study (57) in which baseline LVEF was 66%. However, in that study, LVEF gradually decreased by 3.6% to reach a nadir at 12 months, in the absence of a physical exercise program (57).…”

Section: Discussionsupporting

confidence: 87%

Cardiotoxicity is mitigated after a supervised exercise program in HER2-positive breast cancer undergoing adjuvant trastuzumab

Jacquinot

Meneveau

Falcoz

et al. 2022

Front. Cardiovasc. Med.

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BackgroundTrastuzumab is used, alone or in conjunction with standard chemotherapy, to treat HER2-positive breast cancer (BC). Although it improves cancer outcomes, trastuzumab. can lead to cardiotoxicity. Physical exercise is a safe and effective supportive therapy in the management of side effects, but the cardioprotective effects of exercise are still unclear.ObjectivesThe primary aim of this study was to test whether trastuzumab-induced cardiotoxicity [left ventricular ejection fraction (LVEF) under 50%, or an absolute drop in LVEF of 10%] was reduced after a supervised exercise program of 3 months in patients with HER2-positive breast cancer. Secondary endpoints were to evaluate (i) cardiotoxicity rates using other criteria, (ii) cardiac parameters, (iii) cardiorespiratory fitness and (iv) whether a change in LVEF influences the cardiorespiratory fitness.Methods89 women were randomized to receive adjuvant trastuzumab in combination with a training program (training group: TG; n = 46) or trastuzumab alone (control group: CG; n = 43). The primary and secondary endpoints were evaluated at the end of the supervised exercise program of 3 months (T3).ResultsAfter exercise program, 90.5 % of TG patients and 81.8% of CG patients did not exhibit cardiotoxicity. Furthermore, whatever the used criterion, percentage of patients without cardiotoxicity were greater in TG (97.6 and 100% respectively) than in CG (90.9 and 93.9% respectively). LVEF and GLS values remained stable in both groups without any difference between the groups. In contrast, at T3, peak VO2 (+2.6 mL.min−1.kg−1; 95%CI, 1.8 to 3.4) and maximal power (+21.3 W; 95%CI, 17.3 to 25.3) increased significantly in TG, whereas they were unchanged in CG (peak VO2: +0.2 mL.min−1.kg−1; 95%CI, −0.5 to 0.9 and maximal power: +0.7 W, 95%CI, −3.6 to 5.1) compared to values measured at T0. No correlation between LVEF changes and peak VO2 or maximal power was observed.ConclusionA 12-week supervised exercise regimen was safe and improved the cardiopulmonary fitness in particular peak VO2, in HER2-positive BC patients treated with adjuvant trastuzumab therapy. The study is under powered to come to any conclusion regarding the effect on cardiotoxicity.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT02433067.

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“…Although after 2 weeks of suspension of treatment with vincristine, not all the tissue parameters have been recovered at the vascular level, complete normalization may be achieved after a longer period of suspension. Other authors have described the reversible partial effect in cardiac toxicity induced by trastuzumab ( Jacquinot et al, 2018 ) or toxicity induced by doxorubicin ( Zhou et al, 2018 ) after suspension of the treatment. However, the present study is the first that describes this aspect with vincristine.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Toxicity Induced by Chronic Vincristine Treatment

Herradón

González

et al. 2021

Front. Pharmacol.

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Vincristine is an effective anticancer agent for treating leukemias, lymphomas, and other solid tumors. Vincristine’s better-known severe side effects include bone marrow depression, hyponatremia, peripheral neuropathy, and gastrointestinal distress. In recent years, cardiovascular damage also has been described during vincristine treatments. However, the vascular toxicity induced by vincristine is little studied. The aim of the present is to evaluate whether these alterations remain after the suspension of chemotherapy treatment (sequelae) and the possible mechanisms involved in this vascular damage. Adult male Wistar rats were used. The animals were divided into four treatment groups: two groups of saline (0.9% NaCl; saline, sequelae saline) and two groups of vincristine (100 μg/kg; vincristine, sequelae vincristine). Saline or vincristine was administered intraperitoneally in two cycles of 5 days each, leaving a rest period between cycles of 2 days. The final cumulative vincristine dose administered was 1 mg/kg. Sequelae groups correspond to 2 weeks after stopping treatment with the antitumor agent. At the end of the different experimental protocols, cardiac and vascular functions were analyzed. Alterations in the expression of different proteins in the cardiovascular tissues were also investigated. Chronic treatment with vincristine did not produce significant changes in basal cardiac function but provoked significant endothelial dysfunction in the aorta and a significant decrease in the mesenteric contractile function. These cardiovascular functional alterations disappeared 2 weeks after the suspension of chemotherapy treatment. Vincristine treatment caused a significant increase in the expression of tumor necrosis factor-alpha (TNFα), endothelial and inducible nitric oxide synthases (eNOS and iNOS), and connexin 43 in cardiac tissue. In the aorta, the chronic treatment with vincristine caused a slight non-significant increase in TNFα expression, a significant increase in eNOS and iNOS, and a significant decrease in connexin 43. After 2 weeks of vincristine treatment (sequelae group), the expression of TNFα increased and eNOS and iNOS expressions disappeared, but a significant decrease in the expression of connexin 43 was still observed in the aorta. In mesenteric arteries, similar data to those found in the aorta were observed. In conclusion, chronic treatment with vincristine causes functional alterations in the vascular function of both conductance and resistance vessels and changes in the expressions of TNFα, eNOS, iNOS, and connexin 43 in cardiovascular tissues, implicating direct toxicity during its treatment. These functional alterations are transitory and disappear after the suspension of its treatment.

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

Cited by 10 publications

References 35 publications

Treatment with Beta-Blockers and ACE-Inhibitors in Breast Cancer Patients Receiving Adjuvant Trastuzumab-Based Therapy and Developing Mild Cardiac Toxicity: A Prospective Study

Treatment with Beta-Blockers and ACE-Inhibitors in Breast Cancer Patients Receiving Adjuvant Trastuzumab-Based Therapy and Developing Mild Cardiac Toxicity: A Prospective Study

Cardiotoxicity is mitigated after a supervised exercise program in HER2-positive breast cancer undergoing adjuvant trastuzumab

Cardiovascular Toxicity Induced by Chronic Vincristine Treatment

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