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. 2022 Sep 23:9:1000846.
doi: 10.3389/fcvm.2022.1000846. eCollection 2022.

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

Quentin Jacquinot  1   2 , Nathalie Meneveau  3 , Antoine Falcoz  4 , Malika Bouhaddi  2   5 , Pauline Roux  5 , Bruno Degano  6 , Marion Chatot  7 , Elsa Curtit  3   8 , Laura Mansi  3   8 , Marie-Justine Paillard  3 , Fernando Bazan  3 , Loïc Chaigneau  3 , Erion Dobi  3 , Guillaume Meynard  3 , Dewi Vernerey  4 , Xavier Pivot  9 , Fabienne Mougin  2   10
Affiliations

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

Quentin Jacquinot et al. Front Cardiovasc Med. .

Abstract

Background: Trastuzumab 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.

Objectives: The 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.

Methods: 89 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).

Results: After 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.

Conclusion: A 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 registration: www.ClinicalTrials.gov, identifier: NCT02433067.

Keywords: HER2 overexpression; breast cancer; cardiotoxicity; prevention; supervised exercise program; supportive care.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The study flow chart.
Figure 2
Figure 2
Violin plot for evolution of LVEF in TG (A) and CG (B).
Figure 3
Figure 3
Violin plot for evolution peak VO2 in TG (A) and CG (B).
Figure 4
Figure 4
Violin plot for evolution of maximal power in TG (A) and CG (B).
See this image and copyright information in PMC

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