Cardiotoxicity of radiotherapy, chemotherapy, and dual anti-HER2 therapy in HER2-positive breast cancer patients from Saudi Arabia

Introduction: Treatment with anti-human epidermal growth factor receptors 2 (HER2) therapy can cause cardiac dysfunction (CD). The effect of loco-regional radiotherapy (XRT) dose-volume parameters and the companion chemotherapy (CT) regimen on developing CD in breast cancer (BC) patients is controversial. The impact of these variables in developing CD among patients with HER2-positive BC, receiving CT plus anti-HER2 monoclonal antibodies (MoAb) was evaluated in routine clinical practice. Methods: A retrospective chart review of patients with HER2-positive BC between 2015 and 2019 was conducted. The following data were collected: demographics, body mass index (BMI), body surface area (BSA), pathology/laterality/stage of the tumor, CT settings and regimens, Ejection fraction (EF%) at baseline and at different time points (3, 6, 9, 12, 15 and 18 months), comorbidities including cardiac diseases, smoking and medications, XRT (mean heart dose and heart V25), breast surgery type, application of single versus dual anti-HER2 MoAb, and the number of cycles. CD is defined as a drop in (EF%) of at least 10 percentage points from baseline and/or below 50% at any point of the time during follow-up. Univariate and multivariate analysis was used to assess the association of CD and various variables with a significance level of <0.05. Results: A total of 224 female patients was eligible for analysis with a mean age at diagnosis of 51 ± 12, BMI 29.6 ± 6.4, BSA 1.74 ± 0.19, 53% with left BC, 63% had nonmetastatic BC, 52% with comorbidities (DM, systemic hypertension, and dyslipidemia), medication use in 48% with metformin being the most commonly used (15%) and beta-blockers (5%), 9.4% smoker, 11% had prior ischemic heart diseases, 70% had a mastectomy, 18% lumpectomy and 12% no surgery, 58% received loco-regional XRT. The cumulative incidence of CD was (33%) during the follow-up period, noting that the first and subsequent drops of EF at any point of time during the follow-up were counted as a new event even for the same patient. Although XRT and CT regimen showed a significant association on univariate analysis, this association did not translate into significance in multivariate analysis with a P = 0.198 and 0.326, respectively. Conclusion: XRT mean heart dose and V25 of the heart, anthracycline-based CT did not influence the risk of developing CD among this cohort. Likewise, the dual anti-HER2 therapy with trastuzumab and pertuzumab and the number of trastuzumab cycles were not significant factors in increasing CD. It is reassuring to demonstrate the safety of these approaches in real-life clinical practice.