The effect of breast radiotherapy parameters (XRT), chemotherapy regimens (CT) and dual anti-HER2 monoclonal antibodies (MoAb) on the development of cardiac dysfunction (CD) among patients with HER2-positive breast cancer from Saudi Arabia.

person Atlal M. Abusanad Faculty of medicine, King Abdulaziz University, Jeddah, Saudi Arabia info_outline Atlal M. Abusanad, Omar Iskanderani, Marwan R. Al-hajeili, Reem Ujaimi

Authors person Atlal M. Abusanad Faculty of medicine, King Abdulaziz University, Jeddah, Saudi Arabia info_outline Atlal M. Abusanad, Omar Iskanderani, Marwan R. Al-hajeili, Reem Ujaimi Organizations Faculty of medicine, King Abdulaziz University, Jeddah, Saudi Arabia, King Abdulaziz University Faculty of Medicine, Jeddah, Saudi Arabia, King Abdulaziz University, Jeddah, Saudi Arabia Abstract Disclosures Research Funding No funding received Background: Treatment with anti-HER2 therapy can cause CD. The effect of breast XRT, heart dose and V25 of the heart and CT regimen on developing CD is controversial. The impact of these variables in developing CD among patients with HER2-positive breast cancer (BC), receiving CT plus anti-HER2 MoAb was evaluated in routine clinical practice. Methods: Patients with HER2-positive BC between 2015-2019 were included, retrospectively. CD is defined as a drop in (EF%) of at least 10 % points from baseline and/or below 50% at any point of the time during follow-up. The association of CD and various variables was examined with a significance level of < 0.05. Results: Data from 224 female patients were analyzed 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 non-metastatic BC, 52% with comorbidities, 11% had prior IHD medication use in 48%; metformin in 15% and B-blockers in 5%, 9.4% smoker, 70% had a mastectomy, 18% lumpectomy and 12% no surgery, 58% received XRT. The cumulative incidence of CD was 33% during follow-up noting that the first and subsequent drops of EF at any point of time during the follow-up was counted as a new event even for the same patient. The univariate analysis of factors influencing the risk of CD is shown in Table. However, the initial significance of CT regimen and whether the patient received breast XRT or otherwise, did not translate into significance on multivariate analysis with a P -value = 0.198 & 0.326, respectively. Conclusions: XRT mean heart dose and V25 of the heart, anthracycline-based CT did not influence the risk of CD among this cohort. Likewise, the dual anti-HER2 therapy with trastuzumab and pertuzumab and the number of trastuzumab cycles did not influence CD. It is reassuring to demonstrate the safety of these approaches in real-life clinical practice. Univariate analysis of factors influencing the risk of CD. Variable CD N(%) No CD N(%) p-value Anthracycline (AC, FEC, FAC) Non-anthracycline (Docetaxel, Paclitaxel, Carbo+taxane) Other Both (Anthra cycline & taxane) 6 (8) 30 (40) 3 (4) 36 (48) 10 (6.7) 74 (49.7) 21 (14) 44 (29.5) 0.014 Single anti-HER2 (Trastuzumab) Double anti-HER2 (Trastuzumab + Pertuzumab) 63 (84) 12 (16) 129 (86.6) 20 (13) 0.307 No. trastuzumab cycles < 17 >17 64 (85) 11 (14) 132 (88) 17 (11) 0.051 Radiotherapy Yes No Unknown 48 (64) 24 (32) 3 (4) 81 (54) 68 (45.6) 0 (0.0) 0.022 Mean heart dose ≤2.5 >2.5 20 (43) 27 (57) 26 (32) 56 (68) 0.216 V25 of the heart ≤ 5 >5 32 (68) 15 (32) 59 (72) 23 (28) 0.836