Abstract P2-11-06: HER2 positive breast cancer and subclinical cardiotoxicity by echocardiogram 2D Strain, Do chemotherapy sequence matter?
Authors: Pérez-Montessoro V , Poblano-Aguilar I , Galindo-Uribe J , Vásquez-Ortiz Z , Armengol-Alonso A 
Published: March 2017

Background: Even when there are free schemes of anthracyclines, the biological subtype HER2+ can be exposed to cardiotoxic drugs anthracyclines (A) and/or trastuzumab(H). It has been demonstrated that the LVEF is not sensitive to detect early cardiac changes and could be within normal ranges but with irreversible cardiac dysfunction. 2D speckle tracking and cardiac biomarkers (TnI and NT-proBNP) have shown more sensitivity to define early myocardial damage. Adjuvant trial FinHER suggests lower cardiotoxicity (0.5%) when taxanes (T)+H are given before A. Our objectives were: 1)To show higher sensitivity of the longitudinal strain in the echo to detect cardiotoxicity compared to the LVEF 2)To describe if there are any differences in the cardiotoxicity in relation with the chemotherapy sequence used.

Patients and methods: A retrospective cohort of patients diagnosed with breast cancer from February 2008 to January 2016 was obtained, in which 46 patients with HER2 positive breast cancer were included, most in the context of neoadjuvant or adjuvant chemotherapy treated with sequential chemotherapy (A→T+H vs T+H→A), with a cumulative dose of 240 mg/m2 of doxorubicin. A basal echo was done, as well at 3, 6, 9, 12 months after the beginning of the chemotherapy to determine LVEF and early cardiac damage parameters, such as longitudinal strain. Cardiotoxicity was determined with a symptomatic HF with a decline of LVEF &gt;5% or LVEF ≤55% or asymptomatic HF with a decline ≥10% or in LVEF or LVEF ≤55%. A fall ≥15% was considered a significant decline of the longitudinal strain

Results: 1 patient (2.1%)presented symptomatic HF (NYHA III). Asymptomatic cardiotoxicity was present in 9 patients (19.6%), 9 (19.6%), 11 (23.9%), and 13 (28.3%) at the 3, 6, 9, and 12 months respectively. The mean LVEF were (66±6.6), (63±9.0), (65±7.0), (65±6.4), and (63±6.9) at the basal, 3, 6, 9, and 12 months measurements respectively, with a non-significant “p” value. Significant decline in the longitudinal strain was observed in 10 patients (21.7%, p=0.012), in 13 patients (28.3%, p=0.034), in 15 patients (32.6%, p=0.95), and in 18 patients (39.1%, p=0.07), at the 3, 6, 9, and 12 months measurements respectively. When comparing the cardiotoxicity group vs the non cardiotoxicity groups no significant differences were observed with other risk factors as: HTN, dyslipidemia, carbohydrate intolerance, DM, radiotherapy, weight, cumulative doses of A, systolic-diastolic BP, glc levels, HDL, TG, and BMI. In the logistic regression analysis the longitudinal strain decline (≥15%) basal vs 3 months measurement had a OR 7.63 CI 95%(1.04-55.86) and the A→T + H sequence OR 7.7 CI 95%(1.076-55.43), were kept as independent variables for cardiotoxicity.

Conclusions: As reported in literature the decline in the longitudinal strain was more sensitive than the LVEF to predict cardiotoxicity, thus this would allow to identify the highest risk individuals and to start a cardioprotective intervention. Due to the retrospective character of our study, we believe that in the neoadjuvant or adjuvant chemotherapy setting of sequential chemotherapy there is the need of prospective studies that evaluate the subclinical cardiotoxicity with more sensitive parameters to confirm our data.

Citation Format: Pérez-Montessoro V, Poblano-Aguilar I, Galindo-Uribe J, Vásquez-Ortiz Z, Armengol-Alonso A. HER2 positive breast cancer and subclinical cardiotoxicity by echocardiogram 2D Strain, Do chemotherapy sequence matter? [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-11-06.