259P - Adjuvant doxorubicin-cyclophosphamide in early-stage breast cancer provides long-term cardiac safety

Background

Anthracyclines have been crucial chemotherapy for breast cancer treatment. However, its use has been limited by cardiotoxicity. We investigated the long-term outcomes and potential biomarkers associated with cardiac toxicities in breast cancer survivors who received anthracycline.

Methods

We prospectively collected data from 212 early-stage breast cancer patients who received adjuvant doxorubicin-cyclophosphamide (AC) at KCMH from 2007 to 2012. Echocardiography was performed pre-AC and within 3 months post-AC in 177 patients. Cardiac MRI (CMR) was conducted in asymptomatic patients (n=49) between July and December 2022 to assess long-term cardiac outcomes. We analyzed plasma microRNA expression using the Nanostring platform at pre-AC and before 2^nd cycle of AC of 18 patients who had decline of LVEF >10% (n= 9) and ≤10% LVEF (n =9).

Results

The mean age of breast cancer diagnosis was 51±9 years with a median follow-up of 11 years [6-12]. The mean cumulative doxorubicin was 223.3±19.8 mg/m². At end-AC evaluation, 43 patients (24.3%) and 15 patients (8.5%) had decreased LVEF by 10-20% and >20% respectively. 32 patients (18%) received subsequent anti-HER2 therapy. 8 patients (3.7%) had arrhythmia (n=6) and cardiomyopathy (n=2) in long-term follow-up. The miR-16-5p, miR-25-3p, miR-873-5p, miR-19b-3p, and miR-30d-5p were the top 5 microRNAs that overexpressed in end-AC LVEF decline >10% with the fold change of 1.77-2.99. There was no difference in long-term CMR findings, including LVEF, LVEDVI, LVESVI, LV mass index, RVEF, T1 mapping, and strain in asymptomatic patients with end-AC LVEF decline >10% vs. ≤10%. Abnormal scars were found in 8 patients who had end-AC LVEF decline >10% (n=7) vs. ≤10% (n=1). All were located at the RV insertion site or mid-wall. Table: 259P

Conclusions

Our study demonstrated acceptable long-term cardiac outcomes in early-stage breast cancer patients who received ≤4 cycles of AC. Potential plasma micro-RNAs were identified and will be further studied in more patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Ethnic Research Initiatives, GSK Oncology International and Matching fund, Faculty of Medicine, Chulalongkorn University.

Disclosure

T. Susiriwatananont: Financial Interests, Personal, Invited Speaker: Roche, Amgen, Novartis. N. Poovorawan: Financial Interests, Personal, Invited Speaker: MSD, Astellas; Financial Interests, Institutional, Invited Speaker: Ipsen. S. Shuangshoti: Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Novartis, Roche; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Biocartis, MiRXES, Takeda. V. Sriuranpong: Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Roche, AstraZeneca, Novartis, MSD, Pfizer, Amgen. All other authors have declared no conflicts of interest.