Key result
Dual anti-HER2 therapy shows no added early cardiotoxicity over trastuzumab alone during radiotherapy.
Why the study?
It was unclear whether dual anti-HER2 therapy with trastuzumab and pertuzumab increases early cardiac toxicity compared to trastuzumab alone in breast cancer patients receiving postoperative radiation therapy.
Does dual anti-HER2 therapy increase early cardiac toxicity compared to trastuzumab alone in operable breast cancer patients receiving postoperative radiation therapy?
Cohort (n=681)
Yes
Does dual anti-HER2 therapy increase early cardiac toxicity compared to trastuzumab alone in operable breast cancer patients receiving postoperative radiation therapy?
Dual anti-HER2 therapy does not significantly increase early cardiac toxicity compared to trastuzumab alone in breast cancer patients receiving postoperative radiation therapy, with cardiac radiation exposure remaining the primary risk factor.
May support dual anti-HER2 safety in this cohort; leaves open prospective validation of radiation-related ECG risks.
PURPOSE: This study aims to assess whether dual anti-HER2 therapy with trastuzumab and pertuzumab increases early cardiac toxicity compared to trastuzumab alone in breast cancer (BC) patients receiving postoperative radiation therapy (RT). METHODS: Consecutive operable BC patients receiving postoperative RT and trastuzumab with or without pertuzumab between January 2017 and September 2020 at seven tertiary hospitals in China were retrospectively reviewed. Cardiac examinations included echocardiography, electrocardiogram (ECG), NT-proBNP, and cTnI at baseline before RT and during the follow-up. The cardiac event is any new-onset symptomatic heart disease or abnormality in the cardiac examination after RT. RESULTS: In total, 681 patients were enrolled in the analysis, of whom 567 were treated with trastuzumab-alone and 124 patients received dual anti-HER2 therapy. The median follow-up was 11 months. Multivariate analysis showed that left-sided breast cancer (HR 2.38; 95%CI 1.65-3.44, p < 0.001) and IMN RT (HR 1.47; 95 % CI 1.01-2.15, P-value = 0.047) are independent risk factors for ECG abnormalities. Age >50 years is an independent risk factor for developing LVDD (HR 5.16; 95%CI 1.17-22.73, P-value = 0.030). Dosimetric analysis showed that patients who developed subclinical cardiac events had increased mean heart dose (412.0 ± 249.6 vs. 347.2 ± 242.6 cGy, P-value = 0.010). Among right-sided patients or patients receiving anthracycline-based chemotherapy, the dual-targeted cohort had a higher risk of developing ECG abnormalities compared to the trastuzumab-only cohort. CONCLUSION: Compared with trastuzumab-only, dual anti-HER2 therapy does not increase early cardiac toxicity in combination with postoperative RT in BC patients. Cardiac radiation exposure remains the primary risk factor for early toxicity.
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Zhou et al. (2025) conducted a cohort in operable breast cancer (n=681). Dual anti-HER2 therapy (trastuzumab and pertuzumab) vs. Trastuzumab alone was evaluated on Early cardiac toxicity (any new-onset symptomatic heart disease or abnormality in the cardiac examination after RT). Dual anti-HER2 therapy did not increase early cardiac toxicity vs trastuzumab alone, whereas left-sided breast cancer independently increased ECG abnormalities (HR 2.38; 95% CI 1.65-3.44).
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