Significant Influence of Cardiac Radiation Dose on the Risk of Cardiotoxicity in Patients Receiving Adjuvant Trastuzumab and Radiation Therapy for Breast Cancer

Abstract

Purpose

This study aimed to analyze the incidence of cancer therapy-related cardiovascular toxicity (CTRCVT) and identify the radiation dosimetric and clinical risk factors for these events in patients with human epidermal growth factor receptor 2-positive breast cancer.

Methods and Materials

Data from 1378 patients who were treated with curative surgery and adjuvant trastuzumab for breast cancer were retrospectively analyzed. A total of 959 patients underwent postoperative radiation therapy (RT), whereas 419 patients were managed without RT (no-RT). CTRCVT were categorized according to the time of occurrence in relation to trastuzumab as follows: during trastuzumab cycles (CTRCVT-during T) or after completing trastuzumab (CTRCVT-after T). The cardiac radiation dose was extracted from the RT plan of each individual patient. The incidence of and contributing factors for CTRCVT-during T and -after T were evaluated.

Results

After a median follow-up of 95.8 months (range, 4.3-181.1 months), 69 patients (5.0%) had experienced CTRCVT. CTRCVT-during T was detected in 41 patients (3.0%), and the 8-year rate of CTRCVT-after T was 2.2%. Of the patients developing CTRCVT-during T, 27 (2.0%) discontinued trastuzumab. The cardiac radiation doses were significantly associated with the risk of both CTRCVT-during T (odds ratio, 1.087; P = .001) and -after T (hazard ratio, 1.177; P < .001). The 8-year rates of CTRCVT-after T were not significantly different between the no-RT and RT groups (2.0% vs 2.4%, P = .956). However, the rate was significantly higher in patients with heart V_25Gy ≥3% compared with those with heart V_25Gy <3% (5.7% vs 1.5%, P = .019). Patients who received <17 cycles of trastuzumab had worse oncological outcomes than those who received ≥17 cycles.

Conclusions

Both CTRCVT-during T and -after T were associated with the cardiac radiation dose. Therefore, evaluation of the cardiac radiation dose is necessary to prevent early termination of trastuzumab treatment, which could lead to worse outcomes.