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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 V25Gy ≥3% compared with those with heart V25Gy <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.

Affiliations

Tae Hoon Lee 1, Nalee Kim 1, Eun Kyoung Kim 2, Jin Seok Ahn 3, Yeon Hee Park 3, Seok Won Kim 4, Jeong Eon Lee 4, Jonghan Yu 4, Byung Joo Chae 4, Se Kyung Lee 4, Won Kyung Cho 1, Won Park 1, Tae Gyu Kim 5, Jee Suk Chang 6, Haeyoung Kim 7
1Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
2Division of Cardiology, Heart Vascular and Stroke Institute, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
3Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
4Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine.
5Department of Radiation Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
6Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
7Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: hykim0131@skku.edu.