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

Int J Radiat Oncol Biol Phys. 2025 Aug 1;122(5):1113-1124. doi: 10.1016/j.ijrobp.2024.11.009. Epub 2024 Nov 15.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological* / adverse effects
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Breast Neoplasms* / chemistry
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / radiotherapy
  • Breast Neoplasms* / therapy
  • Cardiotoxicity* / epidemiology
  • Cardiotoxicity* / etiology
  • Chemotherapy, Adjuvant / adverse effects
  • Female
  • Heart* / drug effects
  • Heart* / radiation effects
  • Humans
  • Incidence
  • Middle Aged
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant / adverse effects
  • Retrospective Studies
  • Risk Factors
  • Trastuzumab* / adverse effects
  • Trastuzumab* / therapeutic use

Substances

  • Trastuzumab
  • Antineoplastic Agents, Immunological