Cardiac Outcomes Following Adjuvant Radiation Therapy in Triple-Negative Breast Cancer Patients With Prior Autoimmune Myocarditis.

Abstract

Cardiac toxicity during breast cancer treatment can arise from radiation therapy (RT), chemotherapy, and immunotherapy, particularly in triple-negative breast cancer (TNBC). Immune checkpoint inhibitors such as pembrolizumab improve TNBC outcomes but are associated with rare, severe immune-related adverse events, including autoimmune myocarditis. Although RT techniques minimize high-dose cardiac exposure, low-dose exposure may modulate immune activity and potentially reactivate autoreactive T lymphocytes. This study evaluates cardiac events during and after adjuvant RT in patients with TNBC with a history of autoimmune myocarditis. This retrospective bicentric study included 22 patients with T2-T4 or node-positive TNBC treated with pembrolizumab and chemotherapy that developed autoimmune myocarditis during the neoadjuvant phase. Patients subsequently underwent adjuvant RT following surgery. Cardiac toxicity was monitored via echocardiography and clinical assessments, focusing on ventricular dysfunction and symptoms. The primary endpoint was the incidence of cardiac events during RT, early post-RT (≤6 months), and late post-RT (>6 months). Secondary endpoints included survival and radiation-induced toxicities. The cohort's median age was 49 years, with most tumors classified as T1-T2 (86.3%) or as node-negative (59.1%) before the initiation of chemoimmunotherapy. One patient (4.5%) developed asymptomatic ventricular dysfunction (left ventricular ejection fraction 37% at late evaluation), and 5 patients (22.7%) experienced late-onset symptoms, which could potentially be associated with cardiac etiology, including New York Heart Association class II dyspnea and palpitations, despite normal left ventricular ejection fraction and troponin levels. All potential cardiac events/symptoms occurred after RT, even though pembrolizumab had been discontinued. Radiation dermatitis (59.1%) and dysphagia (13.6%) were the most common noncardiac toxicities. At 2 years, recurrence-free survival was 95%, with no reported deaths. This study highlights the potential for late-onset cardiac events or symptoms in patients with TNBC with prior autoimmune myocarditis treated with adjuvant RT. Although most maintained stable cardiac function, a subset developed late-onset ventricular dysfunction or new symptoms despite low mean heart doses and pembrolizumab discontinuation. These findings warrant further investigation of the etiology, including the possibility that immune modulation from RT plays a role.