Evaluating high-sensitivity cardiac troponin I for early detection of treatment-related cardiotoxicity in HER2-positive breast cancer patients

Abstract

Background: Trastuzumab-related cardiotoxicity is a common adverse effect of HER2-positive breast cancer treatment, especially when combined with anthracyclines. However, to date, no definitive prognostic markers have been found to predict trastuzumab-related cardiotoxicity.

Methods: Patients diagnosed with HER2-positive breast cancer, scheduled to receive anthracyclines followed by 12 months of trastuzumab or with pertuzumab, were prospectively followed up for 27 months. Measurements of left ventricular ejection fraction LVEF, high-sesitivity troponin I hs-Tn I, and a full cardiac examination were performed at baseline, after anthracycline treatment, and after four cycles of anti-HER2 agents. Subsequently, LVEF measurement and full cardiac examination were conducted every 3 months until the end of the follow-up. Cardiotoxicity was defined as an absolute decrease in LVEF of ≥15%, or a drop in LVEF of ≥10% from the baseline to <50%.

Results: Among 78 patients, cardiotoxicity occurred in 13 (16.7%). A higher risk of cardiotoxicity was linked to hs-Tn I measured after four cycles of anti-HER2 agents (P < 0.001), with a significant cutoff of >84 ng/L. No short-term effects of the anthracycline agents (doxorubicin or epirubicin), were found. However, there was a slightly higher tendency to develop cardiotoxicity (P = 0.046) in patients treated with trastuzumab plus pertuzumab.

Conclusion: Hs-Tn I measured after four cycles of trastuzumab in HER2-positive breast cancer patients could be an important predictor of cardiotoxicity induced by chemotherapy followed by anti-HER2 agents, particularly in the first year post-treatment, with a different cutoff value than that used in other cardiac conditions.

Keywords: HER2+ breast cancer; anthracycline; cardiotoxicity; trastuzumab; troponin I.

Figure 1.

Study protocol. Phase 0: baseline; refers to the time when breast cancer diagnosis was made. Phase 1: 4 AC 0 H/P: refers to the time when the patient ended the four cycles of anthracyclines before starting the anti-HER2 regimen (AC: anthracyclines; H: trastuzumab; P: pertuzumab). Phase 2: after four cycles of anti-HER2 agents. Phase 3: 3 months after the end of the treatment: after 18 months of starting the full regimen. Phase 4: End of follow-up: after 27 months; the time point after ending the full treatment course.

Figure 2.

Study population. AF, atiral fibrillation, HTN, hypertension, pHTN, pulmonary hypertension.

Figure 3.

EF changing during all study points.

Figure 4.

LVEF mean change during all study phases among patient groups (total, no cardiotoxicity, cardiotoxicity). LVEF: left ventricular ejection fraction.

Figure 5.

ROC curves of hs-Tn I for developing cardiotoxicity. (A) hs-Tn I values after four cycles of trastuzumab for developing cardiotoxicity; (B) hs-Tn I values after four cycles of anthracyclines for developing cardiotoxicity.

Figure 6.

A risk stratification suggested protocol before starting the cancer treatment.