Evaluation and management of chemotherapy-induced cardiotoxicity in breast cancer: a Delphi study

Abstract

Purpose: While much progress has been made in the treatment of breast cancer, cardiac complications resulting from therapy remain a significant concern. Both anthracyclines and novel targeted agents can inflict cardiac damage. The present study aimed to evaluate the difference between what it is currently done and what standards of care should be used to minimizing and managing cardiac toxicity in breast cancer survivors.

Methods: A two-round multicenter Delphi study was carried out. The panel consisted of 100 oncologists who were asked to define the elected therapies for breast cancer patients, the clinical definition and patterns of cancer drug-derived cardiac toxicity, and those protocols focused on early detection and monitoring of cardiovascular outcomes.

Results: Experts agreed a more recent definition of cardiotoxicity. Around 38 % of patients with early-stage disease, and 51.3 % cases with advanced metastatic breast cancer had preexisting risk factors for cardiotoxicity. Among risk factors, cumulative dose of anthracycline ≥450 mg/m² and its combination with other anticancer drugs, and a preexisting cardiovascular disease were considered the best predictors of cardiotoxicity. Echocardiography and radionuclide ventriculography have been the proposed methods for monitoring changes in cardiac structure and function. Breast cancer is generally treated with anthracyclines (80 %), so that the panel strongly stated about the need to plan a strategy to managing cardiotoxicity. A decline of left ventricular ejection fraction (LVEF) >10 %, to an LVEF value <53 % was suggested as a criterion for changing the dose schedule of anthracyclines, or suspending the treatment of chemotherapy plus trastuzumab until the normalization of the left ventricular function. The use of liposomal anthracyclines was strongly suggested as a treatment option for breast cancer patients.

Conclusions: The present report is the first to produce a set of statements on the prevention, evaluation and monitoring of chemotherapy-induced cardiac toxicity in breast cancer patients.

Keywords: Anthracycline; Breast cancer; Cardiotoxicity; Delphi study; Trastuzumab.

Fig. 1

Current profile of breast cancer patients attended by the Spanish Delphi panel. Results are presented as a mean percentage (%; 95 % CI) of early-stage breast cancer patients (ESBC; 95 % CI 55–66); or metastatic breast cancer patients (MBC; 95 % CI 33.4–47.2) treated with chemotherapy, and those who refers at least one risk factor (RF) to develop cardiotoxicity (ESBC + RF, 95 % CI 30.3–40.2; MBC + RF, 95 % CI 47.2–58.9)

Fig. 2

Frequencies of cancer therapy drugs used in early-stage (a) and metastatic breast cancer patients (b). CT chemotherapy

Fig. 3

Graphic representation of the Likert scale mean values of the selected statements to rate the need for intervention of anthracycline-related risk factors (a) and patient-related risk factors (b) for cardiac toxicity in early-stage and metastatic breast cancer. Likert scale ranged from 1—no need at all to 7—absolutely needed. ESBC early-stage breast cancer, MBC metastatic breast cancer

Fig. 4

Preferential order of recommended techniques for serial monitoring of cardiac function during chemotherapy (a) and its practical use either by scientific evidence or availability, or not used (b). Results are presented as a mean percentage (95 % CI; %) of respondents (n = 100). BMKs biomarkers, RV radionuclide ventriculography, Eco echocardiography

Fig. 5

Strategies to minimize cardiotoxicity related to the cancer therapy (a) or to the treatment of cardiac dysfunction (b). Results are presented as a mean percentage (95 % CI; %) of respondents (n = 100). Cardiotoxicity was defined as a reduction of LVEF >10 % to below the normal limit LVEF <53 %

Fig. 6

Evaluation for the need of liposomal anthracyclines in patients with advanced breast cancer, and with or without risk factors associated with cardiotoxicity (based on a 7-point Likert scale, where 1 means never recommended and 7 indicates always recommended)