Messaggi chiave
- La disfunzione cardiaca rappresenta la prima causa di morte nei pazienti con carcinoma mammario (BC) sopravvissuti a 10 anni dalla diagnosi. Tuttavia, vi sono poche informazioni disponibili in merito all’incidenza del problema e ai relativi fattori di rischio nei pazienti BC esposti a terapie cardiotossiche in un contesto real-world e seguiti nel lungo termine.
- Gli autori del presente studio hanno valutato 2808 ecocardiogrammi (ECO) di 829 sopravvissuti a BC sottoposti a monitoraggio ECO ogni 2 anni dopo il completamento della terapia cardiotossica e seguiti per un follow-up mediano di 8,6 anni. È stato osservato un aumento dell’incidenza cumulativa di disfunzione cardiaca dall’1,8% a 2 anni al 15,3% a 15 anni. L’analisi multivariata ha consentito di identificare i seguenti fattori di rischio: etnia nera non ispanica; pregressa terapia cardiotossica (antracicline ± radioterapia [RT] [soprattutto disfunzione tardiva] oppure antracicline e trastuzumab/pertuzumab ± RT [soprattutto disfunzione precoce] rispetto a sola RT della mammella sinistra); trattamento con modulatori selettivi del recettore estrogenico; e ipertensione precedente la diagnosi.
- Le analisi longitudinali aggiustate hanno evidenziato un declino annuale nella frazione di eiezione del ventricolo sinistro dello 0,29% (p = 0,009) nell’arco dei 20 anni successivi alla diagnosi. Nel complesso, i risultati dello studio supportano l’adozione di rigorosi protocolli di sorveglianza ecocardiografica dopo l’esposizione a terapie potenzialmente cardiotossiche e suggeriscono altresì la necessità di un’adeguata gestione dei fattori di rischio modificabili.
Abstract
Purpose
- Cardiac dysfunction is the leading cause of mortality among 10-year breast cancer survivors.
- Limited information regarding long-term risks of cardiac dysfunction after cardiotoxic therapy (anthracyclines, trastuzumab/pertuzumab, radiation) has precluded development of surveillance guidelines for the survivors.
Methods
- Patients with breast cancer who completed cardiotoxic therapy underwent echocardiographic screening every 2 years.
- New-onset cardiac dysfunction was defined as left ventricular ejection fraction (LVEF) <50% after cardiotoxic therapy initiation and included early- and late-onset cardiac dysfunction.
Results
- We evaluated 2,808 echocardiograms in 829 breast cancer survivors; the median age at breast cancer diagnosis was 54.2 years (range, 20.3-86.3); the median follow-up was 8.6 years (1.8-39.8); 39.7% received anthracyclines, 16% received trastuzumab/pertuzumab, 6.2% received both anthracyclines and trastuzumab/pertuzumab, and 38.1% received radiation alone.
- The cumulative incidence of cardiac dysfunction increased from 1.8% at 2 years to 15.3% at 15 years from cardiotoxic therapy initiation.
- Multivariable Cox regression analysis identified the following risk factors: non-Hispanic Black race (HR, 2.15 [95% CI], 1.37 to 3.38), cardiotoxic therapies (anthracyclines: HR, 2.35 [95% CI, 1.25 to 4.4]; anthracyclines and trastuzumab/pertuzumab: HR, 3.92 [95% CI, 1.74 to 8.85]; reference: left breast radiation alone), selective estrogen receptor modulators (HR, 2.0 [95% CI, 1.2 to 3.33]), and precancer hypertension (HR, 3.16 [95% CI, 1.63 to 6.1]).
- Late-onset cardiac dysfunction was most prevalent among anthracycline- and radiation-exposed patients; early-onset cardiac dysfunction was most prevalent among patients exposed to anthracyclines and trastuzumab/pertuzumab; equal prevalence of both early- and late-onset cardiac dysfunction was observed in trastuzumab-/pertuzumab-exposed patients.
- Adjusted longitudinal analyses revealed an annual decline in LVEF by 0.29% (p = 0.009) over 20 years from breast cancer diagnosis.
Conclusions
- These findings provide evidence to support echocardiographic surveillance for several years after cardiotoxic therapy and also suggest a need to examine the efficacy of management of cardiovascular risk factors to mitigate risk.