Expert Opinion on the use of Anthracyclines in Patients With Advanced Breast Cancer at Cardiac Risk

P.J. Barrett-Lee; J.M. Dixon; C. Farrell; A. Jones; R. Leonard; N. Murray; C. Palmieri; C.J. Plummer; A. Stanley; M.W. Verrill

Disclosures

Ann Oncol. 2009;20(5):816-827. 

In This Article

Abstract and Introduction

Abstract

Anthracyclines are considered to be among the most active agents for the treatment of breast cancer. However, their use is limited by cumulative, dose-related cardiotoxicity. Such cardiotoxicity results in a permanent loss of cardiac myocytes and a progressive reduction in cardiac function following each subsequent dose of anthracycline. Initially, damage to the heart is subclinical; however, increasingly impaired cardiac function can result in cardiovascular symptoms, with serious cardiac injury resulting in chronic heart failure. Since the early detection and treatment of cardiotoxicity can reduce its clinical effects, it is important that oncologists are aware of these adverse effects and manage them appropriately. This review examines the risk factors for anthracycline-associated cardiotoxicity and offers recommendations on strategies to reduce the cardiotoxicity of anthracyclines in the management of patients with advanced breast cancer.

Introduction

Since their introduction in the 1960s, the anthracyclines, doxorubicin and epirubicin, have been considered to be among the most active agents for the treatment of breast cancer and are components of many adjuvant and palliative regimens.[1] Their clinical utility is, however, limited by cumulative, dose-related progressive myocardial damage that may lead to chronic heart failure (CHF), reduced quality of life, or death.[2,3] Several other established and future chemotherapies for breast cancer are also known to have potentially important adverse effects on the cardiovascular system.[4] These include taxanes, alkylating agents (e.g. cisplatin), antimetabolites (e.g. capecitabine), and mitoxantrone as well as some of the newer targeted agents, such as trastuzumab, bevacizumab, and the tyrosine kinase inhibitor, sunitinib.[4,5,6,7] Radiation therapy to the chest has also been shown to have cardiotoxic effects.[4] Recently, there have been concerns that the use of aromatase inhibitors in breast cancer increases cardiovascular risk, especially as tamoxifen may protect against cardiovascular disease.[8,9] As an increasing number of women survive breast cancer, the impact of cancer treatment on cardiovascular health is becoming ever more important. Since the early detection and treatment of cardiotoxicity can reduce its clinical effects, it is particularly important that oncologists are aware of these side-effects and manage them appropriately.[10]

The sequential and concomitant use of adjuvant therapies, combined with other risk factors, such as age, obesity, and physical inactivity, may increase cardiovascular vulnerability and, ultimately, the risk of premature cardiovascular-associated mortality in patients with breast cancer--a phenomenon labelled the 'multiple-hit' hypothesis.[4] The consequences of the multiple-hit have important implications for the use of chemotherapy in women with advanced breast cancer.[4,11] Although these patients may already be at an increased cardiac risk because of their adjuvant treatment or biological risk factors, they may still benefit from anthracycline therapy to treat their cancer. Since 50% of women who develop breast cancer are older than 61 years,[12] it is important that clinicians are aware of preexisting co-morbidities and the short- and long-term cardiovascular effects that are associated with cancer treatments.[13] Several strategies have been developed to reduce anthracycline-induced cardiotoxicity; however, no consensus currently exists on optimal monitoring for associated adverse cardiac effects in patients with advanced breast cancer.[14]

This paper reviews the key evidence and risk factors for anthracycline-associated cardiotoxicity and offers recommendations on strategies to reduce the cardiotoxicity of anthracyclines in the management of patients with advanced breast cancer. The recommendations are not intended to be prescriptive, but their aim is to help clinicians identify patients with advanced breast cancer at increased risk of cardiotoxicity, so that appropriate decisions regarding the use and monitoring of anthracycline therapy can be made.

Search Strategy and Selection Criteria

Data for this review were identified by searches of the Medline database using the search terms 'breast', 'carcinoma', 'cancer', 'cardiac*', 'heart', 'cardio*', 'cardiov*', 'cardiotox*', 'toxic*', 'chemotherapy*', 'anthracycline*', 'lifestyle', 'risk', 'behaviour*', 'comorbid*', and 'co-morbid*'. The search results were supplemented by manual searching of current journals, reference lists in key articles and other appropriate documents, and expert input.

All recommendations are based on the best available evidence supplemented by the authors' experiences in managing advanced breast cancer.

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