ABC | Volume 111, Nº2, August 2018

Review Article Antiplatelet Therapy in Breast Cancer Patients Using Hormonal Therapy: Myths, Evidence and Potentialities – Systematic Review Andréa de Melo Leite, 1,2 Ariane Vieira Scarlatelli Macedo, 3 Antonio José Lagoeiro Jorge, 1 Wolney de Andrade Martins 1 Programa de Pós-graduação em Ciências Cardiovasculares da Universidade Federal Fluminense (UFF), 1 Niterói, RJ - Brazil Rede D'Or São Luiz, 2 Rio de Janeiro, RJ - Brazil Grupo Oncoclínicas do Brasil, 3 Belo Horizonte, MG - Brazil Keywords Breast Neoplasms/drug therapy; Indicators of Morbidity and Mortality; Aspirin; Tamoxifen; Raloxilene Hydrochloride; Cardiovascular Diseases/prevention & control; Selective Estrogen Receptor Modulators. Mailing Address: Andréa de Melo Leite • Rua Marques do Paraná, 303. Postal Code 24030-215, Niterói, RJ - Brazil E-mail: andreamelo@cardiol.br , andreamelocardiologia@gmail.com Manuscript received October 25, 2017, revised manuscript June 06, 2018, accepted June 12, 2018 DOI: 10.5935/abc.20180138 Abstract Breast cancer is the most frequently diagnosed tumor in women worldwide, with a significant impact on morbidity and mortality. Chemotherapy and hormone therapy have significantly reduced mortality; however, the adverse effects are significant. Aspirin has been incorporated into clinical practice for over 100 years at a low cost, making it particularly attractive as a potential agent in breast cancer prevention and as an adjunct treatment to endocrine therapy in the prophylaxis of cardiovascular complications. The objective of this study was to evaluate the role of aspirin in reducing the incidence of breast cancer and to evaluate the impact of its use on morbidity and mortality and reduction of cardiovascular events as adjuvant therapy during breast cancer treatment with selective estrogen receptor modulators. A systematic review was performed using the PRISMA methodology and PICO criteria, based on the MEDLINE, EMBASE and LILACS databases. The original articles of clinical trials, cohort, case‑control studies and meta-analyses published from January 1998 to June 2017, were considered. Most studies showed an association between the use of selective estrogen receptor modulators and the increase in thromboembolic events. The studies suggest a protective effect of aspirin for cardiovascular events during its concomitant use with selective estrogen receptor modulators and in the prevention of breast cancer. This systematic review suggests that aspirin therapy combines the benefit of protection against cardiovascular events with the potential reduction in breast cancer risk, and that the evaluation of the benefits of the interaction of endocrine therapy with aspirin should be further investigated. Introduction Breast cancer is the most frequently diagnosed tumor in women worldwide, with a significant impact on morbidity and mortality. According to the World Health Organization, it is estimated that more than 1.5 million new cases of breast cancer are annually diagnosed worldwide. Despite advances in treatment, breast cancer mortality is still high, with 570,000 deaths in 2015. The disease, recurrent or metastatic, remains incurable in most cases. 1 Chemotherapy and hormone therapy have significantly reduced mortality, but their adverse effects are considerable. Endocrine therapy has revolutionized the treatment of breast cancer patients with positive Estrogen Receptor (ER), although there are cases that develop resistance to this therapy. An appropriate strategy would be the combination of Selective Estrogen ReceptorModulators (SERMs) or another hormonal class with other therapeutic agents, aiming at attaining a synergistic antitumor effect. The use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, has been associated with reduced risk of breast cancer. 2,3 This therapy could also antagonize thrombogenic effects in women treated with tamoxifen. The increasing number of breast cancer survivors is confronted with the shortage of information among clinicians on the subject. The aim of the present study is to evaluate the role of aspirin in reducing the incidence of breast cancer and to evaluate the impact of its use in reducing cardiovascular events as an adjuvant therapy during the treatment of breast cancer with SERMs. Methods This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) methodology. 4 The study included original articles of clinical trials, cohort, case-control studies and meta-analyses published from January 1998 to June 2017, with full-texts in English, Spanish and Portuguese, obtained from the MEDLINE, EMBASE and LILACS databases. The research was performed using the following descriptors: (selective estrogen receptor modulators OR tamoxifenOR raloxifene hydrochloride OR toremifene) AND (platelet aggregation inhibitors OR aspirin) AND (cardiovascular disease) AND (breast CA). This study was based on the PICO (acronym for Population, Intervention, Control and Outcome) criteria. The objective was to evaluate whether aspirin use implies in the reduction of events, especially cardiovascular events, in women with breast cancer using SERMs. The studies were selected according to the following criteria: use of SERMs in women with breast cancer; regular aspirin use; and evaluation of mortality, metastases, and adverse effects using SERMs and/or aspirin. Case reports, articles with other types of endocrine therapy, and animal experimental models were excluded. 205