ABC | Volume 111, Nº2, August 2018

Review Article Leite et al Aspirin and hormonal therapy in breast cancer Arq Bras Cardiol. 2018; 111(2):205-212 Figure 1 – Flowchart of the evaluated studies. 221 reports identified in the databases 15 articles retrieved from other sources 77 abstracts after removing duplicates 57 selected abstracts 32 full-text articles assessed for eligibility 27 studies included in the qualitative synthesis 25 excluded (PICO criteria) : Exclusion: (2) animal model; (2) case reports; (1) Comment Identification Selection Eligibility Inclusion A total of 221 abstracts met the search criteria and other 15 were manually retrieved. A total of 159 duplicated articles were eliminated and 77 abstracts were evaluated. Of these, 57 were selected for the review. We excluded 25 because they did not meet the previously established criteria, resulting in 32 full-text articles, which were evaluated in relation to their scientific quality. Five articles were excluded according to the inclusion/exclusion criteria. A total of 27 articles were analyzed, according to figure 1. Selective estrogen receptor modulators and reduction of morbidity and mortality in breast cancer Most breast cancers have positive ER and three main drugs are being used for their treatment and/or prevention, namely: tamoxifen, raloxifene and toremifene. All of these agents are competitive inhibitors of estrogen binding to its receptors, and have mixed agonist and antagonist activity, depending on the target tissue. 5 Tamoxifen is the most well-studied SERM and often the drug of choice for breast cancer treatment. Its mechanism of action involves tumor cell growth inhibition through competitive ER inhibition. 6 The benefits of tamoxifen have been consolidated through the US Financial Service Task Force (USPSTF) meta-analysis. 7 In comparison with placebo, the use of tamoxifen resulted in: reduced risk of invasive breast cancer (Relative Risk – RR = 0.70; 95% Confidence Interval – 95%CI: 0.59-0.82); reduction in the incidence of non-vertebral fractures (RR=0.66, 95%CI: 0.45‑0.98); and no difference in mortality from breast cancer or from all causes. On the other hand, a pro-coagulant effect is described when tamoxifen is added to chemotherapy – especially an increase in thromboembolic events. 8,9 Raloxifene differs from tamoxifen because it does not stimulate endometrial tissue, although it exerts the same beneficial effects of tamoxifen on breast tissue. In preclinical studies, raloxifene has been shown to prevent the onset of new breast cancers, as well as prevent the growth of preexisting cancers. 10 In the STAR (Study of Tamoxifen and Raloxifene) study, 11 19,747 women were randomized to receive 20 mg of tamoxifen or 60 mg/day of raloxifene for 5 years. The results showed that raloxifene had the same efficacy as tamoxifen in the prevention of breast cancer in situ , both with a 50% risk reduction (RR of 1.02, 95%CI: 0.82-1.28). However, raloxifene did not show protection against invasive types of breast cancer, whereas tamoxifen reduced its incidence by around 50%. It was observed that the group treated with raloxifene had an almost 30% reduction in thromboembolic events such as Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) (RR = 0.70, 95%CI: 0.54-0.91). Both groups had the same incidence of cerebrovascular accident, myocardial infarction and fractures. The MORE (Multiple Outcomes of Raloxifene Evaluation) 12 study randomized 7,705 postmenopausal patients who had osteoporosis and had no history of breast or endometrial cancer for the use of placebo or 60 mg/day or 120 mg/day of raloxifene. After 4 years of follow-up, a 72% reduction of breast cancer risk was observed. 13 In the CORE (Continuing Outcomes relevant to Evista) study, 14 the patients were randomized to either raloxifene 60 mg/day or placebo. A 59% reduction (RR = 0.41, 95%CI: 0.24-0.71) was observed in the incidence of breast cancer and a decrease of 66% (RR = 0.34, 95%CI: 0.18-0.66 ) of ER-positive invasive breast cancer, when compared with the placebo group. When analyzing both studies together, the incidence of invasive breast cancer was reduced by 66% (RR = 0.34, 95% CI: 0.22‑0.50) and, for ER‑positive cases, 76% (RR = 0.24, 95%CI: 0.15‑0.40), relative to the placebo group. No protection was observed against non-invasive cancers. 206