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 Table 3 – Aspirin and selective estrogen receptor modulators (SERMs) Author, year Type of study Patients (n) SERMs and/or aspirin Main Conclusions Holmes et al., 40 2008 Clinical trial 30 Tamoxifen or aromatase inhibitor + ASA ASA attenuated the increase in VEGF associated with tamoxifen Holmes et al., 44 2010 Prospective Cohort 4,164 ASA Reduction in the recurrence and death from breast cancer Holmes et al., 41 2013 Clinical trial 12 Tamoxifen + ASA Reduction in VEGF and increase in TSP-1 Holmes et al., 45 2014 Case-control 27,426 ASA There is no benefit during end-stage illness Yang et al., 46 2017 Retrospective Cohort 148,739 ASA Reduction in breast cancer risk in diabetics Fraser et al., 47 2014 Cohort 4,627 ASA Reduction in death risk from all causes Jhonson et al., 48 2002 Prospective Cohort 27,616 ASA Reduction in breast cancer risk Harris et al., 53 1999 Prospective Cohort 32,505 ASA/ibuprofen Reduction in breast cancer risk Duvernoy et al., 43 2010 (RUTH Trial) Clinical trial 10,101 Raloxifene + ASA Did not change the risk of VTE ASA: acetylsalicylic acid; VEGF: vascular endothelial growth factor; TSP-1: thrombospondin 1; VTE: venous thromboembolism. Cheng et al. 42 carried out a study that showed that aspirin not only inhibits the growth of the MCF-7 RE-positive breast cancer cell line, but also has a potential function to overcome resistance to tamoxifen in MCF-7/TAM cell lines. The concomitant action of aspirin makes cells more sensitive to tamoxifen, indicating that aspirin can regulate proteins to overcome tamoxifen resistance. The RUTH 21 study evaluated the effects of antiplatelet therapy concomitant with the use of raloxifene regarding the risk of VTE. The increased risk of VTE with raloxifene when compared to placebo was not different between the women who used antiplatelet agents and those who did not use it. 43 The key findings of the abovementioned studies are summarized in Table 3. Aspirin and Cancer Prevention A prospective observational study of 4,164 women with breast cancer showed that, among women who were alive at least 1 year after the breast cancer diagnosis, the use of aspirin was associated with a reduction in the risk of recurrence and death from breast cancer. 44 Contrarily, another study with 27,426 women with breast cancer showed that there was no association between aspirin use and death from breast cancer. 45 A retrospective cohort study was carried out in Taiwan with 148,739 diabetic women, of which 27,378 used aspirin at a dose ranging from 75 mg to 165 mg/day, which were compared to women who did not use aspirin. Overall, aspirin use reduced the risk of breast cancer by 18% (Hazard Ratio – HR= 0.82, 95%CI: 0.71-0.94). Specifically, a cumulative dose of aspirin > 88,900mg was observed to reduce the risk of breast cancer by 47% . 46 A cohort in Scotland identified 4,627 women with breast cancer throughout 11 years. The use of aspirin after the diagnosis was identified in 1,035 women (22.4%). Most of them used a 75 mg dose/day. It was concluded that low-dose aspirin was associated with reduced risk of death from all causes and breast cancer. 47 Another cohort, with 27,616 postmenopausal women, identified 938 cases of breast cancer in 6 years of follow-up, meaning a RR of 0.71 (95% CI: 0.58-0.87) for those who took aspirin at least six times a week, when compared with those who did not use the medication. 48 Evidence from case-control and cohort studies suggest an approximately 10% reduction in the risk of breast cancer for aspirin use. 49,50 Similar results were found with other NSAIDs and Cycloxygenase-2 inhibitors (COX-2). 51 Rothwell et al. 52 analyzed seven randomized trials for the regular use of aspirin with a minimum duration of 4 years to determine the effect of aspirin on the risk of death from cancer. Daily aspirin reduced death rates from several types of cancer during and after the studies. The benefit increasedwith treatment duration andwas consistent in all the different studied populations. Harris et al. 53 found 393 cases of breast cancer in 32,505 patients after 5 years of follow-up. This study reported a 50% reduction in the incidence of breast cancer using ibuprofen (p < 0.01) and 40% with regular aspirin use (p < 0.05), suggesting that other NSAIDs may also be effective in breast cancer prophylaxis. Aspirin emerged as the most likely NSAID for use in chemoprevention due to its benefits also in preventing cardiovascular events. Other NSAIDs have also been studied as adjuvants in the chemoprevention of several types of cancer, especially colorectal, breast and stomach neoplasms, although these drugs do not offer cardioprotection. 54 Mortality reduction is more evident in colon cancer, probably in prostate and possibly also in breast neoplasms. 55,56 Discussion The clinical trials mentioned in this review report an increase in VTE with the use of SERMs and, regarding cerebrovascular and coronary events, the results were discordant. The currently used treatment, consisting of chemotherapy and hormone therapy, has reduced breast cancer mortality, but morbidity 209