Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review

Abstract

ObjectiveTo investigate the effect of endocrine therapies on a wide range of specific clinical cardiovascular disease outcomes in women with a history of non-metastatic breast cancer.DesignSystematic review and meta-analysis of randomised controlled trials and observational studies.Data sourcesMedline and Embase up until June 2018.Eligibility criteria for selecting studiesStudies were included if they investigated the risk of a specific cardiovascular disease outcome associated with use of either tamoxifen or an aromatase inhibitor, or compared the two treatments, in women with a history of non-metastatic breast cancer.Appraisal and data extractionRelevant studies were originally identified and results extracted by one researcher, with a full replication of the study identification process by a combination of two other researchers. The Cochrane Collaboration’s tool for assessing risk of bias was used to assess risk of bias in randomised controlled trials, and this tool was adapted to assess risk of bias in observational studies.Results26 studies were identified, with results for seven specific cardiovascular disease outcomes (venous thromboembolism, myocardial infarction, stroke, angina, heart failure, arrhythmia, and peripheral vascular disease). Results suggested an increased risk of venous thromboembolism in tamoxifen users compared with both non-users and aromatase inhibitor users. Results were also consistent with a higher risk of the vascular diseases myocardial infarction and angina in aromatase inhibitor users compared with tamoxifen users, but there was also a suggestion that this may be partly driven by a protective effect of tamoxifen on these outcomes. Data were limited, and evidence was generally inconsistent for all other cardiovascular disease outcomes.ConclusionThis review has collated substantial randomised controlled trial and observational evidence on the effect of endocrine therapies on several specific cardiovascular disease outcomes including venous thromboembolism and myocardial infarction, progressing knowledge. Although the choice of aromatase inhibitor or tamoxifen will primarily be based on the effectiveness against the recurrence of breast cancer, this review shows that the individual patient’s risk of venous or arterial vascular disease should be an important secondary consideration.Systematic review registrationProspero CRD42017065944.

Major Adverse Cardiovascular Events after Treatment in Early-stage Breast Cancer Patients Receiving Hormone Therapy

“…A meta-analysis comparing tamoxifen with AIs showed that AIs were associated with a 19% increase in cardiovascular events, which may be due to the cardio-protective effect of tamoxifen 4 . However, whether tamoxifen increases the thromboembolism risk remains inconclusive 5 . In an observational study from Taiwan, female patients with breast cancer who developed acute myocardial infarction (AMI) were 1.71 times more likely to receive tamoxifen compared with those who did not develop AMI 19 .…”

Quality‐of‐life effects of screening mammography in Norway

“…We have then used a wide range of possible levels of overdiagnosis and reductions in breast cancer mortality based on randomized trials and more recent observational trials. [1][2][3][4][5][6][9][10][11][12][18][19][20]23,24 In particular, we did not assume that number of prevented breast cancer deaths were similar to the number of prevented deaths from all causes, as most others have done. 14,29,30 Some might think that 50-75% overdiagnosis is too high.…”

“…That we observed no reduction in all‐cause mortality indicates that women instead of dying of breast cancer, die of other diseases at about the same time in life compared to no screening. One likely explanation is that overdiagnosed women die of adverse effects of the treatment …”

“…One likely explanation is that overdiagnosed women die of adverse effects of the treatment. 17,18 We have evaluated mammography screening for women screened from age 50 to 69 years and followed to age 85 years, using both conventional and equity weighted sets of QALYs. We based our calculations on a range of estimates of benefits and harms of mammography screening derived from the randomized trials [1][2][3] and more recent screening programs.…”

Association of endocrine therapy with overall survival in women with hormone receptor‐positive, HER2‐negative, node‐negative breast cancer of favorable histology

“…The absolute OS benefit of 1.5% in this study is comparable to survival outcomes reported in a prior prospective study, 3 and it supports the NCCN's recommendation of considering adjuvant endocrine therapy in this patient cohort 4 . However, informed and shared decision making is encouraged for patients given the known side effects of long‐term use of endocrine therapy 6,7 . The statistically significant benefits should be weighed in the context of absolute harm to patients which includes quality‐of‐life effects.…”