SAN ANTONIO – Adjuvant aromatase inhibitor therapy in postmenopausal breast cancer survivors was associated with an increased risk of incident nonischemic cardiovascular disease, compared with tamoxifen users in a large prospective study conducted at Kaiser Permanente.
The elevation in risk was comparable in women on aromatase inhibitors (AIs) only and in those who used sequential tamoxifen followed by an AI, Reina Haque, Ph.D., reported at the San Antonio Breast Cancer Symposium.
She presented a prospective cohort study of 13,273 postmenopausal women free of known cardiovascular disease at the time of their breast cancer diagnosis during 1991-2010. Thirty-two percent of them used adjuvant tamoxifen only, 29% used an aromatase inhibitor (AI) only, 20% switched from adjuvant tamoxifen to an AI, and the rest used neither endocrine therapy.
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Reina Haque, Ph.D.
During a mean of 5.5 and maximum 22 years of prospective follow-up, 3,711 women experienced their first cardiovascular disease event. Neither rates of ischemic heart disease nor stroke differed significantly among the groups on tamoxifen, AIs, both in sequence, or neither. However, those on adjuvant AI therapy had an adjusted 26% greater risk of ‘other’ cardiovascular disease, compared with women on tamoxifen only.
The category of ‘other’ cardiovascular disease was comprised of heart failure, arrhythmia, cardiomyopathy, pericarditis, and valvular dysfunction, explained Dr. Haque, a research scientist at Kaiser Permanente of Southern California, Pasadena.
Similarly, women who switched from tamoxifen to an AI were at 28% greater risk of developing ‘other’ cardiovascular disease, compared with those on tamoxifen alone in a multivariate Cox analysis adjusted for age, demographics, comorbid conditions, cancer treatment, tumor characteristics, and use of antihypertensive agents and other cardiovascular medications.
In the subset of 7,982 patients who underwent breast irradiation, those on an adjuvant AI who received left-sided breast radiation therapy were at an adjusted 21% increased risk of all forms of cardiovascular disease – ischemic as well as other – compared with those who got left-sided breast irradiation and took tamoxifen.
As this was an observational study, the results warrant cautious interpretation, Dr. Haque said. Nevertheless, this is a study based upon 72,886 women-years of prospective follow-up and a large number of cardiovascular events, she noted.
The study was funded by the California Breast Cancer Research Program and the National Cancer Institute. Dr. Haque reported having no financial conflicts.