Abstract
PurposeTo examine the association between statin use and risk of breast cancer recurrence in a national Danish cohort of postmenopausal breast cancer patients receiving aromatase inhibitors (AI) in the adjuvant setting.Patients and methodsWe enrolled all postmenopausal patients diagnosed with stage I–III estrogen receptor positive breast cancer during the years 2007–2017, assigned adjuvant AI treatment, and registered in both the Danish Breast Cancer Group database and the Danish Cancer Registry. We ascertained incident statin exposure (≥ 1 prescription post-diagnosis) from the Danish National Prescription Registry and modeled statins as a time-varying exposure lagged by 6 months. Follow-up began 7 months after diagnosis and continued to the first event of recurrence, death, emigration, 5 years elapsed, or 25th September 2018. We estimated incidence rates of recurrence at 5 years and used Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI), comparing statin exposure with non-exposure.ResultsWe enrolled 14,773 eligible patients. During the 5 years of follow-up, there were 32 recurrences in 3163 person-years of follow-up among statin-exposed patients, and 612 recurrences in 45,655 person-years among unexposed patients (incidence rate per 1000 person-years: 10.12 [95% CI 6.92–14.28] and 13.40 [95% CI 12.36–14.51], respectively). In multivariable models, any statin exposure was associated with a reduced rate of 5-year breast cancer recurrence (adjusted HR 0.72 [95% CI 0.50–1.04]). Considering only lipophilic statins as exposure the results were similar (adjusted HR 0.70 [95% CI 0.48–1.02]).ConclusionsStatin use was associated with a reduced risk of breast cancer recurrence among postmenopausal patients diagnosed with early stage breast cancer who received adjuvant AI therapy.
Highlights
Cholesterol-lowering medication (CLM) is frequently prescribed for prevention of cardiovascular disease [1, 2]
Since the publication of the earlier Danish study by Ahern et al investigating the association between statin use and breast cancer recurrence (BCR), statin use has increased among Danish citizens from 23.8 defined daily doses (DDD) per 1000 inhabitants per day in 2003 to 144.6 DDD/1000 inhabitants/day in 2017 [18]
This study aims to update knowledge on the association between post-diagnostic statin use and BCR in a cohort of postmenopausal patients diagnosed with early stage breast cancer, including patients diagnosed and treated in the modern era of adjuvant therapy with aromatase inhibitors (AI)
Summary
Cholesterol-lowering medication (CLM) is frequently prescribed for prevention of cardiovascular disease [1, 2]. Statins may affect the incidence or severity of other diseases (e.g., cancer) by blocking the cholesterol synthesis pathway [3]. Apart from the reduction of systemic cholesterol levels through hepatic clearance, statins inhibit the mevalonate pathway in breast cancer cells, which may lower intracellular cholesterol synthesis and lead to reduced intratumoral autocrine hormone production, since cholesterol is required for the synthesis of all steroid hormones [4]. Previous studies indicate an association between use of CLM and a reduced risk of breast cancer recurrence (BCR) [8]. Long-term post-diagnostic use of statins has been associated with reduced risk of contralateral breast cancer [9]. Among women with estrogen receptor positive (ER+) breast cancer, statin use seems to have a favorable impact on BCR and mortality when combined with adjuvant endocrine treatment [8, 10,11,12]. Given the increasing breast cancer incidence [19], any beneficial impact of statins on BCR among women treated for breast cancer could be of major value
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