Comparative safety of cardiovascular medication use and breast cancer outcomes among women with early stage breast cancer

Abstract

Background Breast cancer tends to occur in an older age group of women also burdened with comorbidities such as cardiovascular disease (CVD). Numerous medications used to manage CVD (e.g., statins and antihypertensives) are hypothesized to alter breast cancer risk, but there are few studies on breast cancer outcomes. The COMBO (COmmonly used Medications and Breast Cancer Outcomes) cohort was developed to study how medications and co-morbidities influence breast cancer prognosis. Methods Cohort study among adult women, diagnosed with incident early stage breast cancer, and enrolled in an integrated health plan. Data sources included health plan administrative databases, Surveillance, Epidemiology, and End Results tumor registry, and medical records. Statins, angiotensin converting enzyme inhibitors (ACEI), beta blockers (BB), calcium blockers, and diuretics were the exposures of interest. The outcome was second breast cancer events (SBCE) defined as recurrence or second primary breast cancer. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for SBCE and components of SBCE. Results 4,216 women were followed for a median of 6.3 years, and 13.2% experienced a SBCE (first of: n=415 recurrences and n=143 second primary breast cancers). Compared to non-users, we observed an increased risk of second primary breast cancer with ACEI use (HR=1.66; 95% CI, 1.06–2.58) and an increased risk of recurrence with BB use (HR=1.29; 95% CI, 1.01–1.64). There was suggestion of a reduced risk of SBCE with statin use (HR=0.82; 95% CI, 0.62–1.08) and second primary breast cancer with BB use (HR=0.77; 95% CI, 0.50–1.19). No differences in outcomes were observed by duration of medication use. Conclusions The majority of CVD medications evaluated in this study appear safe with respect to SBCE, but ACEI and BB use warrant further evaluation. The study presented is one example of the questions that can be addressed using the COMBO cohort.

β-Blocker Use and Risk of Recurrence in Patients with Early Breast Cancer

“…Additionally, many epidemiological studies have supported the antineoplastic effects of β-blocker use [1]. However, some others revealed negative results, adding to the confusion regarding their potential benefit in cancer patients [2,3]. …”

Impact of 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol in breast cancer

“…Furthermore, statins have been shown to induce apoptosis in vitro (Spampanato et al 2012, Bjarnadottir et al 2015 and in clinical breast cancer (Garwood et al 2010, Bjarnadottir et al 2015. These data partially provide a molecular explanation for the clinical observation that statins reduce breast cancer recurrence and prolong overall survival in breast cancer patients (Ahern et al 2011, Chae et al 2011, Boudreau et al 2014, Borgquist et al 2016. Because statins effectively decrease plasma cholesterol in breast cancer patients (Garwood et al 2010, Higgins et al 2012, it has been inferred that a commensurate lowering of plasma 27HC would also occur.…”

Impact of Statin Use on Outcomes in Triple-Negative Breast Cancer

“…A population-based cohort study in Finland that included 31,236 cases of breast cancer demonstrated that breast cancer-specific mortality was approximately halved by the use of either pre-diagnostic or post-diagnostic statin use, with a dose-dependent mortality benefit seen for those taking statins prior to diagnosis [11]. Other studies have shown weak or mixed associations of statin use on breast cancer-specific mortality and breast cancer recurrence [12][13][14]. Our results highlight the potentially complex interaction between statin use, lipids, body mass index, metabolic syndrome, and possibly other heretofore unidentified factors.…”

“…Our lab and others have shown that cholesterol regulation can influence pre-clinical models of triple negative breast cancer through a PI3K/FOXO3a pathway, affecting stem cells and metastases [7][8][9]. However, clinical data on outcomes of breast cancer patients based on statin use have been mixed [10][11][12][13][14], suggesting that the interaction of statins with breast cancer stem cells may be complex and not yet adequately examined. We recently demonstrated that statins influenced disease free survival for inflammatory breast cancer (IBC) patients [15], a disease enriched in triple negative breast cancer.…”