Abstract
BackgroundPreclinical evidence suggests that statins could delay cancer progression. Previous epidemiological findings have been inconsistent and some have been limited by small sample sizes, as well as certain time-related biases. This study aimed to investigate whether breast cancer patients who were exposed to statins had reduced breast cancer-specific mortality.MethodsWe conducted a retrospective cohort study of 15,140 newly diagnosed invasive breast cancer patients diagnosed from 2009 to 2012 within the Scottish Cancer Registry. Dispensed medication usage was obtained from linkages to the Scottish Prescribing Information System and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Using time-dependent Cox regression models, hazard ratios (HR) and 95 % confidence intervals (CI) were calculated for the association between post-diagnostic exposure to statins (including simvastatin) and breast cancer-specific mortality. Adjustments were made for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of aspirin.ResultsA total of 1,190 breast cancer-specific deaths occurred up to January 2015. Overall, after adjustment for potential confounders, there was no evidence of an association between statin use and breast cancer-specific death (adjusted HR 0.93, 95 % CI 0.77, 1.12). No significant associations were observed in dose–response analyses or in analysis of all-cause mortality. For simvastatin use specifically, a weak non-significant reduction in breast cancer-specific mortality was observed compared to non-users (adjusted HR 0.89, 95 % CI 0.73, 1.08). Statin use before diagnosis was weakly associated with a reduction in breast cancer-specific mortality (adjusted HR 0.85, 95 % CI 0.74, 0.98).ConclusionOverall, we found little evidence of a protective association between post-diagnostic statin use and cancer-specific mortality in a large nation-wide cohort of breast cancer patients. These findings will help inform the decision whether to conduct randomised controlled trials of statins as an adjuvant treatment in breast cancer.
Highlights
Preclinical evidence suggests that statins could delay cancer progression
A second study included breast cancer patients diagnosed in England and we previously reported a weak non-significant 16 % reduction in breast cancer death in statin users after diagnosis which appeared slightly more marked for the highly lipophilic statin simvastatin [14]
Stage and grade were generally similar by statin use, but a slightly smaller proportion of statin users compared with non-users had poorly differentiated tumours (31 % versus 35 %, respectively)
Summary
Preclinical evidence suggests that statins could delay cancer progression. Growing laboratory evidence suggests that statins may have anti-cancer effects [1] through inhibition of cellular proliferation [2], induction of apoptosis [3] and suppression of tumour cell migration [4]. The anti-proliferative effects of statins have been demonstrated both in vitro [5] and in vivo [6], and are strong for lipophilic statins (such as simvastatin) [6]. Preclinical studies of breast cancer have indicated that the reduction in cell proliferation may be more marked in oestrogen receptor (ER) − negative cells [5], suggesting that ER-negative tumours may be more sensitive to the potential anti-cancer effects of statins. The antiproliferative and proapoptotic potential for statins have been demonstrated in breast cancer clinical trials of lipophilic [7, 8] and hydrophilic statins [9].
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