Post-diagnosis Statin Use Research Articles

Post-diagnosis statin use and survival among head and neck cancer patients: a cohort study in a universal health care system.

Little research has been conducted on the relationship between statin use and the survival of head and neck cancer patients. This study assessed whether statin use after head and neck cancer diagnosis is associated with overall survival among patients in the U.S. military health system (MHS) that provides universal health care to its beneficiaries. The study included 1842 patients with head and neck squamous cell carcinoma (HNSCC) from MHS. Statin use was extracted from the pharmacy database of the Military Health System Data Repository (MDR). Time-dependent multivariate Cox proportional hazards models were used to assess the relationship between post-diagnosis statin use and overall survival with the adjustment for potential confounders. Compared to non-users, increased post-diagnosis cumulative use of statins (per one-year of use) conferred a significant improved survival with adjusted hazard ratio (HR) of 0.70 (95% Confidence Interval, CI = 0.55 to 0.90). When analysis was stratified by status of statin use prior to HNSCC diagnosis, the HRs were 0.31 (95% CI = 0.15-0.65) and 0.81 (95% CI = 0.59-1.11) for post-diagnosis users who also used it before HNSCC diagnosis and those who only used it after the diagnosis, respectively. Prolonged statin use was associated with improved survival among HNSCC patients in MHS.

Statin use and risks of breast cancer recurrence and mortality.

Preclinical evidence suggests improved breast cancer survival associated with statin use, but findings from observational studies are conflicting and remain inconclusive. The objective of this study was to assess the association between statin use after cancer diagnosis and cancer outcomes among breast cancer patients. In this retrospective cohort study, 38,858 women aged ≥66 years who were diagnosed with localized and regional stage breast cancer from 2008 through 2017 were identified from the linked Surveillance, Epidemiology, and End Results Medicare database. Statin use was ascertained from Medicare Part D pharmacy claims data. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnosis statin use and risks of breast cancer recurrence and breast cancer-specific mortality. Over a median follow-up of 2.9 years for recurrence and 3.7 years for mortality, 1446 women experienced a recurrence, and 2215 died from breast cancer. The mean duration of post-diagnosis statin use was 2.2 years. Statin use post-diagnosis was not associated with recurrence risk (HR, 1.05; 95% CI, 0.91-1.21), but was associated with a reduced risk of cancer-specific mortality (HR, 0.85; 95% CI, 0.75-0.96). The reduction was more pronounced in women with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR, 0.71; 95% CI, 0.57-0.88). These findings suggest that post-diagnosis statin use is associated with improved cancer-specific survival in women with breast cancer and should be confirmed in randomized trials of statin therapy in breast cancer patients.

Abstract 6490: Post-diagnosis statin use and survival among head and neck cancer patients: A cohort study in the US military health system

Abstract Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal lining of the aerodigestive tract. Statin is a class of commonly prescribed medications used for treatment of high cholesterol. Studies have shown that statin exhibits anticancer effects, and the use of statin is associated with improved survival of common cancers, such as prostate, breast and colorectal cancers. However, few research has been conducted on statin use in relation to the survival of HNSCC. This study assessed whether statin use after HNSCC diagnosis is associated with overall survival among patients with HNSCC in the U.S. military health system (MHS). The MHS provides universal health care to its beneficiaries with no or little out-of-pocket cost, thus a study in the MHS reduces the effects of prescription drug access related to patients’ insurance coverage, race and socio-economic status. This study included 1,842 adult patients (18 or older) with histologically confirmed HNSCC identified from the MilCanEpi database which contains information from the Department of Defense’s Central Cancer Registry (CCR) and the Military Health System Data Repository (MDR). Patients were diagnosed between January 1, 2002 and December 31, 2014 and followed up through December 31, 2015. Statin use was extracted from the MDR pharmacy data containing prescription records from all sources. Among the 1,842 patients, 389 patients used statin after HNSCC diagnosis. Time-dependent multivariate Cox proportional hazards models were used to assess the relationship between post-diagnosis statin use and overall survival, reducing the potential effects of immortal time bias. Statistical adjustment was made for covariables including age, sex, race, Hispanic ethnicity, active-duty status, history of cardiovascular diseases, Charlson comorbidity index, baseline statin use, tumor site, tumor stage and cancer treatments. Increased post-diagnosis cumulative use of statin (per one-year of use) conferred a significant improved survival with adjusted hazard ratio (HR) of 0.70 (95% CI=0.55 to 0.90). When analysis was stratified by status of statin use prior to HNSCC diagnosis, the HRs were 0.36 (95% CI=0.19-0.69) and 0.81 (95% CI=0.59-1.11) for those who used and did not use it before the diagnosis, respectively. While the numbers of patients for each group of this stratified analysis were not large, our study suggest that prolonged duration of Statinuse may be associated with improved survival among HNSCC patients. Future research with a larger number of patients is warranted. Disclaimer: The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views, opinions, or policies of the USUHS, HJF, the DoD or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. Citation Format: Jie Lin, Craig D. Shriver, Kangmin Zhu. Post-diagnosis statin use and survival among head and neck cancer patients: A cohort study in the US military health system. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6490.

Statin use and survival in 16 098 patients with non-Hodgkin lymphoma or chronic lymphocytic leukaemia treated in the rituximab era.

Statin use has been associated with reduced mortality from several cancers but also suggested, invitro, to diminish the effectiveness of lymphoma treatments including rituximab. The present study aimed to assess the association of statin use with mortality in patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). We identified all incident NHLs and CLLs in Sweden from 2007 to 2013 with subtype information in the Swedish Lymphoma and Cancer Registers. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of pre- or post-diagnosis statin use (yes/no, intensity) with lymphoma-specific, cardiovascular, or all-cause mortality; and for follicular lymphoma (FL) by initial treatment strategy (active/watch-and-wait). Among 16 098 incident NHL/CLL patients, 20% used statins at diagnosis. Pre- and post-diagnosis statin use, and statin intensity were not consistently associated with any mortality outcome in patients with NHL, overall or for any subtype. For actively treated patients with FL, statin use did not appear to increase lymphoma-specific mortality (vs. non-users, HR [95% CI]after diagnosis 0·87 [0·45-1·67]). For CLL, statin use was associated with all-cause and cardiovascular but not consistently with lymphoma-specific mortality. In conclusion, statin use was not associated with improved lymphoma survival but appears safe to use during lymphoma treatment.

Use of Statin Medications Following Diagnosis in Relation to Survival among Women with Ovarian Cancer.

It has been suggested that the likelihood of survival among women with ovarian cancer could be increased by postdiagnosis statin use. This study examines the potential association between postdiagnosis statin use and cancer-specific mortality among women with ovarian cancer. This cohort study used SEER-Medicare data on women ≥66 years of age diagnosed with ovarian cancer during 2007 to 2012 who were enrolled in Medicare parts A, B, and D during the year after diagnosis. Statin use was defined as two or more fills for a statin during the year after diagnosis. Ovarian cancer-specific death was assessed starting 1 year after diagnosis. Marginal structural Cox models were used, adjusting for the inverse probability of treatment weighting and censoring weighting. Treatment weights and censoring weights were calculated using logistic regression models with a priori-defined covariates. Among 2,195 women with ovarian cancer, 489 (22%) used statins within 1 year after their diagnosis. Over a mean follow-up of 2.2 years, 796 (36%) women died from ovarian cancer. The adjusted HR for ovarian cancer mortality comparing statin users to nonusers was 0.74 (95% confidence interval, 0.61-0.91). Findings from this and prior work suggest statin use following a diagnosis with ovarian cancer is associated with a lower risk of cancer death. Because, in most women, statin administration has limited side effects, a randomized trial of statins among patients with ovarian cancer may be warranted.

Highlights of This Issue

It has been suggested that the likelihood of survival among women with ovarian cancer could be increased by post-diagnosis statin use. This study, by Harding and colleagues, examines the potential association between post-diagnosis statin use and cancer-specific mortality among women with ovarian cancer. Using SEER-Medicare data on women 66+ years of age diagnosed with ovarian cancer during 2007-2012 who were enrolled in Medicare parts A, B and D during the year after diagnosis, the finding of this cohort study (and prior work) suggest statin use following a diagnosis with ovarian cancer is associated with a lower risk of cancer death.Shiftwork exerts its carcinogenic activity largely via nightly light exposure and resulting alterations in circadian rhythms. Razavi and colleagues followed 130 participants of the Nurses' Health Study during their actual shiftwork in a comprehensive field study, collecting over 3 days 24/7 light measurements via a light-meter worn close to the eye, and 15 urine specimens for detailed melatonin measurements. They verified alterations in melatonin rhythms during nightwork, showing that these appeared gravest when work-hours were at odds with preferred sleep-timing i.e. morning persons working nightshifts, or evening persons working morning/day shifts. This work represents an important step towards individualized risk assessment/cancer prevention among night workers.Population-level awareness of the association between alcohol and cancer is understudied in the U.S., as are personal characteristics associated with awareness. In a nationally representative survey, only 38% of U.S. residents acknowledged that drinking too much alcohol can increase risk of cancer, and 36% were uncertain (i.e., reported “don't know”). People who had ever looked up information about cancer had higher odds of awareness; people with lower levels of health self-efficacy had higher odds of uncertainty. This study by Wiseman and Klein supports that broad-reaching public health campaigns are warranted to increase awareness of the association between alcohol and cancer in the U.S.Experiencing financial hardship (e.g., borrowing, debt, using assets, experiencing a decrease in income) due to cancer is associated with lower health-related quality of life among cancer survivors, but the mechanisms or actionable targets for intervention are not clear. In this study, Hastert and colleagues, use data from the Detroit Research on Cancer Survivors (ROCS) pilot cohort to assess the role that limiting care due to cost plays in this association, finding that limiting care explained 40% of the association between financial hardship and health-related quality of life overall, and 50% among African American survivors. These findings suggest that policies and interventions to ensure cancer survivors can access necessary treatment without financial hardship could improve health-related quality of life, particularly for African American survivors.

Statin Use After Diagnosis of Hepatocellular Carcinoma Is Associated With Decreased Mortality

Statin use is associated with a lower risk of developing hepatocellular carcinoma (HCC). However, it is unclear whether postdiagnosis statin use is associated with a reduced risk of death in patients with HCC. We performed a retrospective analysis of data from 15,422 patients with HCC in the Veterans Administration Central Cancer Registry, diagnosed from 2002 through 2016. We identified statin prescriptions that were filled before and after the cancer diagnosis and used time-dependent Cox regression models to calculate adjusted hazard ratios (HRs) and 95% CIs for risk of death. We used a time-varying exposure to avoid immortal time bias, and a 3-month lag (following up patients from 3 months after the cancer diagnosis) to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between date of cancer diagnosis and start of follow-up evaluation. Statin use after diagnosis was recorded for 14.9% of patients with HCC. We found that postdiagnosis statin use was associated with a decreased risk of cancer-specific death (adjusted HR, 0.85; 95% CI, 0.77-0.93) and all-cause mortality (HR, 0.89; 95% CI, 0.83-0.95). The magnitudes of these inverse associations were consistent for patients who used high or low doses of statins, and the inverse associations remained across a range of lag periods (from 0 months to 12 months after HCC diagnosis). We found no evidence for effect modification by prediagnosis statin use, or by presentation- or treatment-related factors, and no independent association with prediagnosis statin use. In a retrospective analysis of data from veterans with HCC, use of statins (high or low doses) after a diagnosis of HCC was associated with reduced mortality.

Statin use and risk of contralateral breast cancer: a nationwide cohort study

BackgroundStatins have demonstrated antineoplastic effects in breast cancer cell lines, particularly in oestrogen receptor (ER)-negative cell lines. However, epidemiological studies have not supported a preventive effect of statin use against breast cancer. Therefore, we examined the association between statin use and contralateral breast cancer (CBC) risk among women with breast cancer.MethodsWe identified 52,723 women with non-metastatic breast cancer during 1996–2012 from the Danish Breast Cancer Group database. We defined time-varying post-diagnosis statin use as minimum two prescriptions lagged by 1 year. Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with statin use.ResultsStatin use was associated with a lower CBC risk (HR = 0.88; 95% CI = 0.73–1.05). The inverse association was strongest for long-term use overall (HR = 0.64; 95% CI = 0.43–0.96), although the HR specifically for long-term consistent use and high-intensity use approached unity. Among ER-negative breast cancer patients, statin use was associated with a CBC risk reduction (HR = 0.67; 95% CI = 0.45–1.00).ConclusionsWe found some indication that statins reduce the risk of CBC. Further evaluations are needed to disentangle the equivocal results for long-term use and to establish if ER-negative breast cancer patients may benefit most from statin use.

Statin use and mortality among endometrial cancer patients: a Danish nationwide cohort study.

Statin use has been linked to improved prognosis of some cancer types, however, for endometrial cancer, the results are equivocal. We therefore examined the effect of statin use on endometrial cancer mortality. From the Danish Cancer Registry, we identified all women in Denmark aged 30-84 years with primary endometrial cancer during 2000-2012. Data on drug use, mortality outcomes and potential confounders were retrieved from nationwide registries. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for endometrial cancer-specific and other-cause mortality associated with statin use. Among 6,694 endometrial cancer patients, 753 died from endometrial cancer and 765 from other causes during a median follow-up of 4.5 year (interquartile range: 1.9-8.1). We observed an inverse association between time-varying postdiagnosis statin use (≥2 prescriptions) and endometrial cancer mortality (HR: 0.61, 95% CI: 0.48-0.77) compared to non-use (<2 prescriptions). The associations did not differ substantially by intensity or cumulative amount of statin use. In secondary analyses including prediagnosis statin use, we observed reduced mortality among both continuing (pre- and postdiagnosis) users (HR 0.70, 95% CI 0.53-0.92) and new (postdiagnosis only) users (HR 0.43, 95% CI 0.29-0.65) compared to "never users." In sensitivity analyses with fixed exposure periods after the endometrial cancer diagnosis, the inverse association was more pronounced more than 5 years after the diagnosis. Our findings suggest that statin use may be associated with improved survival in endometrial cancer patients.

Postdiagnosis Statin Use and Mortality in Danish Patients With Prostate Cancer.

Purpose Increasing evidence indicates that statin use may reduce mortality from prostate cancer. In this work, we examined whether postdiagnosis statin use was associated with reduced cancer-specific mortality or all-cause mortality among patients with prostate cancer in Denmark. Material and Methods From nationwide Danish registries, we identified all patients with incident prostate adenocarcinoma from 1998 to 2011 and retrieved data on tumor and patient characteristics, drug use, and primary treatment. We defined postdiagnosis use (two or more prescriptions) of statins as a time-varying covariate with 1-year lag. Cox proportional hazards regression models used to compute hazard ratios (HRs) for prostate cancer-specific mortality and all-cause mortality through 2013 associated with postdiagnosis statin use. In secondary and sensitivity analyses, we assessed statin use within exposure periods of 1 year or 5 years after prostate cancer diagnosis and evaluated the influence of prediagnosis statin use. Results Among 31,790 patients, 7,365 died of prostate cancer and 11,811 died from other causes during a median follow-up of 2.8 years (interquartile range, 1.3 to 5.1 years) from 1 year after diagnosis. Postdiagnosis statin use was associated with adjusted HRs of 0.83 (95% CI, 0.77 to 0.89) for prostate cancer mortality and 0.81 (95% CI, 0.76 to 0.85) for all-cause mortality. Similar results were observed in 1-year and 5-year sensitivity analyses. No substantial effect measure modification was found with estimated dose or type of statin, clinical stage, Gleason score, or with prediagnosis statin use; however, patients who were diagnosed early in the study period or who underwent radical prostatectomy or endocrine therapy exhibited slightly lower HRs for prostate cancer mortality with postdiagnosis statin use than did those in the overall analyses. Conclusion Postdiagnosis statin use was associated with reduced mortality from prostate cancer; however, it remains to be established whether this association is causal.

Statin use and breast cancer survival and risk: a systematic review and meta-analysis.

The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54-0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53-0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43-0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48-1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings.

Prognostic Significance of Statin Use in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Statin intake has been reported to reduce the risk of several malignancies beyond its cholesterol-lowering effects. However, little is known regarding the survival benefit of statins for patients with colorectal cancer (CRC).We conducted a systematic literature search of multiple databases for studies published before November 2014, which investigated associations between statin intake and CRC prognosis. Meta-analysis was performed using random-effects model. The primary outcomes of interest were all-cause mortality (ACM) and cancer-specific mortality (CSM).Ten studies involving 76,851 patients were eligible for this meta-analysis, with 7 studies investigating prediagnosis statin use and 5 studies reporting postdiagnosis statin use. Prediagnosis statin use was associated with reduced ACM (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.61-0.88, P = 0.001) and CSM (HR 0.80, 95% CI 0.77-0.84, P < 0.001) for patients with CRC. This effect persisted when stratified by tumor site and in studies adjusted by nonsteroidal anti-inflammatory drug use. In addition, postdiagnosis statin use was associated with decreased CSM (HR 0.70, 95% CI 0.60-0.82, P < 0.001). However, we did not note reduced ACM for postdiagnosis statin use (HR 0.93, 95% CI 0.68-1.27, P = 0.639). There appeared to be an association between postdiagnosis statin use and increased ACM in KRAS-mutated CRC.Our findings provide evidence that prediagnosis statin therapy was associated with reduced ACM and CSM in CRC patients; postdiagnosis statin therapy indicated decreased CSM. However, findings may not apply to patients with postdiagnosis statin therapy for ACM. Further studies are warranted to determine the relation between statin dose and duration on CRC survival.

Relationship between the use of statins and patient survival in colorectal cancer: a systematic review and meta-analysis.

BackgroundStudies have indicated that statins influence the risks and mortality rates of several types of solid tumors. However, the association between statin use and survival in patients with colorectal cancer (CRC) remains unclear.MethodsWe searched the PubMed and Embase databases for relevant studies published up to September 2014 that assessed statin use and CRC prognosis. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). The secondary outcomes were disease-free survival (DFS) and recurrence-free survival (RFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled with Mantel–Haenszel random-effect modeling. All statistical tests were two-sided.ResultsFour studies on post-diagnosis statin therapy and five studies on pre-diagnosis statin use were included in our meta-analysis of 70,608 patients. Compared with the non-users, the patients with post-diagnosis statin use gained survival benefits for OS (HR 0.76; 95% CI: 0.68 to 0.85, P<0.001) and CSS (HR 0.70; 95% CI: 0.60 to 0.81, P<0.001). In addition, we observed that pre-diagnosis statin use prolonged the survival of patients with CRC for OS (HR 0.70; 95% CI: 0.54 to 0.91, P=0.007) and CSS (HR 0.80; 95% CI: 0.74 to 0.86, P<0.001). However, we did not observe a survival benefit for DFS (HR 1.13; 95% CI: 0.78 to 1.62, P=0.514) or RFS (HR 0.98; 95% CI: 0.36 to 2.70, P=0.975) in the CRC patients with post-diagnosis statin use.ConclusionsStatin use before or after cancer diagnosis is related to reductions in overall and cancer-specific mortality in colorectal cancer survivors.

Abstract P6-09-03: Improved clinical outcomes associated with statin use during adjuvant chemotherapy in patients with HER2+ non-metastatic breast cancer

Abstract Background Statins are established as first line therapy in patients with hypercholesterolemia and are thought to have pleiotropic effects including inhibition of signaling pathways known to drive cell proliferation and survival responses. Numerous preclinical and observational studies have demonstrated activity and improved outcomes in breast cancer patients who received statins, particularly lipophilic statins, as part of their adjuvant therapy. In the Life After Cancer Epidemiology (LACE) Study, 1,945 early-stage breast cancer survivors were shown to have a 33% decreased risk of breast cancer recurrence with post-diagnosis statin use, an effect that was magnified with increasing duration of statin use. We hypothesized that statin use concurrent with trastuzumab based chemotherapy in patients treated for non-metastatic HER2 positive breast cancer would be associated with improved outcomes. Methods We performed a retrospective review of all patients (n = 300) with HER2+ breast cancer who received trastuzumab from 2006-2012 at UM/SCCC. We identified two groups of patients for comparison - those who received statins (ST) during adjuvant chemotherapy (n = 45) or no statins during chemotherapy (NST) during adjuvant chemotherapy (n = 200). Patients with unclear documentation of concurrent statin use, men, patients with de-novo-metastatic breast cancer or prior primary cancer, bilateral breast cancers, and patients without follow-up were excluded. 5-year disease free (DFS) and overall survival (OS) were calculated. A univariate analysis was performed. Multivariate analysis for time-to-event data, using the Cox and extended Cox regression model will be performed and reported. Results The median age at diagnosis was 58 and 48, in the ST and NST groups, respectively. The most commonly used statin was lipophilic simvastatin (34.1%). The average baseline and post chemotherapy total cholesterol level in the ST group was 200.8 and 218.1mg/dL, respectively. Descriptive characteristics of the ST and NST groups respectively are as follows: postmenopausal (77.8% vs. 43.5%) tumor size &amp;lt;2cm (48.9% vs. 41.0%), node-negative disease (40.0% vs. 40.0%), HR+ status (64.4% vs. 60.5%), diabetes mellitus (26.7% vs. 9.0%), baseline BMI &amp;gt;30 (40.0% vs. 27.0%), and concomitant metformin (28.9% vs. 11.5%). The NST group was more likely to have a reduction of greater than 10% in their EF (9.0% vs. 6.7%). At a median follow-up of 32 and 26 months, the estimated 5-year DFS was significantly improved in the ST group (81.8% vs. 51.5%, p = 0.046). Meanwhile, the estimated 5-year OS was not significantly different between both groups (93.4% vs. 91.6%, p = 0.121). Metformin was not associated with a significant improvement in DFS or OS. Conclusion Our study demonstrated that statin use concurrent with trastuzumab-based chemotherapy for non-metastatic HER2 breast cancer was associated with improved estimated 5-year DFS, but not OS. The retrospective nature of our study does not allow for a definitive answer but further research needs to be done to define the role of statins in HER2+ breast cancer treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-03.

Abstract 4678: Post-diagnosis use of lipophilic statins and breast cancer recurrence: A Danish nationwide cohort study

Abstract Statins may affect non-cardiovascular endpoints, including cancer incidence and survival. These effects may depend on the solubility of the specific medicine. Our objective was to measure the association between post-diagnosis lipophilic and hydrophilic statin use and recurrence among non-metastatic breast cancer patients. We ascertained incident cases of stage I-III invasive breast cancer diagnosed in Denmark between 1996 and 2006 from the Danish Breast Cancer Cooperative Group registry, and linked these records to the Register of Medicinal Products (RMP), which automatically logs pharmacy transactions in Denmark. We determined statin prescriptions filled by cohort members by searching the RMP for appropriate ATC codes. Statins were classified by solubility (Table 1) and exposure status was updated yearly. Follow-up began upon completion of primary therapy and continued until the first of breast cancer recurrence, death from any cause, emigration from Denmark, or the end of 2006. Associations were estimated with time-dependent crude and multivariate Cox regression models. We enrolled 18,769 breast cancer patients, with a median follow-up of 6.2 years. Of the 3,282 women ever prescribed a statin after diagnosis, 2,518 were exclusively prescribed lipophilic statins and 210 were exclusively prescribed hydrophilic statins. Crude and multivariate models yielded similar estimates. Lipophilic (but not hydrophilic) statin use was associated with a reduced rate of breast cancer recurrence (compared with no statin use: multivariate HR for lipophilic statin use = 0.65, 95% CI: 0.55, 0.76; multivariate HR for hydrophilic statin use = 0.89, 95% CI: 0.61, 1.3). Associations were similar when estimated in the subset of women with no pre-diagnosis statin exposure. In this population-based prospective cohort study with complete information on prognostic and treatment variables, breast cancer patients who took lipophilic statins had a reduced rate of breast cancer recurrence. (a) Hazard ratios adjusted for age, menopausal status, tumor stage, ER status, adjuvant hormonal therapy, type of surgery, comorbidity, and co-prescription of aspirin. Estimates were similar in models further adjusted for chemotherapy, type of surgery, receipt of radiotherapy, and co-prescription of hormone replacement therapy, NSAIDs, anticoagulants and ACE inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4678. doi:10.1158/1538-7445.AM2011-4678

Post-diagnosis statin use and breast recurrence sites in early stage breast cancer survivors

To the Editor, We read the article by Kwan et al. [1] in which they showed an inverse association between post-diagnosis, lipophilic statin use and risk of breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors. However, information related to the specific recurrence sites were not discussed in their study. Evidence from animal models suggests that activation of osteoclastmediated bone resorption is an essential step in the process of bone metastasis [2]. Bisphosphonates are class of agents most frequently used to reduce skeletal-related events in patients with bone metastases by inhibiting osteoclast activity through inhibition of mevolanate pathway. Relationship between statins and nitrogen-containing bisphosphonates has been established. Both drugs interfere with the same metabolic pathway. Both exert their activity in the mevalonate pathway This pathway leads to cholesterol synthesis and to protein prenylation, adding a lipid chain to transpeptidases such as Ras and Ras-like transpeptidases in the osteoclast membrane which in turn leads to activation of osteoclasts [3]. Furthermore, some studies showed that bisphosphonates might reduce or prevent the incidence of bone metastases by inhibiting tumour-induced osteoclastic resorption of bone when they are used as an adjuvant treatment of breast cancer [4, 5]. Therefore, we suggest that post-diagnosis, lipophilic statin use may reduce bone metastases more than other recurrence sites in early stage breast cancer survivors.

Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors

We examined the association between post-diagnosis statin use (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] inhibitors) and risk of breast cancer recurrence. The study included 1945 early stage breast cancer survivors participating in the Life After Cancer Epidemiology (LACE) Study. Women who were diagnosed from 1997 to 2000 and identified from the Kaiser Permanente Northern California (KPNC) Cancer Registry entered the cohort on average 2 years post-diagnosis. Information on statin use was obtained from the KPNC pharmacy database. A total of 210 breast cancer recurrences were reported and verified by medical record review. Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). The mean duration of statin use in the cohort among those who initiated use post-diagnosis was 1.96 years, and lipophilic statins were mainly used (97.8%). Starting statins after diagnosis was suggestive of a decreased risk of breast cancer recurrence (RR = 0.67; 95% CI: 0.39-1.13). Risk of recurrence decreased with increasing duration of statin use after diagnosis (p linear trend = 0.02). Our findings provide initial support for an inverse association between post-diagnosis, lipophilic statin use and risk of breast cancer recurrence.