Statin use and breast cancer risk in a large population-based setting.

BACKGROUND: Mechanistic studies suggest that 3-hydroxy-3-methylglutaryl CoA inhibitors (statins) reduce the risk of breast cancer. Observational studies offer mixed results. METHODS: To evaluate the relation between statin use and breast cancer risk, we conducted a cohort study among women ages 45 to 89 years within an integrated health care delivery system. Information on statin use and covariates were obtained from automated databases. We identified breast cancer cases through the Surveillance, Epidemiology, and End Results registry. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for invasive breast cancer among statin users compared with nonusers. RESULTS: Among 92,788 women studied from 1990 to 2004, median follow-up time was 6.4 years, and 2,707 breast cancer cases were identified. During the study period, 7.4% of women used statins for at least 1 year, and the median duration of use was 3.1 years. We found no difference in breast cancer risk among statin users (HR, 1.07; 95% CI, 0.88-1.29) compared with nonusers. Risk of breast cancer did not differ by duration of use (1-2.9, 3-4.9, or >or=5 years) or hydrophobic statin use. We found a suggestive increased risk of breast cancer among statin users of >or=5 years (HR, 1.27; 95% CI, 0.89-1.81 for any statins and HR, 1.47; 95% CI, 0.89-2.44 for hydrophobic statins) and of estrogen receptor-negative tumors with increasing duration of statin use (1-2.9 years: HR, 1.33; 95% CI, 0.64-2.77; 3-4.9 years: HR, 1.68; 95% CI, 0.72-3.92; >or=5 years: HR, 1.81; 95% CI, 0.75-4.36). CONCLUSION: This study does not support an association between statin use and breast cancer risk.     

Statin use and female reproductive organ cancer risk in a large population-based setting

Objective  Statins are an effective and commonly used cholesterol-lowering medication class, but their hypothesized effects on cancer risk remain uncertain. We evaluated the association between statin use and endometrial as well as ovarian cancer risks. Methods  We conducted a retrospective study with two cohorts of women aged 45–89 years during 1990–2004 within an integrated healthcare delivery system. Information on statin use and covariates were obtained from automated databases. We identified cancer cases through the Surveillance, Epidemiology, and End Results registry. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident invasive endometrial and ovarian cancers among statin users compared to nonusers. Results  Women were followed for a median of about six years. Among 73,336 women studied, 568 endometrial cancer cases were identified. During the study period, 6% of women used statins for at least one year and the median duration of use was 3.1 years. Although not statistically significant, we found a reduction in endometrial cancer risk among statin users (HR = 0.67; 95% CI: 0.39–1.17) compared to nonusers. We identified 326 ovarian cancer cases in a cohort of 93,619 women. There was also a nonsignificant decrease in ovarian cancer risk among statin users (HR = 0.69; 95% CI: 0.32–1.49). Conclusion  Our study does not support an association between statin use and endometrial as well as ovarian cancers, but a reduced risk cannot be ruled out.     

Statin use and prostate cancer risk in a large population-based setting

BACKGROUND: Statins are a commonly used cholesterol-lowering drug, which also have the potential to affect cancer risk and progression. Results from previous studies offer mixed conclusions. METHODS: To evaluate the relation between statin use and prostate cancer risk, we conducted a retrospective cohort study during 1 January 1990 to 31 August 2005 among men 45-79 years receiving care within Group Health, an integrated healthcare delivery system. Information on statin use and covariates were obtained from health plan databases. We identified incident prostate cancer cases through the Surveillance, Epidemiology, and End Results cancer registry. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for prostate cancer among statin users compared to non-users. RESULTS: Among 83,372 men studied, median follow-up time was 5.7 years and 2,532 prostate cancer cases were identified. About 14.4% used statins over the study period and median duration of use was 3.3 years. Compared to non-users, hydrophobic statin users had a reduced risk of prostate cancer (HR = 0.79; 95% CI, 0.66-0.94), and results are suggestive of a reduced risk among ever users of statins (HR = 0.88; 95% CI, 0.76-1.02) and hydrophilic statin users (HR = 0.67; 95% CI, 0.33-1.34). There was no trend in risk by duration of statin use, and no association between statin use and cancer aggressiveness, stage, or grade. CONCLUSION: Overall, this study does not support an associated between statin use and prostate cancer but a reduced risk cannot be ruled out.     

Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort

HMG-coA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use. However, little is known about the association between long-term statin use and incidence of most types of cancers. We examined the association between long-term use of cholesterol-lowering drugs, predominantly statins, and the incidence of ten common cancers, as well as overall cancer incidence, among 133,255 participants (60,059 men and 73,196 women) in the Cancer Prevention Study II Nutrition Cohort during the period from 1997 to 2007. Multivariate Cox proportional hazards regression was used to estimate relative risks (RR). Current use status and duration of use were updated during follow-up using information from biennial follow-up questionnaires. Current use of cholesterol-lowering drugs for five or more years was not associated with overall cancer incidence (RR = 0.97, 95% CI = 0.92-1.03), or incidence of prostate, breast, colorectal, lung, bladder, renal cell, or pancreatic cancer but was associated with lower risk of melanoma (RR = 0.79, 95% CI = 0.66-0.96), endometrial cancer (RR = 0.65, 95% CI = 0.45-0.94), and non-Hodgkin lymphoma (NHL; RR = 0.74, 95% CI = 0.62-0.89). These results suggest that long-term use of statins is unlikely to substantially increase or decrease overall cancer risk. However, associations between long-term statin use and risk of endometrial cancer, melanoma, and NHL deserve further investigation.     

Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age

Rapid increases in the incidence of adenocarcinoma of the esophagus have been reported among white men. We further explored the temporal patterns of this disease among white individuals by sex, stage, and age by use of data from the Surveillance, Epidemiology, and End Results program. We identified 22,759 patients from January 1, 1975, through December 31, 2004, with esophageal cancer, of whom 9526 were diagnosed with adenocarcinoma of the esophagus. Among white men, increases in the incidence of esophageal cancer were largely attributed to a 463% increase in the incidence of adenocarcinoma over this time period, from 1.01 per 100,000 person-years (95% confidence interval [CI] = 0.90 to 1.13) in 1975-1979 to 5.69 per 100,000 person-years (95% CI = 5.47 to 5.91) in 2000-2004. A similar rapid increase was also apparent among white women, among whom the adenocarcinoma rate increased 335%, from 0.17 (95% CI = 0.13 to 0.21) to 0.74 per 100,000 person-years (95% CI = 0.67 to 0.81), over the same time period. Adenocarcinoma rates rose among white men and women in all stage and age groups, indicating that these increases are real and not an artifact of surveillance.     

Cancer risk in women prenatally exposed to diethylstilbestrol

Prenatal diethylstilbestrol (DES) exposure is associated with excess risks of clear cell adenocarcinoma (CCA), and breast cancer in older women. Whether overall cancer risk is also elevated is unclear. Total and site-specific cancer risks were evaluated in the DES Combined Cohort Follow-up Study using age- and calendar-year specific standardized incidence rate ratios (SIR), and age-adjusted incidence rate ratios (RR) comparing DES exposed and unexposed women. A total of 143 and 49 cancer cases occurred in 97,831 and 34,810 person-years among the exposed and unexposed, respectively. There was no overall excess risk among exposed women when compared with external rates (SIR 1.01; 95% confidence interval [CI] 0.86-1.2). The overall RR comparing exposed with unexposed women was 1.32 (95% CI 0.94-1.8). Breast cancer risk was elevated only among women over 40 years (RR 1.83; 95% CI 1.1-3.2). The CCA SIR among exposed women was nearly 40, and the estimated attack rate through age 39 was 1.6/1,000 women. CCA incidence decreased by over 80% after age 25 when compared with 20-24 years. Excluding CCA and breast cancer, the overall RR was 1.21 (95% CI 0.74-2.0). DES was not associated with excess risks of either endometrial or ovarian cancer. These data suggest that the DES associated increase in CCA incidence remains elevated through the reproductive years. There was no consistent evidence of risk excesses for cancers other than CCA, and breast cancer in older women. Given that the population is still young, continued follow-up is necessary to assess the overall carcinogenic impact of prenatal DES exposure.     

Prospective analysis of association between use of statins and melanoma risk in the Women's Health Initiative

BACKGROUND:

Melanoma is the most lethal form of skin cancer, with an estimated 68,130 new cases and 8700 deaths in the United States in 2010. The increasing incidence and high death rate associated with metastatic disease support the need to focus on prevention. The authors used data from the Women's Health Initiative (WHI) to assess whether 3‐hydroxy‐3 methylglutaryl coenzyme A inhibitors (statins) are associated with a decreased risk of melanoma.

METHODS:

The study population consisted of 119,726 postmenopausal white women, in which 1099 cases of malignant melanoma were identified over an average (±standard deviation) of 11.6 ± 3.2 years. All diagnoses were confirmed by medical record review and pathology reports. Information on statin use was collected at baseline and during follow‐up. Self‐administered and interview‐administered questionnaires were used to collect information on other risk factors. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses investigated the association of any statin use, type, potency, lipophilic status, and duration of use with melanoma.

RESULTS:

Statins were used by 8824 women (7.4%) at baseline. The annualized rate of melanoma was 0.09% among statin users and 0.09% among nonusers The multivariable adjusted HR for statin users compared with nonusers was 1.14 (95% CI, 0.91‐1.43). There were no significant differences in risk based on statin type, potency, category, duration, or in time‐dependent models.

CONCLUSIONS:

There was no significant association between statin use and melanoma risk among postmenopausal women in the WHI. Cancer 2012. © 2012 American Cancer Society.     

Stroke as a late treatment effect of Hodgkin's Disease: a report from the Childhood Cancer Survivor Study.

PURPOSE: The objectives of this report are to examine the incidence of and risk factors for stroke among childhood Hodgkin's disease (HD) survivors. PATIENTS AND METHODS: The Childhood Cancer Survivor Study is a multi-institutional cohort study of more than 5-year cancer survivors diagnosed between 1970 and 1986 and a sibling comparison group. Incidence rates of stroke among HD survivors (n = 1,926) and siblings (n = 3,846) were calculated and compared. Cox proportional hazards models were used to estimate the hazard ratios, reported as relative risks (RR), of developing stroke between HD survivors and siblings. RESULTS: Nine siblings reported a stroke, for an incidence of 8.00 per 100,000 person-years (95% CI, 3.85 to 14.43 per 100,000 person-years). Twenty-four HD survivors reported a stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100,000 person-years (95% CI, 54.5 to 121.7 per 100,000 person-years). The RR of stroke among HD survivors was 4.32 (95% CI, 2.01 to 9.29; P = .0002). All 24 survivors received mantle radiation exposure (median dose, 40 Gy). The incidence of late-occurring stroke among HD survivors treated with mantle radiation was 109.8 per 100,000 person-years (95% CI, 70.8 to 161.1 per 100,000 person-years). The RR of late-occurring stroke among HD survivors treated with mantle radiation was 5.62 (95% CI, 2.59 to 12.25; P < .0001). CONCLUSION: Survivors of childhood HD are at increased risk of stroke. Mantle radiation exposure is strongly associated with subsequent stroke. Potential mechanisms may include carotid artery disease or cardiac valvular disease.     

The influence of statin use on breast density.

OBJECTIVE: To evaluate if 3-hydroxy-3-methylglutaryl CoA reductase reductase inhibitor use (statins) alters mammography measured breast density. METHODS: Cohort study of women ages 50 to 80 years with two mammography screenings. Changes in BI-RADS breast density between screenings was compared for nonusers, initiators, discontinuers, continuers, and any users of statins. RESULTS: Statin use was not associated with increases or decreases in breast density compared with nonusers after adjusting for age, body mass index, change in body mass index, hormone therapy use, and time between screenings. Cumulative days of statin use during the year before screening was not associated with changes in breast density in any of the groups of statin users. When hormone therapy users were excluded, any statin use was associated with an increase in breast density compared with nonusers (odds ratio, 1.2; 95% confidence interval, 1.0-1.5). CONCLUSIONS: We found no association between statin use and change in breast density in general, but statin use may be associated with increases in breast density among nonusers of hormone therapy.     

Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality

BACKGROUND: Hormone replacement therapy (HRT) is typically avoided for women with a history of breast cancer because of concerns that estrogen will stimulate recurrence. In this study, we sought to evaluate the impact of HRT on recurrence and mortality after a diagnosis of breast cancer. METHODS: Data were assembled from 2755 women aged 35-74 years who were diagnosed with incident invasive breast cancer while they were enrolled in a large health maintenance organization from 1977 through 1994. Pharmacy data identified 174 users of HRT after diagnosis. Each HRT user was matched to four randomly selected nonusers of HRT with similar age, disease stage, and year of diagnosis. Women in the analysis were recurrence free at HRT initiation or the equivalent time since diagnosis. Rates of recurrence and death through 1996 were calculated. Adjusted relative risks were estimated by use of the Cox regression model. All statistical tests were two-sided. RESULTS: The rate of breast cancer recurrence was 17 per 1000 person-years in women who used HRT after diagnosis and 30 per 1000 person-years in nonusers (adjusted relative risk for users compared with nonusers = 0.50; 95% confidence interval [CI] = 0.30 to 0.85). Breast cancer mortality rates were five per 1000 person-years in HRT users and 15 per 1000 person-years in nonusers (adjusted relative risk = 0.34; 95% CI = 0.13 to 0.91). Total mortality rates were 16 per 1000 person-years in HRT users and 30 per 1000 person-years in nonusers (adjusted relative risk = 0.48; 95% CI = 0.29 to 0.78). The relatively low rates of recurrence and death were observed in women who used any type of HRT (oral only = 41% of HRT users; vaginal only = 43%; both oral and vaginal = 16%). No trend toward lower relative risks was observed with increased dose. CONCLUSION: We observed lower risks of recurrence and mortality in women who used HRT after breast cancer diagnosis than in women who did not. Although residual confounding may exist, the results suggest that HRT after breast cancer has no adverse impact on recurrence and mortality.     

Incidence trends of adult primary intracerebral tumors in four Nordic countries

Brain tumors are some of the most lethal adult cancers and there is a concern that the incidence is increasing. It has been suggested that the reported increased incidence can be explained by improvements in diagnostic procedures, although this has not been totally resolved. The aim of our study was to describe the incidence trends of adult primary intracerebral tumors in four Nordic countries during a period with introduction of new diagnostic procedures and increasing prevalence of mobile phone users. Information about benign and malignant primary intracerebral tumor cases 20-79 years of age was obtained from the national cancer registries in Denmark, Finland, Norway and Sweden for the years 1969-98 and estimates of person-years at risk were calculated from the information obtained from national population registries. Annual age standardized incidence rates per 100,000 person-years were calculated and time trends analyses were carried out using Poisson regression. The overall incidence of all intracerebral tumors ranged from 8.4-11.8 for men and 5.8-9.3 for women, corresponding to an average annual increase of 0.6% for men (95% confidence interval [CI] = 0.4, 0.7) and 0.9% for women (95% CI = 0.7, 1.0). The increase in the incidence was confined to the late 1970s and early 1980s and coinciding with introduction of improved diagnostic methods. This increase was largely confined to the oldest age group. After 1983 and during the period with increasing prevalence of mobile phone users, the incidence has remained relatively stable for both men and women.     

Incidence of interstitial pneumonitis among breast cancer patients: a 10-year Danish population-based cohort study

Chemotherapy and radiation therapy may increase risk for interstitial pneumonitis (IP) in breast cancer patients, but there are little current population-based data on IP incidence in these patients. We assessed population-based incidence rates (IRs) of IP among Danish breast cancer patients and compared these with IRs for the Danish general population. Through the Danish Cancer Registry, we identified all Danish breast cancer patients (n=35 823) diagnosed between 1994 and 2004. Treatment data were obtained from the Danish Breast Cancer Cooperation Group database, and data on IP, from the Danish National Registry of Patients. We computed IRs of IP among breast cancer patients and age-standardised incidence rate ratios (SIRs) comparing breast cancer patients with the general population. During follow-up, 28 breast cancer patients were registered with an IP diagnosis (IR=17.3 per 100,000 person-years (p-y) (95% confidence intervals (95% CI): 11.7-24.6)). When follow-up was restricted to 1 year after the first breast cancer diagnosis, eight patients with IP were identified (IR=23.4 per 100,000 p-y (95% CI: 11.0-44.1)). The SIR comparing breast cancer patients with the general population was 8.4 (95% CI: 5.7-11.9). Thus, although IP is a rare adverse event among breast cancer patients, its risk is substantially higher than that in the general population.