Use of beta-blockers and risk of contralateral breast cancer.

Beta-blockers have shown antineoplastic effects in laboratory studies but epidemiologic evidence in relation to contralateral breast cancer (CBC) is sparse. We investigated postdiagnosis beta-blocker use and risk of CBC in a cohort of 52 723 women with breast cancer by using nationwide Danish health registers and the Danish Breast Cancer Group database. We defined postdiagnosis beta-blocker use as a time-varying covariate starting 1 year after a second prescription was redeemed. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with beta-blocker use compared to nonuse. We identified 1444 women with CBC of whom 209 women were beta-blocker users. We found an overall HR of 1.08 (95% CI: 0.93-1.27) for beta-blocker use and risk of CBC with no substantial variation according to cumulative amount, intensity or selectivity of beta-blocker use. Hence, our cohort study of women with breast cancer did not sustain a protective effect of beta-blocker use on risk of CBC, irrespective of beta-blocker type.

The role of H1 antihistamines in contralateral breast cancer: a Danish nationwide cohort study.

BACKGROUND: Preclinical studies have shown both pro- and antineoplastic effects of antihistamines. Here, we evaluated the effect of H1 antihistamines on contralateral breast cancer (CBC) risk, and whether cationic amphiphilic (CAD) antihistamines could increase the sensitivity to chemotherapy. METHODS: From the Danish Breast Cancer Group clinical database, we identified all women aged ≥20 years with a first-time diagnosis of breast cancer during 1996-2012. Information on drug use, CBC and potential confounding factors was retrieved from nationwide registries. Using Cox proportional hazard regression models, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with H1-antihistamine use. RESULTS: We identified 52,723 patients with breast cancer with a total of 310,583 person-years of follow-up. Among them, 1444 patients developed a new primary tumour in the contralateral breast. Post-diagnosis use of H1 antihistamines (≥2 prescriptions) was not strongly associated with CBC risk (HR 1.08, 95% CI: 0.90-1.31) compared with non-use (<2 prescriptions). Use of CAD antihistamines among patients receiving chemotherapy was not associated with a decrease in CBC risk. CONCLUSIONS: Taken together, our findings do not suggest any association of H1-antihistamine use with CBC development.

Ovarian removal at or after benign hysterectomy and breast cancer: a nationwide cohort study.

PURPOSE: Large-scale population-based registry studies investigating the risk of breast cancer after removal of both ovaries at hysterectomy for benign conditions in women with no known genetic predisposition to cancer are needed. We aimed to perform such a study taking into account the age at surgery status and use of hormone replacement therapy (HRT). METHODS: Within the female population of Denmark born 1937-1996, we evaluated breast cancer incidence after unilateral or bilateral oophorectomy concomitant with or after benign hysterectomy in comparison with no surgery and with hysterectomy alone using health registry data during 1978-2016. In a subpopulation followed from 1996, the analyses were stratified according to use of HRT. RESULTS: We found a reduced risk of breast cancer among women aged < 45 years at bilateral oophorectomy compared with women with hysterectomy alone (HR = 0.78; 95% CI 0.66, 0.92), whereas slightly increased risks were seen in women above 50 years. In the subpopulation, non-users of HRT aged ≥ 50 years at oophorectomy had a HR of 0.74 (95% CI 0.56, 0.98) for breast cancer after bilateral oophorectomy compared with hysterectomy alone. CONCLUSIONS: Our large-scale study covering four decades provides evidence that bilateral oophorectomy performed at young age in women with benign indications for hysterectomy is associated with a reduction in breast cancer risk. The finding of a negative association at older ages in women not using HRT deserves further attention.

Nonaspirin NSAIDs and contralateral breast cancer risk.

Laboratory studies suggest that inhibition of the cyclooxygenase (COX)-2 enzymes inhibits breast cancer development. We aimed to evaluate whether postdiagnosis use of COX-2 selective or other nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of contralateral breast cancer (CBC) among Danish breast cancer patients. From the clinical database of the Danish Breast Cancer Group, we identified 52,723 women diagnosed with breast cancer between 1996 and 2012. Data on nonaspirin NSAID use, CBC and potential confounding variables were obtained from nationwide registries. We defined postdiagnosis use (two or more prescriptions) as a time-varying covariate with a one-year lag. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with nonaspirin NSAID use. During a median follow-up of 4.8 years (interquartile range: 2.3-9 years), 1,444 patients were diagnosed with CBC. Overall, postdiagnosis use of nonaspirin NSAID was associated with an adjusted HR for CBC of 0.98 (95% CI: 0.87-1.11). The HRs did not vary substantially with duration or intensity of nonaspirin NSAID use. Moreover, similar associations were found for COX-2 selective (HR: 1.02; 95% CI: 0.85-1.23) and nonselective (HR: 0.96; 95% CI: 0.82-1.13) nonaspirin NSAIDs. In conclusion, our nationwide cohort study of breast cancer patients does not suggest a reduced risk of CBC with nonaspirin NSAID use regardless of the COX-2 selectivity.

Preventive drug therapy and contralateral breast cancer: summary of the evidence of clinical trials and observational studies.

Background: Breast cancer patients have a lifelong 2-4-fold increased risk of developing a second primary tumor in the contralateral breast compared with the risk for a first primary breast cancer in the general female population. Prevention of contralateral breast cancer (CBC) has received increased attention during recent decades. Here, we summarize and discuss the available literature on drug preventive therapy and CBC.Results: The endocrine-targetting drugs, tamoxifen and aromatase inhibitors are used as standard adjuvant treatment for estrogen receptor (ER)-positive breast cancer. Both are associated with relative risk reductions of CBC of up to 50%, but incur serious side effects. Several prescription drugs originally developed for other purposes, including bisphosphonates, statins, non-steroidal anti-inflammatory drugs, metformin, anti-hypertensives and retinoids, have shown anti-cancer activity in preclinical models. However, results of observational studies on CBC are sparse and inconsistent, with only statins demonstrating promise as preventive agents and a potential treatment option for ER-negative breast cancer patients.Conclusion: Future studies are needed to assess the effect of statins in risk reduction and to identify other drugs with chemopreventive potential against CBC. Eventually, efforts must be directed towards identifying those breast cancer patients likely to benefit most from specific preventive therapies.

Worse survival after breast cancer in women with anorexia nervosa.

PURPOSE: A history of anorexia nervosa has been associated with a reduced risk of developing breast cancer. We investigated survival after breast cancer among women with a prior anorexia nervosa diagnosis compared with women in a population comparison group. METHODS: This register-based study included combined data from Sweden, Denmark and Finland. A total of 76 and 1462 breast cancer cases identified among 22,654 women with anorexia nervosa and 224,619 women in a population comparison group, respectively, were included in the study. Hazard ratios (HR) for overall and breast cancer-specific mortality after breast cancer diagnosis were estimated using Cox regression. Cause of death was available only for Swedish and Danish women; therefore, the analysis on breast cancer-specific mortality was restricted to these women. RESULTS: We observed 23 deaths after breast cancer among anorexia nervosa patients and 247 among population comparisons. The overall mortality after the breast cancer diagnosis was increased in women with a history of anorexia nervosa compared with population comparisons (HR 2.5, 95% CI 1.6-3.9) after adjustment for age, period and extent of disease. Results were similar for overall (HR 2.3, 95% CI 1.4-3.6) and breast cancer-specific mortality (HR 2.1, 95% CI 1.3-3.6) among Swedish and Danish women. CONCLUSIONS: We found that female breast cancer patients with a prior diagnosis of anorexia nervosa have a worse survival compared with other breast cancer patients.

Low-dose aspirin use and risk of contralateral breast cancer: a Danish nationwide cohort study.

Observational studies of aspirin use and breast cancer risk have provided inconsistent results. The occurrence of contralateral breast cancer (CBC) among breast cancer survivors may serve as a useful high-risk model to identify preventive drug effects. Using this model, we examined the association between post-diagnosis use of low-dose aspirin and risk of CBC. We identified all women recorded with a first primary breast cancer in the Danish Breast Cancer Cooperative Group Database between 1996 and 2012. Information on drug use, tumor and patient characteristics, treatment, and CBC was obtained from nationwide registries. In the main analysis, we defined time-varying post-diagnosis low-dose aspirin use as two or more prescriptions filled during follow-up and applied a one-year exposure lag. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnosis low-dose aspirin use and CBC risk. Among 52,723 breast cancer patients, 1,444 women developed CBC during a median follow-up of 4.8 years. The adjusted HR for CBC associated with post-diagnosis use of low-dose aspirin was 0.91 (95% CI: 0.75-1.09). We observed no substantial variation in HRs according to pattern of low-dose aspirin use or estrogen receptor status of the first or the contralateral breast cancer. In conclusion, this large nationwide cohort study of breast cancer survivors does not provide strong evidence suggesting an association between post-diagnosis use of low-dose aspirin and risk of CBC.