Incidence Of Breast Cancer In Women Research Articles

Breast Cancer Risk After Bariatric Surgery and Influence of Insulin Levels

Obesity and insulin are risk factors for breast cancer, and retrospective studies suggest bariatric surgery reduces breast cancer risk in women. However, long-term prospective data on breast cancer risk after bariatric surgery and the role of baseline insulin levels are lacking. To examine if bariatric surgery is associated with breast cancer incidence in women and if treatment benefit is modified by baseline insulin levels. The Swedish Obese Subjects (SOS) study was a nonrandomized intervention trial designed to investigate the long-term effects of bariatric surgery on obesity-related mortality and morbidity. Study recruitment took place between 1987 and 2001, and median (IQR) follow-up time was 23.9 years (20.1-27.1) years. The study was conducted at 25 public surgical departments and 480 primary health care centers in Sweden and included 2867 women aged 37 to 60 years and with body mass index 38 or greater (calculated as weight in kilograms divided by height in meters squared). In the surgery group (n = 1420), 260 women underwent gastric banding, 970 vertical banded gastroplasty, and 190 gastric bypass. The remaining contemporaneously matched control individuals (n = 1447) received usual obesity care. Breast cancer, the main outcome of this secondary report, was not a predefined outcome in the SOS study. Breast cancer events were identified in the Swedish National Cancer Registry. The study population comprised 2867 women with a mean (SD) age of 48.0 (6.2) years. During follow-up, there were 154 breast cancer events, 66 in the surgery group and 88 in the usual care group, and a decreased risk of breast cancer was observed in the bariatric surgery group (hazard ratio [HR], 0.68; 95% CI, 0.49-0.94; P = .019; adjusted HR, 0.72; 95% CI, 0.52-1.01; P = .06). The surgical treatment benefit on breast cancer risk was greater in women with baseline insulin levels above the median 15.8 μIU/L (HR, 0.48; 95% CI, 0.31-0.74; P = .001; adjusted HR, 0.55; 95% CI, 0.35-0.86; P = .008) compared to those below (HR, 0.95; 95% CI, 0.59-1.53; P = .84; adjusted HR, 1.01; 95% CI, 0.61-1.66; P = .97; interaction P = .02). This prospective clinical trial indicated a reduced risk of breast cancer after bariatric surgery in women with obesity. The surgical treatment benefit was predominantly seen in women with hyperinsulinemia. ClinicalTrials.gov Identifier: NCT01479452.

Chemoprevention and Lifestyle Modifications for Risk Reduction in Sporadic and Hereditary Breast Cancer.

Female breast cancer is the most commonly diagnosed malignancy worldwide. Risk assessment helps to identify women at increased risk of breast cancer and allows the adoption of a comprehensive approach to reducing breast cancer incidence through personalized interventions, including lifestyle modification, chemoprevention, intensified surveillance with breast imaging, genetic counseling, and testing. Primary prevention means acting on modifiable risk factors to reduce breast cancer occurrence. Chemoprevention with tamoxifen, raloxifene, anastrozole, and exemestane has already shown benefits in decreasing breast cancer incidence in women at an increased risk for breast cancer. For healthy women carrying BRCA 1 or BRCA 2 pathogenic/likely pathogenic (P/LP) germline variants, the efficacy of chemoprevention is still controversial. Adopting chemoprevention strategies and the choice among agents should depend on the safety profile and risk-benefit ratio. Unfortunately, the uptake of these agents has been low. Lifestyle modifications can reduce breast cancer incidence, and the recommendations for BRCA 1 or BRCA 2 P/LP germline variant carriers are comparable to the general population. This review summarizes the most recent evidence regarding the efficacy of chemoprevention and lifestyle interventions in women with sporadic and hereditary breast cancer.

Estimated cardiorespiratory fitness in relation to overall, breast and prostate cancer incidence: the Norwegian HUNT study

To investigate the relationships between estimated cardiorespiratory fitness (eCRF) and the incidence of overall, breast, and prostate cancer in a large prospective cohort study. We included 46,968 cancer-free adults who participated in the second survey of the Trøndelag Health Study in Norway. Sex-specific non-exercise algorithms were used to estimate CRF. eCRF was classified into sex and age-specific tertiles, that is, into low, medium and high levels. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median of 22.1 years' follow-up, there were 7752 overall, 858 breast and 1376 prostate cancer cases. Medium and high levels of eCRF were associated with a reduced incidence of overall cancer in a dose-response manner in all participants (HR 0.96, 95% CI 0.90 to 1.01 and HR 0.85, 95% CI 0.79 to 0.91, respectively, and p-value for trend <0.001). No association was observed between eCRF and breast cancer incidence in women. Only the high level of eCRF seemed to be associated with a reduced incidence of prostate cancer in men (HR 0.85, 95% CI 0.72 to 1.02). eCRF may be a practical and cost-effective means of investigating the association between CRF and cancer incidence.

Breast Cancer Incidence in Relation to Long-Term Low-Level Exposure to Air Pollution in the ELAPSE Pooled Cohort.

Established risk factors for breast cancer include genetic disposition, reproductive factors, hormone therapy, and lifestyle-related factors such as alcohol consumption, physical inactivity, smoking, and obesity. More recently a role of environmental exposures, including air pollution, has also been suggested. The aim of this study, was to investigate the relationship between long-term air pollution exposure and breast cancer incidence. We conducted a pooled analysis among six European cohorts (n = 199,719) on the association between long-term residential levels of ambient nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone in the warm season (O3) and breast cancer incidence in women. The selected cohorts represented the lower range of air pollutant concentrations in Europe. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. During 3,592,885 person-years of follow-up, we observed a total of 9,659 incident breast cancer cases. The results of the fully adjusted linear analyses showed a HR (95% confidence interval) of 1.03 (1.00-1.06) per 10 μg/m³ NO2, 1.06 (1.01-1.11) per 5 μg/m³ PM2.5, 1.03 (0.99-1.06) per 0.5 10-5 m-1 BC, and 0.98 (0.94-1.01) per 10 μg/m³ O3. The effect estimates were most pronounced in the group of middle-aged women (50-54 years) and among never smokers. The results were in support of an association between especially PM2.5 and breast cancer. The findings of this study suggest a role of exposure to NO2, PM2.5, and BC in development of breast cancer.

133P Using breast cancer risk factors of women to estimate incidence of breast cancer in their sisters

A few breast cancer risk factors are well-established. Whether these existing risk factors and risk prediction tools can estimate breast cancer incidence for women’s sisters has not yet been investigated.

Vitamin D concentrations and breast cancer incidence among Black/African American and non-Black Hispanic/Latina women.

Vitamin D may protect against breast cancer. Although Black/African American women and Hispanic/Latina women have lower circulating vitamin D levels than non-Hispanic White women, few studies have examined the association between vitamin D and breast cancer within these racial/ethnic groups. The vitamin D-breast cancer association was evaluated using a case-cohort sample of self-identified Black/African American and non-Black Hispanic/Latina women participating in the US-wide Sister Study cohort. Circulating 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were measured using liquid chromatography-tandem mass spectrometry in blood samples collected at the baseline from 415 women (290 Black/African American women and 125 non-Black Hispanic/Latina women) who developed breast cancer. These were compared to concentrations in 1545 women (1084 Black/African American women and 461 Hispanic/Latina women) randomly selected from the cohort. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a mean follow-up of 9.2 years, women with circulating 25(OH)D concentrations above the clinical cut point for deficiency (20.0 ng/mL) had lower breast cancer rates than women with concentrations ≤ 20 ng/mL (HR, 0.79; 95% CI, 0.61-1.02). The inverse association was strongest among Hispanic/Latina women (HR, 0.52; 95% CI, 0.29-0.93), with a weaker association observed among Black/African American women (HR, 0.89; 95% CI, 0.68-1.18; P for heterogeneity = 0.13). There were no clear differences by menopausal status, follow-up time, estrogen receptor status, or invasiveness. Neither 24,25(OH)2 D nor the 24,25(OH)2 D to 25(OH)D ratio were independently associated with breast cancer risk. This prospective study supports the hypothesis that vitamin D may be protective against breast cancer incidence in women, including non-Black Hispanic/Latina and Black/African American women. Vitamin D may protect against breast cancer. Although women of color have lower average vitamin D levels than non-Hispanic White women, few studies have considered the role of race/ethnicity. In a sample of self-identified Black/African American and Hispanic/Latina women, we observed that vitamin D concentrations measured in blood were inversely associated with breast cancer, particularly among Latinas. These findings indicate that vitamin D may protect women against breast cancer, including those in racial/ethnic groups with low average circulating levels.

No association between breast pain and breast cancer: a prospective cohort study of 10 830 symptomatic women presenting to a breast cancer diagnostic clinic.

BackgroundWomen with breast pain constitute >20% of breast clinic attendees.AimTo investigate breast cancer incidence in women presenting with breast pain and establish the health economics of referring women with breast pain to secondary care.Design and settingA prospective cohort study of all consecutive women referred to a breast diagnostic clinic over 12 months.MethodWomen were categorised by presentation into four distinct clinical groups and cancer incidence investigated.ResultsOf 10 830 women, 1972 (18%) were referred with breast pain, 6708 (62%) with lumps, 480 (4%) with nipple symptoms, 1670 (15%) with ‘other’ symptoms. Mammography, performed in 1112 women with breast pain, identified cancer in eight (0.7%). Of the 1972 women with breast pain, breast cancer incidence was 0.4% compared with ∼5% in each of the three other clinical groups. Using ‘breast lump’ as reference, the odds ratio (OR) of women referred with breast pain having breast cancer was 0.05 (95% confidence interval = 0.02 to 0.09, P<0.001). Compared with reassurance in primary care, referral was more costly (net cost £262) without additional health benefits (net quality-adjusted life-year [QALY] loss −0.012). The greatest impact on the incremental cost-effectiveness ratio (ICER) was when QALY loss because of referral-associated anxiety was excluded. Primary care reassurance no longer dominated, but the ICER remained greater (£45 528/QALY) than typical UK National Health Service cost-effectiveness thresholds.ConclusionThis study shows that referring women with breast pain to a breast diagnostic clinic is an inefficient use of limited resources. Alternative management pathways could improve capacity and reduce financial burden.

Evaluating the prognostic performance of a polygenic risk score for breast cancer risk stratification

BackgroundPolygenic risk scores (PRS) could potentially improve breast cancer screening recommendations. Before a PRS can be considered for implementation, it needs rigorous evaluation, using performance measures that can inform about its future clinical value.ObjectivesTo evaluate the prognostic performance of a regression model with a previously developed, prevalence-based PRS and age as predictors for breast cancer incidence in women from the Estonian biobank (EstBB) cohort; to compare it to the performance of a model including age only.MethodsWe analyzed data on 30,312 women from the EstBB cohort. They entered the cohort between 2002 and 2011, were between 20 and 89 years, without a history of breast cancer, and with full 5-year follow-up by 2015. We examined PRS and other potential risk factors as possible predictors in Cox regression models for breast cancer incidence. With 10-fold cross-validation we estimated 3- and 5-year breast cancer incidence predicted by age alone and by PRS plus age, fitting models on 90% of the data. Calibration, discrimination, and reclassification were calculated on the left-out folds to express prognostic performance.ResultsA total of 101 (3.33‰) and 185 (6.1‰) incident breast cancers were observed within 3 and 5 years, respectively. For women in a defined screening age of 50–62 years, the ratio of observed vs PRS-age modelled 3-year incidence was 0.86 for women in the 75–85% PRS-group, 1.34 for the 85–95% PRS-group, and 1.41 for the top 5% PRS-group. For 5-year incidence, this was respectively 0.94, 1.15, and 1.08. Yet the number of breast cancer events was relatively low in each PRS-subgroup. For all women, the model’s AUC was 0.720 (95% CI: 0.675–0.765) for 3-year and 0.704 (95% CI: 0.670–0.737) for 5-year follow-up, respectively, just 0.022 and 0.023 higher than for the model with age alone. Using a 1% risk prediction threshold, the 3-year NRI for the PRS-age model was 0.09, and 0.05 for 5 years.ConclusionThe model including PRS had modest incremental performance over one based on age only. A larger, independent study is needed to assess whether and how the PRS can meaningfully contribute to age, for developing more efficient screening strategies.

Risk of Breast Cancer in Selected Women With Atypical Ductal Hyperplasia Who do not Undergo Surgical Excision.

To review breast cancer incidence in women with ADH diagnosed by CNB and managed nonoperatively. ADH found on CNB is associated with an upgrade to carcinoma in 10%-50% of women, thus surgical excision remains the standard of care. Safety of nonoperative management is unknown. ADH patients diagnosed between January 2004 and October 2018 were identified. Subsequent breast cancer events were compared between those who were excised and those who met predetermined criteria of low risk and were thus observed. Subsequent breast cancer events were classified as index site event if identified in the same quadrant as prior ADH. Multivariable logistic regression models were used to assess potential predictors of subsequent breast cancer events. Four hundred seventy-eight women with 483 ADH lesions were identified; 309 were observed and 174 underwent excision. Median follow-up was 5.2 years. Prior breast cancer history was the only factor associated with subsequent breast cancer risk (odds ratio 2.25, 95% confidence interval 1.04-4.87). After excluding patients with a breast cancer history, there was no association of age, race, chemoprevention, or surgical excision of ADH with future cancer risk. 21/387 patients without a breast cancer history developed a subsequent cancer; 10 (7.3%) in the surgical group and 11 (4.4%) in the observed ( P = 0.2). Two cancers were identified at the index site in the surgery group (2/137, 1.5%) and three in those observed (3/250, 1.2%). Observation, rather than surgical excision, is safe in select women with ADH. National guidelines should consider observation for this select group of patients.

Breast cancer mortality and overdiagnosis after implementation of population-based screening in Denmark

IntroductionService breast cancer screening is difficult to evaluate because there is no unscreened control group. Due to a natural experiment, where 20% of women were offered screening in two regions up to 17 years before other women, Denmark is in a unique position. We utilized this opportunity to assess outcome of service screening.Materials and methodsScreening was offered in Copenhagen from 1991 and Funen from 1993 to women aged 50–69 years. We used difference-in-differences methodology with a study group offered screening; a historical control group; a regional control group; and a regional–historical control group, comparing breast cancer mortality and incidence, including ductal carcinoma in situ, between study and historical control group adjusted for changes in other regions, and calculating ratios of rate ratios (RRR) with 95% confidence intervals (CI). Data came from Central Population Register; mammography screening databases; Cause of Death Register; and Danish Cancer Register.ResultsFor breast cancer mortality, the study group accumulated 1,551,465 person-years and 911 deaths. Long-term breast cancer mortality in Copenhagen was 20% below expected in absence of screening; RRR 0.80 (95% CI 0.71–0.90), and in Funen 22% below; RRR 0.78 (95% CI 0.68–0.89). Combined, cumulative breast cancer incidence in women followed 8+ years post-screening was 2.3% above expected in absence of screening; RRR 1.023 (95% CI 0.97–1.08).DiscussionBenefit-to-harm ratio of the two Danish screening programs was 2.6 saved breast cancer deaths per overdiagnosed case. Screening can affect only breast cancers diagnosed in screening age. Due to high breast cancer incidence after age 70, only one-third of breast cancer deaths after age 50 could potentially be affected by screening. Increasing upper age limit could be considered, but might affect benefit-to-harm ratio negatively.

Determinan Kejadian Kanker Payudara Pada Wanita Di Rsud Arifin Achmad Provinsi Riau Tahun 2019

Breast cancer is among the most discussed cancers because of its malignancy which often ends in death. Based on the 2013 Basic Health Research Data (Riskesdas), the number of breast cancer patients reached 61,682 cases in Indonesia. As in Riau Province according to the medical records of Arifin Achmad Regional Hospital, breast cancer ranks first with 325 cases out of 580 cases in Irna Surgical Cendrawasih in 2016. Purpose of this study was to determine the determinants of breast cancer incidence in women in Arifin Achmad Regional Hospital in Riau Province in 2019. This research uses a quantitative research design with a case control approach. The research instrument used was a questionnaire. The sampling technique was Consecutive Sampling. This research was conducted in May to July 2019. Case samples in this study were women who were diagnosed positive for breast cancer and control samples were women who were diagnosed with negative breast cancer. Univariate and bivariate data analysis with chi square test and multivariate analysis using Simple Logistic Regression test. The results showed the most dominant variables related to cause and effect with the incidence of breast cancer were a history of abortion 3.7 times, a history of hormonal contraceptive use 5.4 times, the age of first child birth&gt; 35 years 3 times, and the number of nulliparous children 2.3 times. It is expected that health workers and related institutions will be able to provide health education regarding the positive and negative impacts of contraceptive use, the importance of planning the marriage age and promoting family planning programs that have been launched by the government.

Knowledge of Potential Harms and Benefits of Tamoxifen among Women Considering Breast Cancer Preventive Therapy.

Tamoxifen reduces breast cancer incidence in women at increased risk, but may cause side effects. We examined women's knowledge of tamoxifen's potential harms and benefits, and the extent to which knowledge reflects subjective judgments of awareness and decision quality. After a hospital appointment, 408 (55.7%) women at increased risk of breast cancer completed a survey assessing objective knowledge about the potential benefit (risk reduction) and harms (endometrial cancer, thromboembolic events, and menopausal side effects) of tamoxifen, and subjective tamoxifen knowledge and decisional quality. Two hundred fifty-eight (63.2%) completed a 3-month follow-up survey. Sixteen percent (15.7%) of participants recognized the potential benefit and three major harms of using tamoxifen. These women were more likely to have degree-level education [vs. below degree level; OR, 2.24; 95% confidence interval (CI), 1.11-4.55] and good numeracy (vs. poor numeracy; OR, 5.91; 95% CI, 1.33-26.19). Tamoxifen uptake was higher in women who recognized all harms and benefits (vs. not recognizing; OR, 2.47; 95% CI, 0.94-6.54). Sixty-six percent (65.8%) of tamoxifen users were unaware of its potential benefit and harms. Most (87.1%) women reported feeling informed about tamoxifen, and subjective decisional quality was high [Mean (SD), 17.03 (1.87), out of 18]. Knowledge regarding the potential harms and benefit of tamoxifen is low in women considering prevention therapy, and they may need additional support to make informed decisions about tamoxifen preventive therapy.

MEDICAL AND STATISTICAL CHARACTERISTICS OF BREAST CANCER IN ST. PETERSBURG FEMALE RESIDENTS

Purpose.To analyze the main medical and statistical parameters, allowing to evaluate the results of breast cancer treatment.Patients and methods.Data on 4689 breast cancer (BC) patients were analyzed retrospectively. Inclusion criteria were: female, residence in St. Petersburg, diagnosis of BC established in 2011, 2012. The study also includes information on the options of BC surgical treatment, one-year mortality in breast cancer patients and index of the contingent accumulation in St. Petersburg in 2011–2017. For statistical data processing Statistica 12.0 for Windows, Population Cancer Register and MedInfo-4 were used. The differences in the groups of studies were considered statistically significant at p &lt; 0.05.Results.The prevalence of breast cancer among women in St. Petersburg varies from 532.6 per 100 000 population in 2011 to 545.00/0000 in 2012. In 2011 the incidence of BC in women in St. Petersburg was 46.210/0000 (standard deviation 1.05) and in 2012 – 49.50/0000 (standard deviation 1.05). The mean age of breast cancer patients is 64 years (standard deviation 12.25). Localization of a tumor in one of the glands was found in 4617 (98.5%) clinical observations. In 2,846 (60.7%) cases, the tumor sizes varied from 2 to 5 cm. Signs of infiltrative ductal carcinoma were histologically verified in 3689 (80%) cases. The proportion of single-stage breast reconstruction after mastectomy in the overall structure of surgeries in breast cancer patients increased in 2011–2017 more than 6.5 times. The 5-year survival rate in study groups was 64.4% and 63.3%.ConclusionsThe main statistical parameters of medical care (MC) analysis in breast cancer patients in St. Petersburg in 2011–2017 allow to state generally positive trends in the anticancer fight organization. The increase of the breast cancer incidence rates is partly due to the improved quality of examination and treatment of patients through the creation in the city of a system of high-tech MC, as well as to the particularly wary of doctors in detecting breast tumors.

PB2296 SURVEILLANCE BREAST SCREENING PROGRAMS FOR PATIENTS WHO UNDERWENT CHEST RADIATION THERAPY (LYMPHOMA SURVIVORS)

Background:Women who underwent chest radiation therapy (CRT) during pediatric/young‐adult age have an increased breast cancer (BC) risk. The cumulative BC incidence in women who underwent CRT is 13‐20%, higher than the incidence observed in the young female general population. BC is diagnosed on average about 15 years after CRT at about 40 years of age, compared with about 61 years in the non‐exposed female general population.Aims:From January 2018 to December 2018, a group of consecutive 46 patients (45 females, 1 male), aged between 23 and 62 (mean 44), who underwent CRT at least in the previous 8 years, underwent breast clinical, ultrasound (US) and mammographic examinations.Methods:Breast density at US was evaluated according to the BIRADS lexicon (homogeneous‐fat; homogeneous‐fibroglandular; heterogeneous) and compared with a control group of healthy patients (n = 46) with similar demographic features. Any statistical significant difference was searched by t‐student test for unpaired samples. The incidence of breast cancer in the examined series was assessed.Results:Among the examined series, 10/46 (22%) patients with homogeneous, 20/46 (43%) with fibroglandular and 16/46 (35%) with heterogeneous density were found. In the control group, 8/46 (17%) patients with homogeneous, 21/46 (46%) with fibroglandular and 17/46 (37%) with heterogeneous density were found. No significant difference occurred among the two groups of patients (p &gt; 0.05). 4/46 (3 females, 1 male) patients were affected by breast cancer (invasive ductal carcinoma, n = 3; ductal carcinoma in situ, n = 1) with a 9% incidence.Summary/Conclusion:A surveillance breast imaging protocol should be strongly recommended to patients with a previous CRT. Breast cancer incidence seems to be higher compared with general population. No significant effect on US breast density seems to exist in CRT patients. Future research should be directed at examining the underlying cancer biology and etiology of treatment induced cancers, as well as inherent and treatment‐induced genetic susceptibility of HL survivors.

Association of antidiabetic medication and statins with breast cancer incidence in women with type 2 diabetes

PurposeTo address the possible association between the use of metformin, other forms of antidiabetic medication (ADM) and statins with the incidence of breast cancer in women with type 2 diabetes (T2D).MethodsData were collected from a Finnish nationwide diabetes database (FinDM). The study cohort consisted of women diagnosed with T2D in 1996–2011 in Finland. In full-cohort analysis, Poisson regression was used to estimate hazard ratios (HRs) in relation to use of metformin, insulin, other forms of oral ADM and statins. In nested case–control analysis, up to 20 controls were matched for age and duration of diabetes to each case of breast cancer. Conditional logistic regression was used to estimate HRs in relation to medication use and cumulative use of different forms of ADM, and statins.Results2300 women were diagnosed with breast cancer during follow-up. No difference in breast cancer incidence was observed between metformin users [HR 1.02, 95% confidence interval (CI) 0.93–1.11] or statin users (HR 0.97, 95% CI 0.89–1.05) compared with non-users. In nested case–control analysis the results were similar. Use of insulin (HR 1.18, 95% CI 1.03–1.36) was associated with a slightly increased incidence of breast cancer.ConclusionsNo evidence of an association between the use of metformin or statins and the incidence of breast cancer in women with T2D was found. Among insulin users, a slightly higher incidence of breast cancer was observed.

The Risk of Breast Cancer in Women with Diabetes

Some observational studies have suggested an increased risk of breast cancer (BC) among diabetic patients. A meta-analysis was performed to assess the risk of BC in diabetic patients compared to nondiabetic patients. Studies were selected if they had a prospective design. Studies that compared BC incidence in women with diabetes to the incidence in the general population were excluded. Summary relative risks (SRR) were computed using a random-effect model. Eighteen studies were included in the meta-analysis, including 28,230,143 person-years of follow-up and 320,111 BC cases. A significantly increased risk of BC among diabetic patients compared to nondiabetic patients was found: SRR=1.13 (95% CI: 1.04, 1.24). There was a large amount of unexplained heterogeneity of results across studies (I²=95%), but no indication of publication bias. The SRR remained similar when the analysis was restricted to post-menopausal women (SRR=1.12 (95% CI: 0.99, 1.26)). Only two studies reported data in pre-menopausal women. In the 9 studies that adjusted for adiposity, both the SRR and the heterogeneity of results across studies substantially decreased (SRR=1.(95% CI: 0.97, 1.14), I²=21%). In contrast, in the 9 studies that did not adjust for adiposity, both the SRR and the heterogeneity increased (SRR=1.19 (95% CI: 1.01, 1.39), I²=98%). Only two studies included 1,723 and 14 BC cases among type 1 diabetic women. The RR for BC were 0.90 (95% CI: 0.85, 0.94) and RR=1.01 (95% CI: 0.60, 1.71), respectively. This analysis provides evidence for a moderately increased risk of BC in diabetic patients. The effect of the adjustment for BMI on the SRR and on the heterogeneity suggests that the increased BC risk appears to be linked to adiposity, and not to being diabetic. New studies should collect data allowing the assessment of Breast Cancer risk according to the duration of diabetes and treatments that favour weight loss. Disclosure M. Bota: None. P. Autier: Other Relationship; Self; Sanofi. P. Boyle: Other Relationship; Self; Sanofi.

Association of Schizophrenia With the Risk of Breast Cancer Incidence

Patients with schizophrenia are considered to have many risk factors for the development of cancer. However, the incidence of breast cancer in women with schizophrenia compared with the general population remains uncertain. To perform an updated meta-analysis to evaluate the association between schizophrenia and the risk of breast cancer. A systematic search of the PubMed and EMBASE databases was conducted using the search terms schizophrenia, schizophrenic, psychosis, combined with breast and cancer, tumor, neoplasm, or carcinoma. The final literature search was performed on August 15, 2017. Cohort studies reporting the standardized incidence ratio (SIR) for the risk of breast cancer in women with schizophrenia compared with the general population. The meta-analysis adhered to Meta-analysis of Observational Studies in Epidemiology and the Cochrane Handbook for Systematic Reviews of Interventions. Data extraction was performed independently. A random-effects model was used to pool the results, and a recently proposed prediction interval was calculated to describe the heterogeneity. The SIR for the risk of breast cancer in women with schizophrenia compared with the general population or those without schizophrenia. Twelve cohorts including 125 760 women were included in this meta-analysis. The results of the meta-analysis showed that schizophrenia was associated with a significantly increased risk of breast cancer incidence in women (SIR, 1.31; 95% CI, 1.14-1.50; P < .001), with significant heterogeneity (P < .001; I2 = 89%). Substantial between-study variance was also suggested by the wide prediction interval (0.81-2.10), which indicated that it is possible that a future study will show a decreased breast cancer risk in women with schizophrenia compared with the general population. The subgroup analysis results showed that the association was not significantly affected by whether breast cancer cases were excluded at baseline or the sample size of the included studies. The incidence of breast cancer in women with schizophrenia is higher than that of the general female population. However, significant heterogeneity exists among the included studies. Women with schizophrenia deserve intensive prevention and treatment of breast cancer.

Long-Term Use of Long-Acting Insulin Analogs and Breast Cancer Incidence in Women With Type 2 Diabetes.

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom's Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.

Abstract 4446: Molecular profiling and threshold expression of microRNAs in mammary tissue of asymptomatic women

Abstract Night shift-work and circadian dysfunction have been linked to increased incidence of breast cancer. Circadian modulation of gene expression is often mediated by microRNAs (miRNAs), small 18-25 nucleotide noncoding RNA molecules that regulate posttranscriptional gene expression via mRNA inactivation. Although miRNA dysregulation has been implicated in breast cancer development, the relationship between breast cancer incidence in women exposed to chronic circadian disruption and their miRNA profiles has not been examined due to the lack of existing normal profiles of expression. We first identified miRNA expressed in asymptomatic breast tissue and defined their baseline profiles in women exposed to a regular work schedule compared to those who experienced chronic circadian disruption by night shift work. Normal mammary tissue was obtained from women undergoing therapeutic breast reductions. Clinical metadata on work, stress, sleep, pregnancy, medical, medication, family, and surgical history were obtained through survey and chart review. We selected night shift work starting from 0700 to 0300 as a marker of circadian disruption. Our studies focused on two major comparisons. First, we determined qualitative oscillatory differences in miRNA variants expressed during day and night. Second, we determined statistically significant expression levels of those day and night miRNAs in shift workers. Mammary miRNA reads were mapped against the reference human genome and mature miRNA set. One-way ANOVA was used to compare miRNA expression levels between night shift and non-night shift workers, as well as miRNA expression between other clinical metadata. At present, twelve samples have undergone experimental and statistical analyses. Three out of the twelve samples were from night shift workers. One-way ANOVA was run on the top one hundred expressed miRNAs including hsa-miR-143-3p, hsa-miR-99a-5p, hsa-miR-21-5p, hsa-miR-10b-5p, and hsa-miR-148a-3p to exclude miRNAs with zero or extremely low counts. Analysis showed no significant difference in miRNA expression of normal samples between night shift and non-night-shift workers (p 0.06099), pregnant and nulliparous (p 0.2658), and women who breastfed and those who did not (p 0.111). There was significant difference in miRNA expression of normal samples between patients who had breast cancer in the opposite breast compared to those who did not (p 0.03269) and patients with sleep problems and those who did not (p 0.003448). It is interesting to note that night shift work and sleep problems both represent forms of circadian disruption, yet only the latter showed significant difference in miRNA expression between controls. It is expected that patients with cancer in the other breast may exhibit significantly different reads from patients who have never had breast cancer. Future analyses will be performed using additional samples to build on these findings. Citation Format: Andrew Y. Li, Kristin Knight, Margaret Kneifel, Mark Feldmann, Kurtis Moyer, Allan Dickerman, Carla Finkielstein. Molecular profiling and threshold expression of microRNAs in mammary tissue of asymptomatic women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4446. doi:10.1158/1538-7445.AM2017-4446

Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (<8,600 mg) and medium (8,600-88,900 mg) cumulative doses of aspirin did not reduce the risk of breast cancer. Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.