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Background A paucity of research addresses breast cancer screening strategies for women at lower-than-average breast cancer risk. The aim of this study was to examine screening harms and benefits among women aged 50-74 years at lower-than-average breast cancer risk by breast density. Methods Three well-established, validated Cancer Intervention and Surveillance Network models were used to estimate the lifetime benefits and harms of different screening scenarios, varying by screening interval (biennial, triennial). Breast cancer deaths averted, life-years and quality-adjusted life-years gained, false-positives, benign biopsies, and overdiagnosis were assessed by relative risk (RR) level (0.6, 0.7, 0.85, 1 [average risk]) and breast density category, for US women born in 1970. Results Screening benefits decreased proportionally with decreasing risk and with lower breast density. False-positives, unnecessary biopsies, and the percentage overdiagnosis also varied substantially by breast density category; false-positives and unnecessary biopsies were highest in the heterogeneously dense category. For women with fatty or scattered fibroglandular breast density and a relative risk of no more than 0.85, the additional deaths averted and life-years gained were small with biennial vs triennial screening. For these groups, undergoing 4 additional screens (screening biennially [13 screens] vs triennially [9 screens]) averted no more than 1 additional breast cancer death and gained no more than 16 life-years and no more than 10 quality-adjusted life-years per 1000 women but resulted in up to 232 more false-positives per 1000 women. Conclusion Triennial screening from age 50 to 74 years may be a reasonable screening strategy for women with lower-than-average breast cancer risk and fatty or scattered fibroglandular breast density.

Background Surveillance with annual mammography and breast magnetic resonance imaging (MRI) is recommended for female survivors of childhood cancer treated with chest radiation, yet benefits, harms, and costs are uncertain. Objective To compare the benefits, harms, and cost-effectiveness of breast cancer screening strategies in childhood cancer survivors. Design Collaborative simulation modeling using 2 Cancer Intervention and Surveillance Modeling Network breast cancer models. Data sources Childhood Cancer Survivor Study and published data. Target population Women aged 20 years with a history of chest radiotherapy. Time horizon Lifetime. Perspective Payer. Intervention Annual MRI with or without mammography, starting at age 25, 30, or 35 years. Outcome measures Breast cancer deaths averted, false-positive screening results, benign biopsy results, and incremental cost-effectiveness ratios (ICERs). Results of base-case analysis Lifetime breast cancer mortality risk without screening was 10% to 11% across models. Compared with no screening, starting at age 25 years, annual mammography with MRI averted the most deaths (56% to 71%) and annual MRI (without mammography) averted 56% to 62%. Both strategies had the most screening tests, false-positive screening results, and benign biopsy results. For an ICER threshold of less than $100 000 per quality-adjusted life-year gained, screening beginning at age 30 years was preferred. Results of sensitivity analysis Assuming lower screening performance, the benefit of adding mammography to MRI increased in both models, although the conclusions about preferred starting age remained unchanged. Limitation Elevated breast cancer risk was based on survivors diagnosed with childhood cancer between 1970 and 1986. Conclusion Early initiation (at ages 25 to 30 years) of annual breast cancer screening with MRI, with or without mammography, might reduce breast cancer mortality by half or more in survivors of childhood cancer. Primary funding source American Cancer Society and National Institutes of Health.

Background Early initiation of breast cancer screening is recommended for high-risk women, including survivors of childhood cancer treated with chest radiation. Recent studies suggest that female survivors of childhood leukemia or sarcoma treated without chest radiation are also at elevated early onset breast cancer risk. However, the potential clinical benefits and cost-effectiveness of early breast cancer screening among these women are uncertain. Methods Using data from the Childhood Cancer Survivor Study, we adapted 2 Cancer Intervention and Surveillance Modeling Network simulation models to reflect the elevated risks of breast cancer and competing mortality among leukemia and sarcoma survivors. Costs and utility weights were based on published studies and databases. Outcomes included breast cancer deaths averted, false-positive screening results, benign biopsies, and incremental cost-effectiveness ratios. Results In the absence of screening, the lifetime risk of dying from breast cancer among survivors was 6.8% to 7.0% across models. Early initiation of annual mammography with breast magnetic resonance imaging screening between ages 25 and 40 years would avert 52.6% to 64.3% of breast cancer deaths. When costs and quality-of-life impacts were considered, screening starting at age 40 years was the only strategy with an incremental cost-effectiveness ratio below the $100 000 per quality-adjusted life-year (QALY) gained cost-effectiveness threshold ($27 680 to $44 380 per QALY gained across models). Conclusions Among survivors of childhood leukemia or sarcoma, early initiation of breast cancer screening at age 40 years may reduce breast cancer deaths by half and is cost-effective. These findings could help inform screening guidelines for survivors treated without chest radiation.

Background Digital breast tomosynthesis (DBT) is increasingly being used for routine breast cancer screening. We projected the long-term impact and cost-effectiveness of DBT compared to conventional digital mammography (DM) for breast cancer screening in the United States. Methods Three Cancer Intervention and Surveillance Modeling Network breast cancer models simulated US women ages 40 years and older undergoing breast cancer screening with either DBT or DM starting in 2011 and continuing for the lifetime of the cohort. Screening performance estimates were based on observational data; in an alternative scenario, we assumed 4% higher sensitivity for DBT. Analyses used federal payer perspective; costs and utilities were discounted at 3% annually. Outcomes included breast cancer deaths, quality-adjusted life-years (QALYs), false-positive examinations, costs, and incremental cost-effectiveness ratios (ICERs). Results Compared to DM, DBT screening resulted in a slight reduction in breast cancer deaths (range across models 0–0.21 per 1000 women), small increase in QALYs (1.97–3.27 per 1000 women), and a 24–28% reduction in false-positive exams (237–268 per 1000 women) relative to DM. ICERs ranged from $195 026 to $270 135 per QALY for DBT relative to DM. When assuming 4% higher DBT sensitivity, ICERs decreased to $130 533–$156 624 per QALY. ICERs were sensitive to DBT costs, decreasing to $78 731 to $168 883 and $52 918 to $118 048 when the additional cost of DBT was reduced to $36 and $26 (from baseline of $56), respectively. Conclusion DBT reduces false-positive exams while achieving similar or slightly improved health benefits. At current reimbursement rates, the additional costs of DBT screening are likely high relative to the benefits gained; however, DBT could be cost-effective at lower screening costs.

Controversy remains regarding the optimal margin width for patients with ductal carcinoma in situ (DCIS) who undergo breast conserving surgery (BCS). Women with a primary DCIS diagnosis were enrolled in a statewide population-based cohort from 1997 to 2006. Patients were surveyed every two years with follow-up data available through 2016. Surgical pathology reports were collected for 559 participants following breast conserving surgery. Multivariable Cox proportional hazard models evaluated relationships between locoregional recurrence (LRR) and margin width in the presence or absence of adjuvant radiation therapy while controlling for age, menopausal status and duration of endocrine therapy use. The majority of women in this study were over 50yo (74%), 34% had high grade disease, and 77% underwent radiation. The overall LRR rate was 12%. A LRR occurred in 46 women who had radiation (11%) and 23 women who did not undergo radiation (19%). Univariate analysis identified smaller margin width, younger age, premenopausal status, no radiotherapy, and shorter endocrine therapy use associated with LRR. Multivariable models demonstrated that close margins (

Objective To identify the most common causes of death and potentially modifiable risk factors in endometrial cancer patients. Methods 745 women diagnosed with incident endometrial cancer were enrolled in a population-based study from 1991 to 1994. Participants completed structured interviews about 1 year after diagnosis. Study files were linked with the National Death Index to identify dates and causes of death through 2016. Proportional hazards regression was used to estimate hazard rate ratios for cause of death adjusting for age and stage of disease. Hazard ratios were also examined according to comorbidities. Results Of the 745 women, 450 were deceased after a median of 19.9 years. The two most common causes of death were cardiovascular disease (N = 145, 32%) and any cancer (N = 135, 30%), with only 10% of women dying from endometrial cancer (N = 46). Obesity, diabetes and smoking increased risk of all-cause mortality (HRR 1.77, 95%CI 1.36–2.31; HRR 1.74, 95%CI 1.34–2.27; HRR 1.59, 95%CI 1.16–2.17). Diabetes also increased risk of cardiovascular disease-specific mortality (HRR 1.98, 95%CI 1.38–3.08), but not endometrial cancer mortality (HRR 0.55, 95%CI 0.21–1.48). Neither obesity nor smoking was associated with increased risk of cardiovascular disease-specific mortality (HRR 1.46, 95%CI 0.92–2.32; HRR 1.21, 95%CI 0.67–2.18) nor endometrial-cancer specific mortality (HRR 1.81, 95%CI 0.83–3.93; HRR 0.61, 95%CI 0.17–2.15). Conclusions Endometrial cancer patients were 3 times more likely to die of cardiovascular disease than endometrial cancer. Obesity, smoking and diabetes increase the risk of death in these patients and are potentially modifiable. Clinical trials should be developed that incorporate counseling regarding these risk factors into survivorship care to determine impact on mortality.

PURPOSE: Higher mortality after a breast cancer diagnosis has been observed among women who are obese. We investigated the relationships between body mass index (BMI) and all-cause or breast cancer-specific mortality after a diagnosis of locoregional breast cancer. METHODS: Women diagnosed in 2004 with AJCC Stage I, II, or III breast cancer (n = 5394) were identified from a population-based National Program of Cancer Registries (NPCR) patterns of care study (POC-BP) drawing from registries in seven U.S. states. Differences in overall and breast cancer-specific mortality were investigated using Cox proportional hazards regression models adjusting for demographic and clinical covariates, including age- and stage-based subgroup analyses. RESULTS: In women 70 or older, higher BMI was associated with lower overall mortality (HR for a 5 kg/m(2) difference in BMI = 0.85, 95% CI 0.75–0.95). There was no significant association between BMI and overall mortality for women under 70. BMI was not associated with breast cancer death in the full sample, but among women with Stage I disease; those in the highest BMI category had significantly higher breast cancer mortality (HR for BMI ≥ 35 kg/m(2) vs. 18.5–24.9 kg/m(2) = 4.74, 95% CI 1.78–12.59). CONCLUSIONS: Contrary to our hypothesis, greater BMI was not associated with higher overall mortality. Among older women, BMI was inversely related to overall mortality, with a null association among younger women. Higher BMI was associated with breast cancer mortality among women with Stage I disease, but not among women with more advanced disease.

BACKGROUND: Health literacy is the ability to perform basic reading and numerical tasks to function in the health care environment. The purpose of this study is to describe how health literacy is related to perceived coordination of care reported by breast cancer patients. METHODS: Data were retrieved from the PCORI-sponsored “Share Thoughts on Breast Cancer” Study including demographic factors, perceived care coordination and responsiveness of care, and self-reported health literacy obtained from a mailed survey completed by 62% of eligible breast cancer survivors (N=1,221). Multivariable analysis of variance was used to characterize the association between presence of a single health care professional that coordinated care (“care coordinator”) and perceived care coordination, stratified by health literacy level. RESULTS: Health literacy was classified as low in 24% of patients, medium in 34%, and high in 42%. Women with high health literacy scores were more likely to report non-Hispanic white race/ethnicity, private insurance, higher education and income, and fewer comorbidities (all p

Objective. Breast cancer simulation models must take changing mortality rates into account to evaluate the potential impact of cancer control interventions. We estimated mortality rates due to breast cancer and all other causes combined to determine their impact on overall mortality by year, age, and birth cohort. Methods. Based on mortality rates from publicly available datasets, an age-period-cohort model was used to estimate the proportion of deaths due to breast cancer for US women aged 0 to 119 years, with birth years 1900 to 2000. Breast cancer mortality was calculated as all-cause mortality multiplied by the proportion of deaths due to breast cancer; other-cause mortality was the difference between all-cause and breast cancer mortality. Results. Breast cancer and other-cause mortality rates were higher for older ages and birth cohorts. The percent of deaths due to breast cancer increased across birth cohorts from 1900 to 1940 then decreased. Among 50-year-old women, in the 1920 birth cohort, 52 (9.9%) of 100,000 deaths (95% CI, 9.8% to 10.1%) were attributed to breast cancer whereas 476 of 100,000 were due to other causes; in the 1960 birth cohort, 22 (8.5%) of 100,000 deaths (95% CI, 8.3% to 8.7%) were attributed to breast cancer with 242 of 100,000 deaths due to other causes. The percentage of all deaths due to breast cancer was highest (4.1% to 12.9%) for women in their 40s and 50s for all birth cohorts. Conclusions. This study offers evidence that advances in breast cancer screening and treatment have reduced breast cancer mortality for women across the age spectrum, and provides estimates of age-, year- and birth cohort-specific competing mortality rates for simulation models. Other-cause mortality estimates are important in these models because most women die from causes other than breast cancer.

The University of Wisconsin Breast Cancer Epidemiology Simulation Model (UWBCS), also referred to as Model W, is a discrete-event microsimulation model that uses a systems engineering approach to replicate breast cancer epidemiology in the US over time. This population-based model simulates the lifetimes of individual women through 4 main model components: breast cancer natural history, detection, treatment, and mortality. A key feature of the UWBCS is that, in addition to specifying a population distribution in tumor growth rates, the model allows for heterogeneity in tumor behavior, with some tumors having limited malignant potential (i.e., would never become fatal in a woman’s lifetime if left untreated) and some tumors being very aggressive based on metastatic spread early in their onset. The model is calibrated to Surveillance, Epidemiology, and End Results (SEER) breast cancer incidence and mortality data from 1975 to 2010, and cross-validated against data from the Wisconsin cancer reporting system. The UWBCS model generates detailed outputs including underlying disease states and observed clinical outcomes by age and calendar year, as well as costs, resource usage, and quality of life associated with screening and treatment. The UWBCS has been recently updated to account for differences in breast cancer detection, treatment, and survival by molecular subtypes (defined by ER/HER2 status), to reflect the recent advances in screening and treatment, and to consider a range of breast cancer risk factors, including breast density, race, body-mass-index, and the use of postmenopausal hormone therapy. Therefore, the model can evaluate novel screening strategies, such as risk-based screening, and can assess breast cancer outcomes by breast cancer molecular subtype. In this article, we describe the most up-to-date version of the UWBCS.

Background: Increase in breast cancer incidence associated with mammography screening diffusion may have attenuated risk associations between family history and breast cancer. Methods: The proportions of women ages 40 to 74 years reporting a first-degree family history of breast cancer were estimated in the Breast Cancer Surveillance Consortium cohort (BCSC: N = 1,170,900; 1996–2012) and the Collaborative Breast Cancer Study (CBCS: cases N = 23,400; controls N = 26,460; 1987–2007). Breast cancer (ductal carcinoma in situ and invasive) relative risk estimates and 95% confidence intervals (CI) associated with family history were calculated using multivariable Cox proportional hazard and logistic regression models. Results: The proportion of women reporting a first-degree family history increased from 11% in the 1980s to 16% in 2010 to 2013. Family history was associated with a >60% increased risk of breast cancer in the BCSC (HR, 1.61; 95% CI, 1.55–1.66) and CBCS (OR, 1.64; 95% CI, 1.57–1.72). Relative risks decreased slightly with age. Consistent trends in relative risks were not observed over time or across stage of disease at diagnosis in both studies, except among older women (ages 60–74) where estimates were attenuated from about 1.7 to 1.3 over the last 20 years (P trend = 0.08 for both studies). Conclusions: Although the proportion of women with a first-degree family history of breast cancer increased over time and by age, breast cancer risk associations with family history were nonetheless fairly constant over time for women under age 60. Impact: First-degree family history of breast cancer remains an important breast cancer risk factor, especially for younger women, despite its increasing prevalence in the mammography screening era. Cancer Epidemiol Biomarkers Prev; 26(12); 1753–60. ©2017 AACR.

Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

10500 Background: Inherited pathogenic variants in ATM, CHEK2, and PALB2 confer moderate to high risks of breast cancer. The optimal approach to screening in these women has not been established. Methods: We used two simulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) and data from the Cancer Risk Estimates Related to Susceptibility consortium (CARRIERS) to project lifetime breast cancer incidence and mortality in ATM, CHEK2, and PALB2 carriers. We simulated screening with annual mammography from ages 40-74 alone and with annual magnetic resonance imaging (MRI) starting at ages 40, 35, 30, and 25. Joint and separate mammography and MRI screening performance was based on published literature. Lifetime outcomes per 1,000 women were reported as means and ranges across both models. Results: Estimated risk of breast cancer by age 80 was 22% (21-23%) for ATM, 28% (26-30%) for CHEK2, and 40% (38-42%) for PALB2. Screening with MRI and mammography reduced breast cancer mortality by 52-60% across variants (Table). Compared to no screening, starting MRI at age 30 increased life years (LY)/1000 women by 501 (478-523) in ATM, 620 (587-652) in CHEK2, and 1,025 (998-1,051) in PALB2. Starting MRI at age 25 versus 30 gained 9-12 LY/1000 women with 517-518 additional false positive screens and 197-198 benign biopsies. Conclusions: For women with ATM, CHEK2, and PALB2 pathogenic variants, breast cancer screening with MRI and mammography halves breast cancer mortality. These mortality benefits are similar to those for MRI screening for BRCA1/2 mutation carriers and should inform practice guidelines.[Table: see text]

e18524 Background: Treatment and survival disparities faced by Medicaid patients are documented for pancreatic, colon-rectosigmoid, and liver cancers at a national level. Studies show these disparities persist at academic medical centers. We assessed Medicaid treatment and survival outcomes among University of Wisconsin-Health (UWH) pancreatic, colon-rectosigmoid, and liver cancer patients to determine whether national trends persisted at this academic medical center. Methods: We included UWH registry data for 1567 pancreatic, 2313 colon-rectosigmoid, and 1027 liver cancer patients ages 18+ from 2004-2016. We performed multivariable logistic regression to estimate odds ratios (ORs) to assess insurance disparities in intended resection and Cox Proportional regression to estimate hazard ratios (HRs) to assess all-cause mortality disparities for each cancer, adjusting for age, sex, race/ethnicity, BMI, comorbidity, stage, rurality, and insurance. Results: Median overall survival was 6.5 months (range 0.1-147.5) for pancreatic, 12.8 months (0.1-167.5) for colon-rectosigmoid, and 12.5 months (0.1-168.7) for liver cancer patients. 3% of pancreatic, 5% of colon-rectosigmoid, and 9% of liver cancer patients had Medicaid Insurance. Medicaid patients were less likely to be older and non-Hispanic White than private insurance (private) patients for each cancer. Medicaid patients were diagnosed with more distant disease for colon-rectosigmoid and liver cancers and less distant disease for pancreatic cancer. Medicaid patients were less likely to receive surgery vs private patients for pancreatic (OR 0.41, 95% CI 0.16-1.08) and liver (OR 0.62, 0.26-1.49) cancers, though confidence intervals were wide. Insurance was not associated with surgery in colon-rectosigmoid cancer patients (OR 0.97, 0.48-1.97). Medicaid patients had a higher risk of death vs private patients for colon rectosigmoid cancer (HR 1.50, 1.12-2.01). Risk of death was modestly elevated for Medicaid vs private patients for pancreatic (HR 1.35, 0.97-1.87) but not liver (HR 1.07, 0.77-1.48) cancer. Conclusions: Medicaid pancreatic and liver cancer patients may be less likely to receive surgery than private patients in our one center study. Results suggested that Medicaid pancreatic and colon-rectosigmoid cancer patients may have a slightly elevated risk of death vs private patients, though this needs confirmation in larger samples. Future studies should explore at which local, state, and regional levels Medicaid pancreatic, colon-rectosigmoid, and liver cancer patients experience treatment and survival disparities vs private insurance patients. These studies, combined with Medicaid expansion studies, can guide healthcare leaders and policy makers to design context-appropriate interventions to reduce insurance-related disparities in cancer treatment and outcomes.

Inflammatory breast cancer (IBC) is a rare yet aggressive form of breast cancer. We examined differences in patient demographics and outcomes in IBC compared to locally advanced breast cancer (LABC) and all other breast cancer patients from the Breast and Prostate Cancer Data Quality and Patterns of Care Study (POC-BP), containing information from cancer registries in seven states. Out of 7,624 cases of invasive carcinoma, IBC and LABC accounted for 2.2% (N=170) and 4.9% (N=375), respectively. IBC patients were more likely to have a higher number (P=0.03) and severity (P=0.01) of comorbidities than other breast cancer patients. Among IBC patients, a higher percentage of patients with metastatic disease versus nonmetastatic disease were black, on Medicaid, and from areas of higher poverty and more urban areas. Black and Hispanic IBC patients had worse overall and breast cancer-specific survival than white patients; moreover, IBC patients with Medicaid, patients from urban areas, and patients from areas of higher poverty and lower education had worse outcomes. These data highlight the effects of disparities in race and socioeconomic status on the incidence of IBC as well as IBC outcomes. Further work is needed to reveal the causes behind these disparities and methods to improve IBC outcomes.

Background The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors. Methods Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression. Results DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups. Conclusions Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society.

Background: Socioeconomic-based treatment disparities are well-documented in pancreatic cancer in the United States. Studies have found treatment disparities by race and ethnicity, insurance, income, sex, and age. We examined 14 years of pancreatic cancer intended first course treatment data in a Midwestern state to identify state-specific disparities. Methods: Data from 8,416 pancreatic cancer patients aged over 18 diagnosed with adenocarcinoma, NOS or infiltrating duct carcinoma, NOS from 2004 to 2017 were obtained from the Wisconsin Cancer Reporting System. Adjusted logistic regression was performed to describe the association between patient characteristics and intended first course treatment. Treatment was defined as radiation, chemotherapy, or surgery, alone or in combination. The analysis was completed for all patients. It was repeated for the subset of 5,005 Medicare Patients to examine disparities by Medicare subtype. Race/ethnicity, sex, rurality, and insurance were factors of interest. Age and stage at diagnosis were included as confounders. Results: The mean overall survival of the 8,416 patients was 9.9 months. 70.5% of patients received treatment. 53% of patients were diagnosed with metastatic disease. The adjusted odds ratio of receiving treatment was 0.52 (0.41-0.65) for Non-Hispanic Black patients, 0.46 (0.24- 0.88) for Non-Hispanic Asian patients, and 0.46 (0.22-0.94) for patients categorized as ‘Other’ race/ethnicity compared to Non-Hispanic White patients. The adjusted odds ratio of receiving treatment was 0.90 (0.81-1.00) for female compared to male patients. The adjusted odds ratio of receiving treatment was 0.40 (0.29-0.54) for Medicaid patients, 0.80 (0.66-0.97) for Medicare patients, 0.44 (0.32-0.61) for Military patients, 0.18 (0.09-0.35) for Not Insured patients, and 0.24 (0.15-0.39) for Self Pay patients compared to Private Insurance patients. Among the 5,005 Medicare patients, the adjusted odds ratio of receiving treatment was 0.49 (0.35-0.68) for Non-Hispanic Black compared to Non-Hispanic White patients, 0.86 (0.76-0.98) for female compared to male patients, and 0.45 (0.33-0.62) for Medicare with Medicaid eligibility compared to Medicare, NOS patients. The adjusted odds ratio of receiving treatment was 1.42 (1.19-1.69) for Medicare patients with a supplement, NOS, 1.36 (1.11-1.66) for Medicare patients where Medicare was administered via a managed care plan, and 1.38 (1.13-1.70) for Medicare patients with a private supplement compared to Medicare, NOS patients. Rurality was not associated with treatment in either model. Conclusions: Significant race/ethnicity, sex, and insurance-based treatment disparities exist amongst Wisconsin pancreatic cancer patients. Future studies should investigate the contribution of social, clinician, and healthcare system factors that impact inequitable access to, inconsistent presentation of, and underutilization of treatment for people of color, women, and publicly insured or uninsured patients. Citation Format: Andrea M. Schiefelbein, Amy K. Taylor, Yana Puckett, Jienian Zhang, John K. Krebsbach, John M. Hampton, Amy Trentham- Dietz, Melissa C. Skala, Sharon M. Weber, John M. Eason, Noelle K. LoConte. Treatment inequity: Examining the influence of race and ethnicity, sex, and insurance on pancreatic cancer care [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-105.

119 Background: Race and ethnicity-based treatment and survival disparities are documented for pancreatic cancer. Studies cite patient genetic, biological, and social factors and differences across treatment centers and geographical areas that may contribute to disparities. We investigated treatment and survival disparities for a cohort of 1,569 pancreatic cancer (PC) patients at the local level within a National Cancer Institute-designated comprehensive cancer center. Methods: Data from 1,569 PC patients aged over 18 diagnosed with adenocarcinoma, NOS or infiltrating duct carcinoma, NOS from 2004 to 2016 who received some or all of their care at the University of Wisconsin Carbone Cancer Center were included in the study. Sequential models of adjusted Cox proportional hazard regression were performed to describe the association between race/ethnicity and overall survival. Model I included age, sex and race/ethnicity; model II added BMI, Charlson Comorbidity Index and stage; model III added rurality, treatment course and payer. Treatment course, defined as the receipt of chemoradiation, surgery with/without chemoradiation, or no treatment, rurality, and insurance status were factors of interest. Results: 38.6% of patients were diagnosed with metastatic disease. Overall survival was 11.6 months. Non-Hispanic black (NHB) patients experienced an 88% increased risk of death (95% CI: 23%-188%) and patients categorized as other race/ethnicity experienced a 32% (10%-60%) increased risk of death compared to NH white (NHW) patients in model II. After adding treatment course and insurance status, the hazard ratio for NHB patients decreased to 1.41 (0.92-2.17) and other race/ethnicity patients decreased to 1.27 (1.05-1.53) compared to NHW Patients. Medicaid patients had an adjusted hazard ratio of 1.41 (1.01-1.95) and unknown/uninsured patients had an adjusted hazard ratio of 1.62 (1.71-4.02) compared to managed care patients. Incarcerated patients had an adjusted hazard ratio of 1.28 (0.98-1.67) compared to managed care patients. Conclusions: To reduce disparities across race/ethnicity and insurance status, organizations should invest in financial support programs for patients in need and monitor treatment courses for people of color, underinsured or uninsured patients to verify access to treatment, equitable treatment, and adherence to treatment guidelines. Future studies should investigate the contribution of clinician and healthcare system bias to race and ethnicity-based cancer disparities.

Surveillance reports consistently observe that cancer mortality rates are higher in rural than urban areas, yet data on the multi-level factors that impact rural disparities have not been fully leveraged to identify the areas of greatest need for research and policy changes. To address gaps in cancer data for rural communities, we adapted the County Health Rankings model of the multiple determinants of health to cancer. Using publicly available data, we compared health factors and cancer mortality for rural versus urban counties in Wisconsin. Counties were defined as rural (N=19) or non-rural (“urban”, N=53) based on Rural Urban Continuum Codes 7-9 and 1-6, respectively. Age-adjusted county-specific cancer mortality rates for all cancer sites combined were obtained from the state cancer registry. Health factor data were obtained from multiple sources in 4 categories: health behaviors (smoking, drinking alcohol, obesity, physical activity); clinical care (HPV vaccination; breast, cervical, and colorectal cancer screening; density of primary care physicians); socioeconomic factors (Area Deprivation Index based on 17 census items); and physical environment (access to grocery stores and alcohol outlets, air quality, pesticide use). Items were ranked for the 72 counties with lower-risk values having better ranks, e.g., higher values for screening and lower values for obesity ranked closer to 1. A composite health factor ranking was defined using County Health Rankings weights, equal to 0.3*(behavioral factors) + 0.2*(clinical factors) + 0.4*(socioeconomic factors) + 0.1*(physical environment). Cancer death rates were higher in rural than in urban counties (181 vs 164 per 100,000). The composite health ranking was positively associated with cancer mortality rates (Pearson correlation coefficient 0.38, 95% CI 0.17-0.57), with worse rankings for rural (average 44, interquartile range, IQR 39-51) than for urban counties (average 34, IQR 25-42). The difference in health factor category rankings between rural and urban counties was greatest for socioeconomic factors (rural average rank 50 vs urban average rank 32) followed by clinical care (rural average rank 43 vs urban average rank 34) and behavioral factors (rural average rank 40 vs urban average rank 35). Physical environment factor rankings were slightly better for rural (average 33) than urban (average 37) counties. In conclusion, we confirmed that cancer mortality in Wisconsin is higher in rural as compared with urban areas. Future analyses will (a) refine the set of health factors used to construct the composite health factor ranking (e.g., account more fully for distance to care) and (b) optimize the weights applied to the categories to calculate the composite ranking. These initial findings suggest that, to increase the impact of future research and policy efforts, clinical and behavioral interventions targeting cancer health disparities in rural counties should include strategies to address socioeconomic factors. Citation Format: Amy Trentham-Dietz, Noelle K LoConte, Betsy Rolland, Lisa Cadmus-Bertram, Tracy M Downs, John M Eason, Cody M Fredrick, John M Hampton, Xiao Zhang, Ronald E Gangnon. Associations between multilevel health factors and cancer mortality according to rural residence [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D002.

PURPOSE: Heavy metals and other elements may act as breast carcinogens due to estrogenic activity. We investigated associations between urine concentrations of a panel of elements and breast density. METHODS: Mammographic density categories were abstracted from radiology reports of 725 women aged 40–65 years in the Avon Army of Women. A panel of 27 elements was quantified in urine using high resolution magnetic sector inductively coupled plasma mass spectroscopy. We applied LASSO (least absolute shrinkage and selection operator) logistic regression to the 27 elements and calculated odds ratios (OR) and 95% confidence intervals (CI) for dense versus non-dense breasts, adjusting for potential confounders. RESULTS: Of the 27 elements, only magnesium (Mg) was selected into the optimal regression model. The odds ratio for dense breasts associated with doubling the Mg concentration was 1.24 (95% CI 1.03–1.49). Doubling the calcium-to-magnesium ratio was inversely associated with dense breasts (OR 0.83, 95% CI 0.70–0.98). CONCLUSIONS: Our cross-sectional study found that higher levels of urinary magnesium were associated with greater breast density. Prospective studies are needed to confirm whether magnesium as evaluated in urine is prospectively associated with breast density and, more importantly, breast cancer.

PURPOSE. Women diagnosed with ductal carcinoma in situ (DCIS) often experience adverse changes in health-related behaviors following diagnosis. The impact of health behaviors on long-term quality of life (QoL) in DCIS survivors has not been investigated. METHODS. We examined the association of post-diagnosis body mass index (BMI), physical activity, alcohol, and smoking with QoL among 1,448 DCIS survivors aged 20–74 enrolled in the population-based Wisconsin in Situ Cohort from 1997–2006. Health behaviors and QoL were self-reported during biennial post-diagnosis interviews. Physical and mental QoL were measured using the validated SF-36 questionnaire. Generalized linear regression was used to determine the association between behaviors and QoL with adjustment for confounders. Lagged behavior variables were used to predict QoL during follow-up and avoid reverse causation. RESULTS. Women reported 3,536 QoL observations over an average 7.9 years of follow-up. Women maintaining a healthy BMI had on average a significantly higher summary measure score of physical QoL than obese women (normal vs. obese: β = 3.02; 2.18, 3.85). Physical QoL scores were also elevated among those who were physically active (5+ hours/week vs. none: β = 1.96; 0.72, 3.20), those consuming at least 7 drinks/week of alcohol (vs. none; β = 1.40; 0.39, 2.41), and non-smokers (vs. current smokers: β = 1.80; 0.89, 2.71). Summary measures of mental QoL were significantly higher among women who were moderately physically active (up to 2 hours/week vs. none: β = 1.11; 0.30, 1.92) and non-smokers (vs. current smokers: β = 1.49;0.45, 2.53). CONCLUSIONS. Our results demonstrate that maintaining healthy behaviors following DCIS treatment is associated with modest improvements in long-term QoL. These results inform interventions aimed at promoting healthy behaviors and optimizing QoL in DCIS survivors.

Purpose To assess the association between geographic access to mammography facilities and women's mammography utilization frequency. Methods Using data from the population-based 1995–2007 Wisconsin Women's Health study, we used proportional odds and logistic regression to test whether driving times to mammography facilities and the number of mammography facilities within 10 km of women's homes were associated with mammography frequency among women aged 50–74 years and whether associations differed between Rural-Urban Commuting Areas and income and education groups. Results We found evidence for nonlinear relationships between geographic access and mammography utilization (nonlinear effects of driving times and facility density, P -values .01 and .005, respectively). Having at least one nearby mammography facility was associated with greater mammography frequency among urban women (1 vs. 0 facilities, odds ratio 1.26, 95% confidence interval, 1.09–1.47), with similar effects among rural women. Adding more facilities had decreasing marginal effects. Long driving times tended to be associated with lower mammography frequency. We found no effect modification by income, education, or urbanicity. In rural settings, mammography nonuse was higher, facility density smaller, and driving times to facilities were longer. Conclusions Having at least one mammography facility near one's home may increase mammography utilization, with decreasing effects per each additional facility.

Background: Little information exists on lifestyle factors that affect prognosis after treatment for ductal carcinoma in situ (DCIS) breast cancer. Improved understanding of the role of lifestyle factors is important to survivors wishing to reduce their risk of a second breast cancer diagnosis. Methods: We examined the association between body mass index (BMI), physical activity, and alcohol intake, and risk of a second breast cancer diagnosis among 1,925 DCIS survivors in the Wisconsin In Situ Cohort. Exposures were self-reported during biennial patient interviews. Second breast cancer diagnoses were validated via pathology report. Cox proportional hazards regression was used to estimate the association between prediagnosis, postdiagnosis, and change in exposure levels and the risk of a second diagnosis, with adjustment for patient, tumor, and treatment factors. Results: Over a mean of 6.7 years of follow-up, 162 second breast cancer diagnoses were reported, including 57 invasive events, 60 in situ events, and 45 diagnoses of unknown stage. A significant trend of increasing risk of a second diagnosis was found over increasing categories of postdiagnosis alcohol intake (Ptrend = 0.02). Among premenopausal women, increased prediagnosis BMI was associated with a reduced risk of a second diagnosis (HR = 0.93; 95% confidence interval, 0.88–0.99). Conclusion: DCIS survivors may reduce their risk of a second diagnosis by reducing postdiagnosis alcohol consumption. Impact: The population of DCIS survivors is projected to surpass one million by the year 2016. Our results suggest that these women may be able to reduce their risk of a second diagnosis through moderation of alcohol consumption. Cancer Epidemiol Biomarkers Prev; 23(3); 450–60. ©2014 AACR.

6525 Background: Survivors of childhood cancer previously treated with chest radiation face elevated breast cancer risk similar to BRCA1 carriers. Children’s Oncology Group (COG) guidelines recommend annual mammography with breast MRI, yet the benefits and costs of various screening strategies are uncertain. Methods: We used two breast cancer simulation models (Model 1 and 2) from the Cancer Intervention and Surveillance Modeling Network (CISNET) and data from the Childhood Cancer Survivor Study to reflect high breast cancer and competing mortality risks among survivors. We simulated 3 screening strategies: annual mammography with MRI starting at age 25 (COG25), annual MRI starting at 25 (MRI25), and biennial mammography starting at 50 (Mammo50). Performance of mammography+/-MRI was based on published studies in BRCA1/2 carriers who have similar cancer risk. Costs and quality of life weights were based on US averages and published studies. Results: Among a simulated cohort of 25-year-old survivors treated with chest radiation, the lifetime breast cancer mortality risk in the absence of screening was 10-11% across models. Compared to no screening, Mammo50, MRI25, and COG25 screening avert approximately 23-25%, 56-62% and 56-71% of deaths, respectively; averted deaths for COG25 compared to MRI25 were higher in Model 1 than Model 2 (9% vs. 50% of breast cancer deaths and is cost-effective. Additional data on test performance are needed to inform recommendations on screening modality. [Table: see text]

Purpose: Genome wide association studies have identified common single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Many of these SNPs have an unknown biologic significance. Hormonal risk factors may mediate the relationships between these loci and breast cancer risk. We explored the relation between breast cancer susceptibility loci and menstrual factors using data from two population-based studies. Methods: In the first dataset, composed of 1328 women ages 20–74 years without a breast cancer diagnosis who participated in an established population-based study conducted in three U.S. states, we used linear regression to assess the associations between 13 previously-identified breast cancer loci with age at menarche, age at natural menopause and the reproductive lifespan. The reproductive lifespan is defined as the time between age at menarche and age at natural menopause, excluding time for pregnancy, oral contraceptive use and lactation. A polygenic risk score created as the sum of the number of risk allele copies in the SNPs was also evaluated for an association with menstrual traits. Significant results were then evaluated in the second dataset comprised of 1353 women ages 43–86 years recruited as part of a cohort study based in Beaver Dam, WI. Results: Polygenic score and 13 loci were not associated with either age at menarche or reproductive lifespan. Two SNPs were associated with age at natural menopause; each increase in the number of copies of the minor allele (A) of rs17468277 (CASP8) was associated with a 1.12 year decrease in age at natural menopause (p = 0.02). The minor allele (G) of SNP rs10941679 (5p12) (p = 0.01) was associated with a 1.01 year increase in age at natural menopause, although these results were not replicated in the follow-up study (p = 0.14 and 0.98, respectively). Conclusions: We did not find evidence to support the hypothesis that breast cancer susceptibility loci are related to menstrual factors. The following are the 18 highest scoring abstracts of those submitted for presentation at the 37th Annual ASPO meeting held March 10–12, 2013, in Memphis, TN.

We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1,484 breast cancer cases and 1,307 controls who participated in a population-based case-control study conducted in three US states. A polygenic score was created as the sum of risk allele copies multiplied by the corresponding log odds estimate. Logistic regression was used to test the associations between SNPs, the score, reproductive and menstrual factors, and breast cancer risk. Nonlinearity of the score was assessed by the inclusion of a quadratic term for polygenic score. Interactions between the aforementioned variables were tested by including a cross-product term in models. We confirmed associations between rs13387042 (2q35), rs4973768 (SLC4A7), rs10941679 (5p12), rs2981582 (FGFR2), rs3817198 (LSP1), rs3803662 (TOX3), and rs6504950 (STXBP4) with breast cancer. Women in the score's highest quintile had 2.2-fold increased risk when compared to women in the lowest quintile (95 % confidence interval: 1.67-2.88). The quadratic polygenic score term was not significant in the model (p = 0.85), suggesting that the established breast cancer loci are not associated with increased risk more than the sum of risk alleles. Modifications of menstrual and reproductive risk factors associations with breast cancer risk by polygenic score were not observed. Our results suggest that the interactions between breast cancer susceptibility loci and reproductive factors are not strong contributors to breast cancer risk.

Objective Genomewide association studies have consistently found variants in fibroblast growth factor receptor 2 (FGFR2) to be associated with breast cancer. Recent reports suggest that postmenopausal hormone therapy (HT) use may modify the association between single nucleotide polymorphisms (SNPs) in FGFR2 and breast cancer risk. We assessed the hypothesis that the association between rs1219648 (FGFR2) SNP and breast cancer risk is modified by postmenopausal HT use in a population-based case-control study. Methods We evaluated rs1219648 SNP for an association with breast cancer risk using data obtained from 869 postmenopausal breast cancer cases diagnosed between 1995 and 2000 and from 808 postmenopausal community controls who participated in a study conducted in three US states. Detailed postmenopausal HT information was collected through a structured telephone interview, and DNA samples were collected by mail using an established mouthwash protocol. Odds ratios and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for age and state of residence. Results We observed a significant association between rs1219648 and breast cancer risk (per-allele odds ratio, 1.22; 95% CI, 1.06-1.41; P = 0.007), which did not vary significantly by ever use of estrogen plus progestogen therapy (interaction P = 0.48). There was stronger evidence of an interaction between ever use of estrogen-only HT and increasing number of rs1219648 risk alleles to increase breast cancer risk (interaction P = 0.08). Conclusions Our results are consistent with a risk association with FGFR2 but provide limited support for interaction with HT use. The study raises the possibility that the FGFR2 rs1219648 variant is more strongly associated with risk in estrogen-only hormone users, although this observation needs to be examined in larger studies.

Objective To determine whether rural residents were at a disadvantage compared with urban residents with regard to the receipt of curative therapy for prostate cancer. Materials and Methods Using the Breast and Prostate Cancer Data Quality and Patterns of Care Study II, patients with prostate cancer who were diagnosed in 2004 were identified. Registrars reviewed the medical records of randomly selected patients with incident prostate cancer (n = 1906). The patients' residential address was geocoded and linked to the census tract from the 2000 U.S. Census. The place of residence was defined as rural or nonrural according to the census tract and rural-urban commuting area categorization. The distance from the residence to the nearest radiation oncology facility was calculated. The odds ratio and 95% confidence intervals associated with receipt of noncurative treatment was calculated from logistic regression models and adjusted for several potential confounders. Results Of the incident patients, 39.1% lived in urban census tracts, 41.5% lived in mixed tracts, and 19.4% lived in rural tracts. Hormone-only or active surveillance was received by 15.4% of the patients. Relative to the urban patients, the odds ratio for noncurative treatment was 1.01 (95% confidence interval 0.59-1.74) for those living in mixed tracts and 0.96 (95% confidence interval 0.52-1.77) for those living in rural tracts. No association was found for noncurative treatment according to the Rural-Urban Commuting Area categorization. The linear trend was null between noncurative treatment and the distance to nearest radiation oncology facility (P = .92). Conclusion The choice of curative treatment did not significantly depend on the patient's place of residence, suggesting a lack of geographic disparity for the primary treatment of prostate cancer.

Purpose Cigarette smoking increases overall mortality, but it is not established whether smoking is associated with breast cancer prognosis. Methods We evaluated the association between smoking status before and after breast cancer diagnosis and mortality in the Collaborative Breast Cancer and Women’s Longevity Study, a population-based prospective observational study conducted in Wisconsin, New Hampshire, and Massachusetts. Participants included 20,691 women, ages 20 to 79 years, diagnosed with incident localized or regional invasive breast cancer between 1988 and 2008; a subset of 4,562 of these women were recontacted a median of 6 years after diagnosis. Hazard ratios (HRs) with 95% CIs were calculated according to smoking status for death as a result of breast cancer; cancers of the lung, pharynx, or intrathoracic organs; other cancer; respiratory disease; and cardiovascular disease. Results During a median of 12 years, 6,778 women died, including 2,894 who died as a result of breast cancer. Active smokers 1 year before breast cancer diagnosis were more likely than never smokers to die of breast cancer (HR, 1.25; 95% CI, 1.13 to 1.37), respiratory cancer (HR, 14.48; 95% CI, 9.89 to 21.21), other respiratory disease (HR, 6.02; 95% CI, 4.55 to 7.97), and cardiovascular disease (HR, 2.08; 95% CI, 1.80 to 2.41). The 10% of women who continued to smoke after diagnosis were more likely than never smokers to die of breast cancer (HR, 1.72; 95% CI, 1.13 to 2.60). When compared with women who continued to smoke after diagnosis, those who quit smoking after diagnosis had lower mortality from breast cancer (HR, 0.67; 95% CI, 0.38 to 1.19) and respiratory cancer (HR, 0.39; 95% CI, 0.16 to 0.95). Conclusion Smoking before or after diagnosis was associated with a higher mortality from breast cancer and several other causes.

Purpose Alcohol intake is associated with increased risk of breast cancer. In contrast, the relation between alcohol consumption and breast cancer survival is less clear. Patients and Methods We assessed pre- and postdiagnostic alcohol intake in a cohort of 22,890 women with incident invasive breast cancer who were residents of Wisconsin, Massachusetts, or New Hampshire and diagnosed from 198 to 200 at ages 20 to 79 years. All women reported on prediagnostic intake; a subsample of 4,881 reported on postdiagnostic intake. Results During a median follow-up of 11.3 years from diagnosis, 7,780 deaths occurred, including 3,484 resulting from breast cancer. Hazard ratios (HR) and 95% CIs were estimated. Based on a quadratic analysis, moderate alcohol consumption before diagnosis was modestly associated with disease-specific survival (compared with nondrinkers, HR = 0.93 [95% CI, 0.85 to 1.02], 0.85 [95% CI, 0.75 to 0.95], 0.88 [95% CI, 0.75 to 1.02], and 0.89 [95% CI, 0.77 to 1.04] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Alcohol consumption after diagnosis was not associated with disease-specific survival (compared with nondrinkers, HR = 0.88 [95% CI, 0.61 to 1.27], 0.80 [95% CI, 0.49 to 1.32], 1.01 [95% CI, 0.55 to 1.87], and 0.83 [95% CI, 0.45 to 1.54] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Results did not vary by beverage type. Women consuming moderate levels of alcohol, either before or after diagnosis, experienced better cardiovascular and overall survival than nondrinkers. Conclusion Overall alcohol consumption before diagnosis was not associated with disease-specific survival, but we found a suggestion favoring moderate consumption. There was no evidence for an association with postdiagnosis alcohol intake and breast cancer survival. This study, however, does provide support for a benefit of limited alcohol intake for cardiovascular and overall survival in women with breast cancer.

© 2016 American College of Physicians.Background: Biennial screening is generally recommended for average-risk women aged 50 to 74 years, but tailored screening may provide greater benefits. Objective: To estimate outcomes for various screening intervals after age 50 years based on breast density and risk for breast cancer. Design: Collaborative simulation modeling using national incidence, breast density, and screening performance data. Setting: United States. Patients: Women aged 50 years or older with various combinations of breast density and relative risk (RR) of 1.0, 1.3, 2.0, or 4.0. Intervention: Annual, biennial, or triennial digital mammography screening from ages 50 to 74 years (vs. no screening) and ages 65 to 74 years (vs. biennial digital mammography from ages 50 to 64 years). Measurements: Lifetime breast cancer deaths, life expectancy and quality-adjusted life-years (QALYs), false-positive mammograms, benign biopsy results, overdiagnosis, cost-effectiveness, and ratio of false-positive results to breast cancer deaths averted. Results: Screening benefits and overdiagnosis increase with breast density and RR. False-positive mammograms and benign results on biopsy decrease with increasing risk. Among women with fatty breasts or scattered fibroglandular density and an RR of 1.0 or 1.3, breast cancer deaths averted were similar for triennial versus biennial screening for both age groups (50 to 74 years, median of 3.4 to 5.1 vs. 4.1 to 6.5 deaths averted; 65 to 74 years, median of 1.5 to 2.1 vs. 1.8 to 2.6 deaths averted). Breast cancer deaths averted increased with annual versus biennial screening for women aged 50 to 74 years at all levels of breast density and an RR of 4.0, and those aged 65 to 74 years with heterogeneously or extremely dense breasts and an RR of 4.0. However, harms were almost 2-fold higher. Triennial screening for the average-risk subgroup and annual screening for the highest-risk subgroup cost less than $100 000 per QALY gained. Limitation: Models did not consider women younger than 50 years, those with an RR less than 1, or other imaging methods. Conclusion: Average-risk women with low breast density undergoing triennial screening and higher-risk women with high breast density receiving annual screening will maintain a similar or better balance of benefits and harms than average-risk women receiving biennial screening.

Introduction: Epidemiologic and laboratory evidence implicates cadmium and other metals as potential breast carcinogens, perhaps due to estrogenic activity. We investigated whether 27 metals were a...

Women diagnosed with ductal carcinoma in situ (DCIS) of the breast are at greater risk of dying from cardiovascular disease and other causes than from breast cancer, yet associations between health-related behaviors and mortality outcomes after DCIS have not been well studied. We examined the association of body mass index, physical activity, alcohol consumption, and smoking with mortality among 1925 women with DCIS in the Wisconsin In Situ Cohort study. Behaviors were self-reported through baseline interviews and up to three follow-up questionnaires. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality after DCIS, with adjustment for patient sociodemographic, comorbidity, and treatment factors. Over a mean of 6.7 years of follow-up, 196 deaths occurred. All-cause mortality was elevated among women who were current smokers 1 year prior to diagnosis (HR = 2.17 [95% CI 1.48, 3.18] vs. never smokers) and reduced among women with greater physical activity levels prior to diagnosis (HR = 0.55 [95% CI: 0.35, 0.87] for ≥5 h per week vs. no activity). Moderate levels of post-diagnosis physical activity were associated with reduced all-cause mortality (HR = 0.31 [95% CI 0.14, 0.68] for 2–5 h per week vs. no activity). Cancer-specific mortality was elevated among smokers and cardiovascular disease mortality decreased with increasing physical activity levels. There are numerous associations between health-related behaviors and mortality outcomes after a DCIS diagnosis. Women diagnosed with DCIS should be aware that their health-related behaviors are associated with mortality outcomes.

Some forms of estrogen are associated with breast cancer risk as well as with mammographic density (MD), a strong marker of breast cancer risk. Whether phytoestrogen intake affects breast density, however, remains unclear. We evaluated the association between serum levels of phytoestrogens and MD in postmenopausal women. We enrolled 269 women, ages 55–70 yr, who received a screening mammogram and had no history of postmenopausal hormone use. Subjects completed a survey on diet and factors related to MD and provided a blood sample for analysis of 3 phytoestrogens: genistein, daidzein, and coumestrol. We examined whether mean percent MD was related to serum level of phytoestrogens, adjusting for age and body mass index. Genistein and daidzein levels correlated with self-reported soy consumption. Mean percent MD did not differ across women with different phytoestrogen levels. For example, women with nondetectable genistein levels had mean density of 11.0% [95% confidence intervals (CI) = 9.9–12.4], compared to 10.5% (95% CI = 8.0–13.7) and 11.2% (95% CI = 8.7–14.6) for < and ≥median detectable levels, respectively. In a population with relatively low soy intake, serum phytoestrogens were not associated with mammographic density. Additional studies are needed to determine effects of higher levels, particularly given patterns of increasing phytoestrogen intake.

Pregnancy complications and poor birth outcomes can affect the survival and long-term health of children. The preconception period represents an opportunity to intervene and improve outcomes; however little is known about women’s mental health prior to pregnancy as a predictor of such outcomes. We sought to determine if and to what extent women’s preconception mental health status impacted subsequent pregnancy complications, non-live birth, and birth weight using a nationally representative, population-based sample. We used pooled 1996-2006 data from the nationally-representative Medical Expenditure Panel Survey (MEPS). Poor preconception mental health was defined as women’s global mental health rating of “fair” or “poor” before conception. Logistic regression was used to assess the association between preconception mental health and pregnancy complications, non-live birth, and having a low birth weight baby within the follow up period. Poor preconception mental health was associated with increased odds of experiencing any pregnancy complication (AOR 1.40, 95% CI: 1.02-1.92), having a non-live birth (AOR 1.48, 95% CI: 0.96-2.27), and having a low birth weight baby (AOR 1.99, 95% CI: 1.00-3.98), all controlling for maternal age, race/ethnicity, marital status, education, health insurance status, income, and number of children in the household. Significant racial and ethnic disparities exist for pregnancy complications and non-live births, but not for low birth weight. Women’s preconception mental health is a modifiable risk factor that stands to reduce the incidence of adverse pregnancy complications and birth outcomes.

Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20–79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06 to 1.87, P-trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35 to 2.32, P-trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis.

Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) can reduce breast cancer incidence by up to 50%, but less is known about its effects on breast cancer-specific and total mortality. Ovarian suppression is an accepted treatment for premenopausal breast cancer that may improve disease-free and overall survival. Prediagnosis TAHBSO may similarly reduce breast cancer mortality rates. However, all-cause mortality among women with breast cancer could be adversely affected by increases in deaths due to heart disease, stroke, or bone fracture that may be associated with TAHBSO. To examine associations between prediagnosis TAHBSO, estrogen therapy, and mortality after breast cancer, we analyzed data from a cohort of 9,215 women ages 50-79 who were diagnosed with invasive breast cancer during 1989-2003 in Wisconsin, Massachusetts, or New Hampshire. Causes and dates of death through 2006 were obtained from the National Death Index. To account for non-breast cancer deaths as competing events, we fit proportional cumulative incidence associated subhazards regression models for breast cancer-specific mortality. Cox proportional hazards regression was used to calculate multivariate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality. Cox regression models were stratified on study center, year of interview, and age at diagnosis and adjusted for body mass index, smoking status, family history of breast cancer and stage at diagnosis as potential confounders. Over an average 8.3 years of follow-up, 2,715 deaths were observed, including 1,507 breast cancer deaths. In total, 1,718 women (18.6%) reported TAHBSO prior to breast cancer diagnosis; while 5,937 women (64.4%) had an intact uterus and ovaries at diagnosis. Compared to women with an intact uterus and ovaries who never used postmenopausal hormones, the subhazard ratio for breast cancer-specific mortality was 0.92 for women who had intact uterus and ovaries and reported using estrogen therapy (95% CI: 0.66, 1.28), 0.71 for women who reported TAHBSO and never used hormones (95% CI: 0.54, 0.95), and 0.93 for women who reported TAHBSO and estrogen use (95% CI: 0.75, 1.16). In contrast, a reduction in all-cause mortality associated with TAHBSO was observed for women who reported estrogen therapy use. Compared to women with an intact uterus and ovaries who never used estrogens, the HR for all-cause mortality among estrogen users who had not undergone TAHBSO was 0.92 (95% CI: 0.73, 1.16), 0.87 for women who reported TAHBSO but no hormone use (95% CI: 0.74, 1.04), and 0.77 among women who reported TAHBSO and estrogen use (95% CI: 0.64, 0.92). Limitations to this analysis included missing information on hormone receptor status and treatment regimens. In these data, prediagnosis TAHBSO was associated with reduced breast cancer-specific mortality among women who never used hormones, and reduced all-cause mortality among estrogen users. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-04.

Purpose The aim of this study was to assess the post-diagnosis use of antidepressants and non-steroidal anti-inflammatory drugs (NSAIDs) in relation to all-cause, breast cancer, and cardiovascular disease (CVD) mortality among long-term breast cancer survivors. Methods A cohort of 3058 breast cancer survivors, who previously participated in a series of case-control studies diagnosed between 1988 and 1999 in Wisconsin. Cancer survivors completed a self-administered mailed follow-up questionnaire in 1998–2001 that addressed use of medications post-diagnosis, including antidepressants and NSAIDs. Vital status information was obtained through the National Death Index through 31 December 2006. We used multivariable Cox proportional hazards modeling to estimate hazard ratios and 95% confidence intervals (CI). Results We identified 463 deaths due to all-causes, 163 due to breast cancer, and 93 due to CVD during follow-up. Among women who had used any antidepressant after a breast cancer diagnosis, there was an increased risk of all-cause (adjusted HR = 1.50, 95%CI: 1.12−2.02) and CVD mortality (HR = 2.42, 95%CI: 1.21−4.83), but not breast cancer mortality (HR = 0.93, 95%CI: 0.55−1.56). The use of NSAIDs after diagnosis was not associated with all-cause (HR = 0.87, 95%CI: 0.69−1.18), breast cancer mortality (HR = 0.69, 95%CI: 0.44−1.10), or CVD (HR = 0.97, 95%CI: 0.57−1.65). Conclusions The use of antidepressants or NSAIDS was not related to breast cancer mortality in long-term breast cancer survivors. In these women, however, antidepressants may increase the risk of all-cause mortality. Copyright © 2010 John Wiley & Sons, Ltd.

BACKGROUND: Women who live in geographic areas with high poverty rates and low levels of education experience poorer survival after a breast cancer diagnosis than women who live in communities with indicators of high socioeconomic status (SES). However, very few studies have examined individual-level SES in relation to breast cancer survival or have assessed the contextual role of community-level SES independent of individual-level SES. METHODS: The authors of this report examined both individual-level and community-level SES in relation to breast cancer survival in a population-based cohort of women ages 20 to 69 years who were diagnosed with breast cancer in Wisconsin between 1995 and 2003 (N = 5820). RESULTS: Compared with college graduates, women who had no education beyond high school were 1.39 times more likely (95% confidence interval [CI], 1.10-1.76) to die from breast cancer. Women who had household incomes

Identification of increasing numbers of breast cancer risk variants holds promise to improve risk prediction and identify population subgroups that could benefit from targeted prevention and early detection. We aimed to examine whether women with increased polygenic risk are more likely to be diagnosed with symptomatic breast cancer. A case-control study including data collected from interviews, DNA from saliva, and cancer registry data collected between 2001-2007 (4,315 cases, 3,919 controls) was used to construct a polygenic risk score (PRS). Single nucleotide polymorphisms (SNPs, N=98) were selected from recently published genome-wide association studies of breast cancer and breast density, and comparative rat genome studies. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) associated with the SNPs. SNPs with p-values ≤0.10 (N=24) were used to construct quintiles of the PRS by multiplying the log-odds of the SNPs by the number of risk alleles; multivariable logistic regression models evaluated all women and strata of women defined by method of detection and stage at diagnosis. Odds ratios were adjusted for age, family history of breast cancer, age at menopause/menopausal status, body mass index, parity, and age at first birth. Overall, PRS quintile categories were associated with breast cancer risk in a dose response manner (Q1: OR=1, reference; Q2 OR=1.36, 95% CI 1.16-1.58; Q3 OR=1.66, 95% CI 1.43-1.93; Q4 OR=1.83, 95% CI 1.58-2.12; Q5 OR=2.58, 95% CI 2.23-2.98). Evaluated on a continuous scale, the PRS was associated with an OR=1.38 for a 1-unit change in the standard deviation (SD), 95% CI 1.32-1.45. Odds ratios were essentially unchanged when stratified by method of detection (p-value=0.40). The odds ratio of breast cancer associated with the continuous PRS was elevated among women diagnosed with advanced breast cancer: DCIS, OR=1.36, 95% CI 1.26-1.47 per 1 SD; localized OR=1.37, 95% CI 1.30-1.45 per 1 SD; regional OR=1.38, 95% CI 1.28-1.48 per 1 SD; and distant OR=1.82, 95% CI 1.39-2.40. These results suggest that polygenic risk scores are strongly related to breast cancer risk, that the association does not vary by method of breast cancer detection, but that the association is strongest for metastatic breast cancer. Citation Format: Amy Trentham-Dietz, John M. Hampton, Irene M. Ong, C David Page, Michael N. Gould, Jill D. Haag, Polly A. Newcomb, James D. Shull, Elizabeth S. Burnside. Polygenic risk score, stage, and mode of detection in relation to breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3257.

Evidence has been inconsistent regarding the impact of social networks on survival after breast cancer diagnosis. We prospectively examined the relation between components of social integration and survival in a large cohort of breast cancer survivors.Women (N=4,589) diagnosed with invasive breast cancer were recruited from a population-based, multi-center, case-control study. A median of 5.6 years (Interquartile Range 2.7-8.7) after breast cancer diagnosis, women completed a questionnaire on recent post-diagnosis social networks and other lifestyle factors. Social networks were measured using components of the Berkman-Syme Social Networks Index to create a measure of social connectedness. Based on a search of the National Death Index, 552 deaths (146 related to breast cancer) were identified. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression.Higher scores on a composite measure of social connectedness as determined by the frequency of contacts with family and friends, attendance of religious services, and participation in community activities was associated with a 15-28% reduced risk of death from any cause (p-trend=0.02). Inverse trends were observed between all-cause mortality and frequency of attendance at religious services (p-trend=0.0001) and hours per week engaged in community activities (p-trend=0.0005). No material associations were identified between social networks and breast cancer-specific mortality.Engagement in activities outside the home was associated with lower overall mortality after breast cancer diagnosis.

Bisphosphonates are commonly prescribed for the prevention and treatment of osteoporosis (Rosen, 2005). By inhibiting bone resorption, bisphosphonate therapy also reduces skeletal complications from bone involvement in breast, prostate, and other cancers, and from the bone-depleting consequences of some treatments (Berenson et al, 1996; Aapro et al, 2008; Saad et al, 2008). In addition to the reduction in osteoclastic bone resorption, the more potent aminobisphosphonates inhibit the mevalonate pathway, thereby affecting cell function and survival(Luckman et al, 1998; Dunford et al, 2001). As this pathway leads to the prenylation of key signalling proteins required by all cells, aminobisphosphonates may affect the viability of other cell types, such as tumours (Russell et al, 1999; Caraglia et al, 2006). Nitrogen-containing bisphosphonates have also been shown to directly induce tumour apoptosis, inhibit angiogenesis, and prevent tumour cell adhesion (Neville-Webbe et al, 2002; Wood et al, 2002). These anti-proliferative actions may be relevant to the development of a broad range of cancers, including breast neoplasms(Green, 2003; Winter et al, 2008). We examined the association between bisphosphonate use and breast cancer in a population-based case–control study.

ObjectiveMultivitamin supplements are used by nearly half of middle-aged women in the USA. Despite this high prevalence of multivitamin use, little is known about the effects of multivitamins on health outcomes, including cancer risk. Our main objective was to determine the association between multivitamin use and the risk of breast cancer in women.DesignWe conducted a population-based case–control study among 2968 incident breast cancer cases (aged 20–69 years), diagnosed between 2004 and 2007, and 2982 control women from Wisconsin, USA. All participants completed a structured telephone interview which ascertained supplement use prior to diagnosis, demographics and risk factor information. Odds ratios and 95 % confidence intervals were calculated using multivariable logistic regression.ResultsCompared with never users of multivitamins, the OR for breast cancer was 1·02 (95 % CI 0·87, 1·19) for current users and 0·99 (95 % CI 0·74, 1·33) for former users. Further, neither duration of use (for ≥10 years: OR = 1·13, 95 % CI 0·93, 1·38,Pfor trend = 0·25) nor frequency (>7 times/week: OR = 1·00, 95 % CI 0·77, 1·28,Pfor trend = 0·97) was related to risk in current users. Stratification by menopausal status, family history of breast cancer, age, alcohol, tumour staging and postmenopausal hormone use did not significantly modify the association between multivitamin use and breast cancer.ConclusionsThe current study found no association between multivitamin supplement use and breast cancer risk in women.

Maternal depression is often untreated, resulting in serious consequences for mothers and their children. Factors associated with receipt of adequate treatment for depression were examined in a population-based sample of 2,130 mothers in the USA with depression using data from the 1996-2005 Medical Expenditure Panel Survey. Chi-squared analyses were used to evaluate differences in sociodemographic and health characteristics by maternal depression treatment status (none, some, and adequate). Multivariate regression was used to model the odds of receiving some or adequate treatment, compared to none. Results indicated that only 34.8% of mothers in the USA with depression received adequate treatment. Mothers not in the paid workforce and those with health insurance were more likely to receive treatment, while minority mothers and those with less education were less likely to receive treatment. Understanding disparities in receipt of adequate treatment is critical to designing effective interventions, reducing treatment inequities, and ultimately improving the mental health and health of mothers and their families.

Certain classes of vitamins and nutrients found in fruits and vegetables have been of particular interest in relation to cancer prevention, owing to their potential anticarcinogenic properties. We examined the association between certain fruits, vegetables, carotenoids, and vitamin A and breast cancer risk in a large population-based case-control study of women residing in the states of Massachusetts, New Hampshire and Wisconsin. The study was comprised of 5,707 women with incident invasive breast cancer (2,363 premenopausal women and 3,516 postmenopausal women) and 6,389 population controls (2,594 premenopausal women and 3,516 postmenopausal women). In an interview, women were asked about their intake of carotenoid rich fruits and vegetables 5 years prior to a referent date. An inverse association observed among premenopausal women was for high levels of vitamin A (OR: 0.82, 95% CI: 0.68-0.98, p for trend = 0.01), beta-carotene (OR: 0.81, 95% CI 0.68-0.98, p for trend = 0.009), alpha-carotene (OR: 0.82, 95% CI: 0.68-0.98, p for trend = 0.07) and lutein/zeaxanthin (OR: 0.83, 95% CI 0.68-0.99, p for trend = 0.02). An inverse association was not observed among postmenopausal women. Among premenopausal women who reported ever smoking, these results were stronger than among never smokers, although tests for interaction were not statistically significant. Results from this study are comparable to previous prospective studies, and suggest that a high consumption of carotenoids may reduce the risk of premenopausal but not postmenopausal breast cancer, particularly among smokers.

Most epidemiologic studies have detected no association between prior use of antidepressant medications and breast cancer risk. Despite the uniform conclusion, there is a continuous rise in the proportion of women using antidepressants, lending support to further monitoring of disease effects.We conducted a population-based case-control study among 2908 incident breast cancer cases diagnosed from 2003 to 2006, and 2927 control women from Wisconsin. Associations between antidepressant use and breast cancer risk were evaluated using multivariable logistic regression.The association between use of antidepressant medications and breast cancer risk was null (OR = 0.89, 95%CI 0.78-1.01). When stratified by type of antidepressant, use of selective-serotonin reuptake inhibitors (SSRIs) resulted in a similar risk overall (OR = 0.85, 95%CI 0.72-1.00) and among former and currents users. There were no associations between other types of antidepressant classes and breast cancer risk. In assessing risks among the five most commonly used antidepressants, we detected no association with fluoxetine, sertraline, venlafaxine, or buproprion hydrochloride. There was a reduction in breast cancer risk of 36% (OR = 0.64, 95%CI 0.45-0.92) among users of paroxetine hydrochloride. When stratified by body mass index, there was a reduction in risk associated with antidepressant users who were not overweight (OR = 0.73, 95% CI 0.60-0.90), but this association was null in overweight women (p-interaction = 0.04).Surveillance of health risks associated with antidepressant medications continues to be of public health importance, though these medications are not likely to be associated with breast cancer risk.

Epidemiologic studies have reported an increased risk of breast cancer among women who drink alcohol, including wine ([1][1], [2][2]) Two meta-analyses estimated a ∼10% [95% confidence interval (CI), 5-15%] increased risk of breast cancer with each additional 10 grams (∼1 drink) of alcohol/day