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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 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.

152 Background: The Hmong people constitute an Asian-American subgroup, accounting for 0.1% of the United States (US) population. Originating from Laos and Vietnam, Hmong individuals fought as secret soldiers for the US during the Vietnam War and later immigrated to the US, with the largest settlements in Minnesota, Wisconsin, and California. The Hmong population has faced various health disparities in the domains of mental health, chronic disease, and cancer. This study seeks to investigate trends in colorectal cancer (CRC) survival in the US Hmong population. Methods: Cases of colon and rectal adenocarcinoma diagnosed between 2004-2017 were identified within the National Cancer Database. Summary statistics of demographic, clinical, socioeconomic, and treatment variables were calculated. Multiple Cox proportional hazard models were constructed using sets of demographic, clinical, socioeconomic, and treatment variables to identify factors associated with overall survival (OS) within the Hmong population diagnosed with CRC. Results: One hundred and twenty (0.01%) Hmong individuals were identified within a total of 881,243 CRC cases. Their average age at diagnosis was 58.9 years, compared 68.7 years for Non-Hispanic White (NHW) individuals (p < 0.01). Over half of Hmong individuals (52.5%) were diagnosed with Stage III or VI disease (NHW, 42.5%, p < 0.03), and they more frequently resided in the lowest median income quartile (p < 0.01), the lowest high school degree achievement quartile (p < 0.01), and had higher rates of Medicaid coverage (p < 0.01) compared to NHWs. When adjusting only for age, sex, stage, and Charlson-Deyo comorbidity score, Hmong individuals had a greater hazard of death compared to their NHW counterparts (HR 1.43, p < 0.01). However, in a multivariable model accounting for all variables suspected to be associated with CRC outcomes, OS was similar between these groups (HR 1.01, p < 0.93). Conclusions: Hmong individuals diagnosed with CRC appear to have similar overall survival to Non-Hispanic Whites despite belonging to lower socioeconomic groups, being diagnosed at a younger age and with a higher proportion of Stage III/VI disease. This may point to a robust response to treatment and resilience within the Hmong community. Future efforts will focus on disseminating this information and developing community-based approaches for health screening and prevention.

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 (

1008 Background: Treatment for metastatic breast cancer has advanced since 2000, but we do not know if those advances have reduced mortality in the general population. Methods: Four Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2017 using national data on mammography use and performance, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, and competing mortality. Models compared overall and ER/HER2-specific breast cancer mortality rates from 2000 to 2017 relative to estimated rates with no screening or treatment, and attributed mortality reductions to screening, early-stage or metastatic treatment. Results of an exemplar model are shown. Results: The mortality reduction attributable to early-stage treatment increased from 35.8% in 2000 to 48.2% in 2017, while the proportion attributable to metastatic treatment decreased slightly from 23.9% to 20.6%. The increasing contribution of early-stage treatment reflects the transition of effective metastatic treatments to early-stage disease: accordingly, ten-year distant recurrence-free survival improved (82.5% in 2000, 87.3% in 2017; for ER+HER2+, 78.2% to 90.9%). Survival time after metastatic diagnosis also increased, doubling from 1.48 years in 2000 to 2.80 years in 2017, with the best survival for women with ER+HER2+ cancers (4.08 years) and worst for ER-HER2- (1.22 years). Conclusions: Advances in metastatic breast cancer treatment are reflected in lower population mortality, both through transition to early-stage treatment and gains for women with metastatic disease. These results may inform patient/physician discussions about breast cancer prognosis and expected benefits of treatment. [Table: see text]

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

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.

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.

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.

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.

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.

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.

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

Meat consumption and heterocyclic amine (HCA) intake have been inconsistently associated with breast cancer risk in epidemiologic studies. Genetic variation in N-acetyltransferase2 (NAT2) has been suggested to modify the association of meat intake with breast cancer through its influence on metabolism of HCAs. We examined associations between meat intake, HCA exposure, acetylator genotype, and breast cancer risk in a case-control study of 2,686 case women and 3,508 controls. Women were asked to report their usual intake, cooking method, and preferred doneness of specific meats. We observed no association between total meat, red meat, or chicken with breast cancer risk. Women who consumed 5 or more servings of meat per week had no increased risk of breast cancer compared to women consuming fewer than 2 servings per week (OR = 0.99, 95% CI 0.84–1.15). No statistically significant associations with breast cancer were found for individual HCAs or for total estimated mutagenic activity of meat. Results varied modestly according to menopausal status. There were no statistically significant interactions with NAT2 genotype. Results do not support an important association of HCAs with breast cancer risk, although potential biases in case-control studies should be considered.

Epidemiologic studies of hormone therapy (HT) and colorectal cancer incidence consistently show an inverse association; however, few studies considered prediagnostic use of HT on mortality among colorectal cancer patients. We evaluated the relationship of HT and survival among a population-based cohort of women with large bowel cancer. Cases (n=1297) were newly diagnosed with invasive cancer of the colon or rectum, aged 40-74 years at diagnosis, who were identified by Wisconsin’s statewide registry (1988-1991; 1997-2001) for two case-control studies. Information on HT use and other colorectal cancer risk factors was collected by standardized interview. There were 507 deaths (274 of these attributable to colorectal cancer) over 8.4 years of follow-up through December 2005. Hormone use was not associated with colorectal cancer mortality (Adjusted hazard rate ratio=1.09, confidence interval=0.81-1.47). Colorectal cancer specific mortality was not associated with HT when considered separately by preparation type or combined. Stage did not modify this relationship. Long-term HT was weakly positively associated with increased mortality after diagnosis of proximal colon, but not distal colon cancer. Because we detected no differences in survival among users of HT compared to non-users, the results suggest that HT use may affect the incidence of only some colorectal tumors.

Previous studies have suggested that physical activity may lower lung cancer risk. The association of physical activity with reduced chronic inflammation provides a potential mechanism, yet few studies have directly related inflammatory markers to cancer incidence. The relation among physical activity, inflammation, and lung cancer risk was evaluated in a prospective cohort of 4,831 subjects, 43 to 86 years of age, in Beaver Dam, Wisconsin. A total physical activity index was created by summing up kilocalories per week from sweat-inducing physical activities, city blocks walked, and flights of stairs climbed. Two inflammatory markers, WBC count and serum albumin, were measured at the baseline examination. During an average of 12.8 years of follow-up, 134 incident cases of lung cancer were diagnosed. After multivariable adjustment, participants in the highest tertile of total physical activity index had a 45% reduction in lung cancer risk compared with those in the lowest tertile (hazard ratio, 0.55; 95% confidence interval, 0.35-0.86). Participants with WBC counts in the upper tertile (≥8 × 103/μL) were 2.81 (95% confidence interval, 1.58-5.01) times as likely to develop lung cancer as those with counts in the lowest tertile (

Background: A few studies have observed reduced breast cancer mortality in women who used hormone therapy before diagnosis. Due to the high prevalence of past and current hormone use, it is important to investigate whether these preparations are related to breast cancer mortality. Methods: To evaluate the influence of prediagnostic use of hormone therapy on breast cancer mortality, a prospective cohort of 12,269 women ages 50 years or more diagnosed with incident invasive breast cancer and residents of Wisconsin, Massachusetts, or New Hampshire were enrolled in three phases beginning in 1988. They were followed for death until December 31, 2005, using the National Death Index. Cumulative mortality and multivariable adjusted hazard rate ratios for breast cancer and other mortality causes were calculated for women according to any hormone therapy use, and for exclusive use of estrogen or estrogen-progestin (EP). Results: During an average 10.3 years of follow-up, 1,690 deaths from breast cancer were documented. Cumulative mortality from breast cancer was lower among hormone therapy users, specifically current users at the time of diagnosis, and EP users, compared with nonusers. Adjusted survival varied by type and duration of hormone therapy before diagnosis. A reduced risk of death from breast cancer was associated with EP preparations (hazard rate ratio, 0.73; 0.59-0.91) and with ≥5 years of EP use (0.60; 0.43-0.84). No association was observed for women who were former or current users of E-alone preparations. Conclusions: Although use of combined EP preparations increases breast cancer risk, in this study, use of these hormones before diagnosis was associated with reduced risk of death after a breast cancer diagnosis. The better survival among users, particularly of EP, persisted after adjustment of screening, stage, and measured confounders. (Cancer Epidemiol Biomarkers Prev 2008;17(4):864–71)

We conducted a population-based case–control study to investigate the association between hormone therapy (HT) and ovarian cancer incidence, and followed all these cancer cases to determine the association of HT use with ovarian cancer mortality. Seven hundred fifty-one incident cases of invasive epithelial ovarian cancer aged 40–79 years were diagnosed in Massachusetts and Wisconsin between 1993–1995 and 1998–2001 and matched to similarly aged controls (n = 5,808). Study subjects were interviewed by telephone, which ascertained information on HT use and specific preparation, estrogen alone (E-alone) or estrogen plus progestin (EP). Ovarian cancer cases were followed-up for mortality through December 2005. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals (CI) for ovarian cancer incidence, and Cox proportional hazards modeling was used to estimate hazard ratios and corresponding confidence intervals for ovarian cancer mortality. Ever use of HT was significantly associated with an increased risk of ovarian cancer (odds ratio 1.57, 95% CI 1.31–1.87). The excess risk was confined to women who used E-alone preparations (OR 2.33, 95% CI 1.85–2.95). No significant associations were detected between pre-diagnosis HT use and ovarian cancer survival. Hormone therapy increases risk of ovarian cancer among E-alone users, but there is no substantial impact on survival after diagnosis.

Purpose Studies of quality of life (QoL) are scarce among survivors of ductal carcinoma in situ (DCIS). The objective of this study was to assess long-term QoL in DCIS survivors in relation to age at diagnosis, time since diagnosis, and treatments received. Methods We assessed physical and mental measures of health-related QoL in 1,604 patients with DCIS diagnosed in 1997 to 2006 with up to four follow-up interviews. We further compared baseline QoL to 1,055 control patients without DCIS. QoL was measured using the validated Medical Outcomes Study Short Form 36 Health Status Survey questionnaire. Among patients with DCIS, we examined trends in QoL over time since diagnosis using generalized linear regression models, adjusting for confounders. We tested for effect modification by surgical treatment choice, post-treatment endocrine therapy use, and age at diagnosis. Results Both physical and mental measures of QoL among DCIS survivors at fewer than 2 years after diagnosis were comparable to controls. Mental measures of QoL among patients with DCIS declined at ≥ 10 years after diagnosis and were significantly lower than at less than 2 years after diagnosis (47.4 v 52.0; P < .01). In the first 5 years after a DCIS diagnosis, mental QoL was significantly higher among women diagnosed at ages 50 to 74 years compared with those diagnosed at ages 28 to 49 years, although this difference was not sustained in later time periods. Conclusion QoL after a DCIS diagnosis was generally comparable to that of women of similar age without a personal history of DCIS. Our findings suggest that DCIS survivors, and particularly those diagnosed at a younger age, may benefit from support for mental QoL.

PurposeInflammatory breast cancer (IBC) is an aggressive subtype of breast cancer for which treatments vary, so we sought to identify factors that affect the receipt of guideline-concordant care.MethodsPatients diagnosed with IBC in 2004 were identified from the Breast and Prostate Cancer Data Quality and Patterns of Care Study, containing information from cancer registries in seven states. Variation in guideline-concordant care for IBC, based on National Comprehensive Cancer Network (NCCN) guidelines, was assessed according to patient, physician, and hospital characteristics.ResultsOf the 107 IBC patients in the study without distant metastasis at the time of diagnosis, only 25.8% received treatment concordant with guidelines. Predictors of non-concordance included patient age (≥70 years), non-white race, normal body mass index (BMI 18.5-25 kg/m(2)), patients with physicians graduating from medical school >15 years prior, and smaller hospital size (

While many reports describe health-related quality of life (QOL) among breast cancer survivors, few compare QOL before and after diagnosis and whether changes in QOL substantially differ from changes experienced by all women during aging. QOL was examined in a cohort of female residents of Beaver Dam, Wisconsin, aged 43-86 years at the time of a 1988-1990 baseline examination (N = 2,762; 83% of eligible). Participants were re-contacted four times through 2002 to ascertain QOL using the 36-item Short Form Health Survey (SF-36). QOL data for 114 incident breast cancer cases identified by data linkage with the statewide cancer registry were compared with data for 2,527 women without breast cancer. Women with breast cancer averaged 4.5 (95% CI: 1.6, 7.3) points lower than control women on the SF-36 Physical Component Summary (PCS) scale, regardless of time since diagnosis (up to 13 years). Women with breast cancer also reported lower scores on the SF-36 Mental Component Summary (MCS) scale within two years after diagnosis, but not at more distant times. In longitudinal analyses, 26 women who completed the SF-36 before and after breast cancer diagnosis experienced larger declines than age-matched controls in seven of the eight SF-36 health domains (all but role-emotional) and reported relative declines of -7.0 (95% CI: -11.5, -2.6) and -2.9 (95% CI: -6.3, 0.6) on the PCS and MCS scales, respectively. These results suggest that breast cancer survivors experience relative declines in health-related QOL across a broad spectrum of domains, even many years after diagnosis.

Whereas germ line missense mutations in the tumor suppressor gene TP53 are associated with a marked predisposition to breast cancer, single-nucleotide polymorphisms (SNPs) may play a more modest role in breast cancer susceptibility. We examined genetic variation in TP53 in relation to breast cancer risk among women aged 20-74 years in a population-based case-control study in Wisconsin, Massachusetts and New Hampshire. Analyses were conducted separately for in situ (176 cases/581 controls) and invasive (1,490 cases/1,291 controls) breast cancer. Oral mucosal DNA samples were genotyped for the codon 72 polymorphism in exon 4 (rs1,042,522), seven intronic SNPs and three SNPs residing in the 3' untranslated region (UTR). Logistic regression was used to obtain age- and state-adjusted odds ratios for individual SNPs. Haplotypes were reconstructed using PHASE software, and the overall association with breast cancer risk was assessed using a global score test. None of the 11 individual SNPs or eight common haplotypes were significantly related to breast carcinoma in situ risk. Among all women, two linked SNPs (D' = 0.99, r(2) = 0.95) on intron 7 (rs12,951,053, rs12,947,788) were associated with modest increases in invasive breast cancer risk; however, associations were only significant for heterozygous carriers. The data suggested that additional variants in the 3' UTR (rs9,894,946), and in two correlated SNPs (D' = 0.94, r(2) = 0.81) in introns 6 (rs1,625,895) and 4 (rs2,909,430), were associated with reduced invasive breast cancer risk among women aged 50 and younger only (P(interaction) < 0.03). These results indicate that common variation in the TP53 gene could modify the risk of invasive breast cancer.