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PURPOSE To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC). RESULTS The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC. CONCLUSION The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.

PURPOSE The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years. METHODS A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs. RESULTS The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in BRCA1, BRCA2, and PALB2 were found in 3.42% of women diagnosed with estrogen receptor (ER)–negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in CHEK2, PALB2, BRCA2, and BRCA1 were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in BRCA1, BRCA2, and PALB2. CONCLUSION This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with BRCA1 and BRCA2 PVs and perhaps with PALB2 and CHEK2 PVs should be considered for magnetic resonance imaging screening.

PURPOSE This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population. METHODS A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in BRCA1, BRCA2, ATM, CHEK2, PALB2, BARD1, BRIP1, CDH1, and NF1. PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor–specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC. RESULTS The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of BRCA1, BRCA2, and PALB2 carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of ATM and CHEK2 carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk. CONCLUSION PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of CHEK2 and nearly half of ATM carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.

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: Recent reports suggest that racial differences in breast cancer incidence rates have decreased. We examined whether these findings apply to breast cancer mortality while considering age, period, and cohort influences on both absolute and relative measures of breast cancer mortality. METHODS: Using publicly available datasets (CDC Wonder, Human Mortality Database), we developed an age-period-cohort model of breast cancer mortality and breast cancer deaths as a proportion of all deaths during 1968–2019 among all women and by five race/ethnicity groups with sufficient numbers for estimation: Hispanic (all races), American Indian/Alaska Native and Asian/Pacific Islanders (regardless of ethnicity), non-Hispanic Black, and non-Hispanic White. RESULTS: Initially increasing after 1968, age-adjusted breast cancer mortality rates have decreased among all racial/ethnic groups since 1988. The age-adjusted percent of all deaths due to breast cancer also has been declining for non-Hispanic White women since about 1990 while increasing or holding steady for other race/ethnic groups. In 2019, the age-adjusted percent of deaths due to breast cancer for women was highest for Asian/Pacific Islanders (5.6%) followed by non-Hispanic Black (4.5%), Hispanic (4.4%), non-Hispanic White (4.1%), and American Indian/Alaska Native women (2.6%). CONCLUSIONS: Breast cancer mortality disparities are now greater on both relative and absolute scales for non-Hispanic Black women, and using the relative scale for Asian/Pacific Islander and Hispanic women, compared with non-Hispanic White women for the first time in 50 years.

Background We assessed the clinical utility of a first-degree breast cancer family history and polygenic risk score (PRS) to inform screening decisions among women aged 30-50 years. Methods Two established breast cancer models evaluated digital mammography screening strategies in the 1985 US birth cohort by risk groups defined by family history and PRS based on 313 single nucleotide polymorphisms. Strategies varied in initiation age (30, 35, 40, 45, and 50 years) and interval (annual, hybrid, biennial, triennial). The benefits (breast cancer deaths averted, life-years gained) and harms (false-positive mammograms, overdiagnoses) were compared with those seen with 3 established screening guidelines. Results Women with a breast cancer family history who initiated biennial screening at age 40 years (vs 50 years) had a 36% (model range = 29%-40%) increase in life-years gained and 20% (model range = 16%-24%) more breast cancer deaths averted, but 21% (model range = 17%-23%) more overdiagnoses and 63% (model range = 62%-64%) more false positives. Screening tailored to PRS vs biennial screening from 50 to 74 years had smaller positive effects on life-years gained (20%) and breast cancer deaths averted (11%) but also smaller increases in overdiagnoses (10%) and false positives (26%). Combined use of family history and PRS vs biennial screening from 50 to 74 years had the greatest increase in life-years gained (29%) and breast cancer deaths averted (18%). Conclusions Our results suggest that breast cancer family history and PRS could guide screening decisions before age 50 years among women at increased risk for breast cancer but expected increases in overdiagnoses and false positives should be expected.

PURPOSE: Physical activity is important for healthy cancer survivorship, yet many endometrial cancer survivors do not participate in recommended muscle-strengthening activity. The purpose of this study was to determine the feasibility of home-based muscle strengthening activity in endometrial cancer survivors. METHODS: Forty post-treatment endometrial cancer survivors were enrolled in a randomized trial, of twice-weekly home-based strength exercise versus wait-list control. The intervention included educational materials, exercise equipment (dumbbells, resistance bands), and support/feedback via video coaching sessions. Participants completed the exercises twice per week for 10 weeks, with a 5-week follow-up period. Feasibility was measured by program adherence, as well as safety of and satisfaction with the study. RESULTS: On average, participants were 60.9 years old (SD = 8.7), had a BMI of 39.9 kg/m(2) (SD = 15.2), and were 2.9 years (SD = 1.2) since diagnosis. The majority (83%) had stage I disease at diagnosis. Seventy-five percent adhered to the exercise prescription of twice/week, with 85% of participants missing fewer than 3 of the workouts. Forty percent of participants continued workouts during the 5-week follow-up. Participants were highly satisfied with intervention. No injuries or adverse everts occurred. CONCLUSION: This home-based program was feasible in endometrial cancer survivors. While adherence was measured, future research should focus on long-term maintenance of exercise and should explore progressions and modifications of exercises at a distance for various abilities. IMPLICATIONS FOR CANCER SURVIVORS: Muscle strengthening activities are recommended for all cancer survivors. This study shows that a home-based muscle strengthening exercise is feasible in endometrial cancer survivors.

BACKGROUND: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants. METHODS: In a population-based case–control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed. RESULTS: Pathogenic variants in 12 established breast cancer–predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor–negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor–positive breast cancer. Pathogenic variants in 16 candidate breast cancer–predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer. CONCLUSIONS: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer–predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.)

Background: There is widespread interest in discriminating indolent from aggressive ductal carcinoma in situ (DCIS). We sought to evaluate collagen organization in the DCIS tumor microenvironment in relation to pathologic characteristics and patient outcomes. Methods: We retrieved fixed tissue specimens for 90 DCIS cases within the population-based Vermont DCIS Cohort. We imaged collagen fibers within 75 μm of the tumor/stromal boundary on hematoxylin and eosin–stained slides using multiphoton microscopy with second-harmonic generation. Automated software quantified collagen fiber length, width, straightness, density, alignment, and angle to the tumor/stroma boundary. Factor analysis identified linear combinations of collagen fiber features representing composite attributes of collagen organization. Results: Multiple collagen features were associated with DCIS grade, necrosis pattern, or periductal fibrosis (P < 0.05). After adjusting for treatments and nuclear grade, risk of recurrence (defined as any second breast cancer diagnosis) was lower among cases with greater collagen fiber width [hazard ratio (HR), 0.57 per one standard deviation increase; 95% confidence interval (CI), 0.39–0.84] and fiber density (HR, 0.60; 95% CI, 0.42–0.85), whereas risk was elevated among DCIS cases with higher fiber straightness (HR, 1.47; 95% CI, 1.05–2.06) and distance to the nearest two fibers (HR, 1.47; 95% CI, 1.06–2.02). Fiber length, alignment, and fiber angle were not associated with recurrence (P > 0.05). Five composite factors were identified, accounting for 72.4% of the total variability among fibers; three were inversely associated with recurrence (HRs ranging from 0.60 to 0.67; P ≤ 0.01). Conclusions: Multiple aspects of collagen organization around DCIS lesions are associated with recurrence risk. Impact: Collagen organization should be considered in the development of prognostic DCIS biomarker signatures.

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 The risks of breast cancer in African American (AA) women associated with inherited mutations in breast cancer predisposition genes are not well defined. Thus, whether multigene germline hereditary cancer testing panels are applicable to this population is unknown. We assessed associations between mutations in panel-based genes and breast cancer risk in 5054 AA women with breast cancer and 4993 unaffected AA women drawn from 10 epidemiologic studies. Methods Germline DNA samples were sequenced for mutations in 23 cancer predisposition genes using a QIAseq multiplex amplicon panel. Prevalence of mutations and odds ratios (ORs) for associations with breast cancer risk were estimated with adjustment for study design, age, and family history of breast cancer. Results Pathogenic mutations were identified in 10.3% of women with estrogen receptor (ER)-negative breast cancer, 5.2% of women with ER-positive breast cancer, and 2.3% of unaffected women. Mutations in BRCA1, BRCA2, and PALB2 were associated with high risks of breast cancer (OR = 47.55, 95% confidence interval [CI] = 10.43 to >100; OR = 7.25, 95% CI = 4.07 to 14.12; OR = 8.54, 95% CI = 3.67 to 24.95, respectively). RAD51D mutations were associated with high risk of ER-negative disease (OR = 7.82, 95% CI = 1.61 to 57.42). Moderate risks were observed for CHEK2, ATM, ERCC3, and FANCC mutations with ER-positive cancer, and RECQL mutations with all breast cancer. Conclusions The study identifies genes that predispose to breast cancer in the AA population, demonstrates the validity of current breast cancer testing panels for use in AA women, and provides a basis for increased referral of AA patients for cancer genetic testing.

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.

Health literacy (HL) and cancer care coordination (CCC) were examined for their relationship to quality of life (QOL) among breast cancer survivors. CCC was hypothesized to have a stronger relationship to QOL for women with lower HL. Women (N = 1138) who had completed treatment for Stage 0–III, ductal carcinoma breast cancer between January 2013 and May 2014 at one of eight large medical centers responded to a mailed questionnaire. Responses to questions about survivorship care planning and presence of professional care coordinator were combined to form an index of CCC. An index of HL was also derived. QOL was measured using the Functional Assessment of Cancer Therapy-Breast (FACT-B) scales. 74.3% (N = 845) of patients reported having a health professional coordinate their care during treatment and 78.8% (N = 897) reported receiving survivorship care planning. CCC was classified as none, partial, or high for 7.1%, 32.7%, and 60.2% of the patients, respectively. Except for emotional well-being, the interaction between HL and CCC was significant for all QOL domains (p

PURPOSE: Endometrial cancer is strongly linked to obesity and inactivity; however, increased physical activity has important benefits even in the absence of weight loss. Resistance (strength) training can deliver these benefits; yet few women participate in resistance exercise. The purpose of this study was to describe both physiological and functional changes following a home-based strength training intervention. METHODS: Forty post-treatment endometrial cancer survivors within 5 years of diagnosis were enrolled in a pilot randomized trial, comparing twice-weekly home-based strength exercise to wait list control. Participants conducted the exercises twice per week for 10 supervised weeks with 5 weeks of follow-up. Measures included DXA-measured lean mass, functional fitness assessments, blood biomarkers, and quality of life outcomes. RESULTS: On average, participants were 60.9 years old (SD = 8.7) with BMI of 39.9 kg/m(2) (SD = 15.2). At baseline, participants had 51.2% (SD = 6.0) body fat, which was not different between groups. Improvements were seen in the 30-s chair sit to stand (d = .99), the 30-s arm curl (d = .91), and the 8-ft up-and-go test (d = .63). No changes were measured for HbA1c or C-reactive protein. No changes were observed for flexibility (chair sit and reach, back scratch tests), 6-min walk test, maximum handgrip test, anxiety, depression, fatigue, or self-efficacy for exercise. CONCLUSIONS: Home-based muscle-strengthening exercise led to favorable and clinically relevant improvements in 3 of 7 physical function assessments. Physical function, body composition, blood biomarkers, and patient-reported outcomes were feasible to measure. These fitness improvements were observed over a relatively short time frame of 10 weeks.

BACKGROUND: Differences in patient characteristics and decision-making preferences have been described between those who elect breast-conserving surgery (BCS), unilateral mastectomy (UM) or contralateral prophylactic mastectomy (CPM) for breast cancer. However, it is not known whether preferred and actual decision-making roles differ across these surgery types or whether surgery choice reflects a woman’s goals or achieves desired outcomes. METHODS: Women diagnosed with Stage 0-III, unilateral breast cancer across eight large medical centers responded to a mailed questionnaire regarding treatment decision-making goals, roles, and outcomes. These data were linked to electronic medical records. Differences were assessed using descriptive analyses and logistic regression. RESULTS: There were 750 study participants: 60.1% BCS, 17.9% UM, and 22.0% CPM. On multivariate analysis, reducing worry about recurrence was a more important goal for surgery in the CPM group than the others. Although women’s preferred role in the treatment decision did not differ by surgery, the CPM group was more likely to report taking a more-active-than-preferred role than the BCS group. On multivariate analysis that included receipt of additional surgery, post-treatment worry about both ipsilateral and contralateral recurrence was higher in the BCS group than the CPM group (both p

Since 2000, the National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network (CISNET) modeling teams have developed and applied microsimulation and statistical models of breast cancer. Here, we illustrate the use of collaborative breast cancer multilevel systems modeling in CISNET to demonstrate the flexibility of systems modeling to address important clinical and policy-relevant questions. Challenges and opportunities of future systems modeling are also summarized. The 6 CISNET breast cancer models embody the key features of systems modeling by incorporating numerous data sources and reflecting tumor, person, and health system factors that change over time and interact to affect the burden of breast cancer. Multidisciplinary modeling teams have explored alternative representations of breast cancer to reveal insights into breast cancer natural history, including the role of overdiagnosis and race differences in tumor characteristics. The models have been used to compare strategies for improving the balance of benefits and harms of breast cancer screening based on personal risk factors, including age, breast density, polygenic risk, and history of Down syndrome or a history of childhood cancer. The models have also provided evidence to support the delivery of care by simulating outcomes following clinical decisions about breast cancer treatment and estimating the relative impact of screening and treatment on the United States population. The insights provided by the CISNET breast cancer multilevel modeling efforts have informed policy and clinical guidelines. The 20 years of CISNET modeling experience has highlighted opportunities and challenges to expanding the impact of systems modeling. Moving forward, CISNET research will continue to use systems modeling to address cancer control issues, including modeling structural inequities affecting racial disparities in the burden of breast cancer. Future work will also leverage the lessons from team science, expand resource sharing, and foster the careers of early stage modeling scientists to ensure the sustainability of these efforts., Author summary Since 2000, our research teams have used computer models of breast cancer to address important clinical and policy-relevant questions as part of the National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network (CISNET). Our 6 CISNET breast cancer models embody the key features of systems modeling by incorporating numerous data sources and reflecting tumor, person, and health system factors that change over time and interact to represent the burden of breast cancer. We have used our models to investigate questions related to breast cancer biology, compare strategies to improve the balance of benefits and harms of screening mammography, and support insights into the delivery of care by modeling outcomes following clinical decisions about breast cancer treatment. Moving forward, our research will continue to use systems modeling to address issues related to reducing the burden of breast cancer including modeling structural inequities affecting racial disparities. Our future work will also leverage lessons from engaging multidisciplinary scientific teams, expand efforts to share modeling resources with other researchers, and foster the careers of early stage modeling scientists to ensure the sustainability of these efforts.

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 (

Background The coronavirus disease 2019 (COVID-19) pandemic led to a near-total cessation of mammography services in the United States in mid-March 2020. It is unclear if screening and diagnostic mammography volumes have recovered to prepandemic levels and whether use has varied by women’s characteristics. Methods We collected data on 461 083 screening mammograms and 112 207 diagnostic mammograms conducted during January 2019 through July 2020 at 62 radiology facilities in the Breast Cancer Surveillance Consortium. We compared monthly screening and diagnostic mammography volumes before and during the pandemic stratified by age, race and ethnicity, breast density, and family history of breast cancer. Results Screening and diagnostic mammography volumes in April 2020 were 1.1% (95% confidence interval [CI] = 0.5% to 2.4%) and 21.4% (95% CI = 18.7% to 24.4%) of the April 2019 prepandemic volumes, respectively, but by July 2020 had rebounded to 89.7% (95% CI = 79.6% to 101.1%) and 101.6% (95% CI = 93.8% to 110.1%) of the July 2019 prepandemic volumes, respectively. The year-to-date cumulative volume of screening and diagnostic mammograms performed through July 2020 was 66.2% (95% CI = 60.3% to 72.6%) and 79.9% (95% CI = 75.4% to 84.6%), respectively, of year-to-date volume through July 2019. Screening mammography rebound was similar across age groups and by family history of breast cancer. Monthly screening mammography volume in July 2020 for Black, White, Hispanic, and Asian women reached 96.7% (95% CI = 88.1% to 106.1%), 92.9% (95% CI = 82.9% to 104.0%), 72.7% (95% CI = 56.5% to 93.6%), and 51.3% (95% CI = 39.7% to 66.2%) of the July 2019 prepandemic volume, respectively. Conclusions Despite a strong overall rebound in mammography volume by July 2020, the rebound lagged among Asian and Hispanic women, and a substantial cumulative deficit in missed mammograms accumulated, which may have important health consequences.

Background: Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence. Methods: Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users. Findings: During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p Interpretation: If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.

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.

Background: Overweight/obesity and dense breasts are strong breast cancer risk factors whose prevalences vary by race/ethnicity. The breast cancer population attributable risk proportions (PARP) explained by these factors across racial/ethnic groups are unknown. Methods: We analyzed data collected from 3,786,802 mammography examinations (1,071,653 women) in the Breast Cancer Surveillance Consortium, associated with 21,253 invasive breast cancers during a median of 5.2 years follow-up. HRs for body mass index (BMI) and breast density, adjusted for age and registry were estimated using separate Cox regression models by race/ethnicity (White, Black, Hispanic, Asian) and menopausal status. HRs were combined with observed risk-factor proportions to calculate PARPs for shifting overweight/obese to normal BMI and shifting heterogeneously/extremely dense to scattered fibroglandular densities. Results: The prevalences and HRs for overweight/obesity and heterogeneously/extremely dense breasts varied across races/ethnicities and menopausal status. BMI PARPs were larger for postmenopausal versus premenopausal women (12.0%–28.3% vs. 1.0%–9.9%) and nearly double among postmenopausal Black women (28.3%) than other races/ethnicities (12.0%–15.4%). Breast density PARPs were larger for premenopausal versus postmenopausal women (23.9%–35.0% vs. 13.0%–16.7%) and lower among premenopausal Black women (23.9%) than other races/ethnicities (30.4%–35.0%). Postmenopausal density PARPs were similar across races/ethnicities (13.0%–16.7%). Conclusions: Overweight/obesity and dense breasts account for large proportions of breast cancers in White, Black, Hispanic, and Asian women despite large differences in risk-factor distributions. Impact: Risk prediction models should consider how race/ethnicity interacts with BMI and breast density. Efforts to reduce BMI could have a large impact on breast cancer risk reduction, particularly among postmenopausal Black women.

Background: Survival with metastatic breast cancer (MBC) is highly variable and only ˜16% survive 10 years from the primary cancer diagnosis. In addition to treatments, proposed contributors to increased survival include cancer subtype, distribution of metastases, diet, exercise, and use of complementary and alternative medicine (CAM). We aimed to characterize long-term survivors with MBC through a self-administered survey. Methods: Patient advocates and researchers collaborated on developing and administering an ongoing web-based questionnaire (outliers.cancer.wisc.edu). Participants were recruited to this IRB-approved project through fliers, social media, MBC conferences, and Susan Love's Army of Women, with a recruiting focus on long-term survivors. Women and men are eligible if they are age ≥18 years old and have MBC by self-report. Eligible participants were invited to complete a detailed 28-part survey in English. Preliminary analysis was conducted by descriptive comparison of survivors ≥ 10 years from primary diagnosis versus those < 10 years. Results: Between March 6 and June 17, 2018, a total of 475 women and 1 man self-reported as living with MBC consented and completed the survey. Participants represented 48 U.S. states (n=414), and other countries on 4 continents (n=54). Two thirds of respondents (315) reported using medical records in preparing responses. Age of respondents ranged from 32-83 years (median 55), and participants survived from 4 months to 50 years (median 8.7), from primary breast cancer diagnosis. A total of 206 had lived ≥10 y from primary diagnosis and 270 Characteristics of long-term survivors and non-long term survivors with MBC Survival from primary diagnosis Survival from primary diagnosisFactor≥10 y2 drinks/wk26%20%HR-HER2+6%9%Smoking history36%33%HR+HER2+24%22%Sedentary23%21%Triple negative4%4%CAM use20%20%Oligometastatic (1-3)*53%50%Sleep hours/d, mean7.77.6*Number/site of tumors at time of metastatic presentation As expected, longer-term survivors were older and were less likely to have been diagnosed at stage 4. Surprisingly, there were no major differences in prevalence of breast cancer subtypes, though triple-negative breast cancer was rare in both groups. Long-term survivors reported modestly more alcohol intake and lower BMI. The two groups were well matched for oligometastatic and bone-only disease, which have been previously associated with longer survival. Additionally, there were similar rates of prior smoking, CAM use, and sedentary behavior. Conclusion: Interim analysis of this ongoing survey of MBC survivors finds that many disease and behavioral characteristics are similar between long-term versus short term survivors. Additional factors such as treatments, diet, and supplements will reported. Other possible factors, including tumor genetics, treatments and immunologic factors will be evaluated separately. Citation Format: Burkard ME, Lemmon K, Gilbert AD, Zhang X, Trentham-Dietz A, Dahl E, Rocque G. Characteristics of long-term survivors with metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-15.

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

Objectives Incidence-based mortality quantifies the distribution of cancer deaths and life-years lost, according to age at detection. We investigated the temporal distribution of the disease burden, and the effect of starting and stopping ages and interval between screening mammography examinations, on incidence-based mortality. Methods Incidence-based mortality was estimated using an established breast cancer simulation model, adapted and validated to simulate breast cancer incidence, screening performance, and delivery of therapies in Canada. Ten strategies were examined, with varying starting age (40 or 50), stopping age (69 or 74), and interval (1, 2, 3 years), and “No Screening.” Life-years lost were computed as the difference between model predicted time of breast cancer death and that estimated from life tables. Results Without screening, 70% of the burden in terms of breast cancer deaths extends between ages 45 and 75. The mean of the distribution of ages of detection of breast cancers that will be fatal in an unscreened population is 61.8 years, while the mean age of detection weighted by the number of life-years lost is 55, a downward shift of 6.8 years. Similarly, the mean age of detection for the distribution of life-years gained through screening is lower than that for breast cancer deaths averted. Conclusion Incidence-based mortality predictions from modeling elucidate the age dependence of the breast cancer burden and can provide guidance for optimizing the timing of screening regimens to achieve maximal impact. Of the regimens studied, the greatest lifesaving effect was achieved with annual screening beginning at age 40.

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.

Numerous laboratory and epidemiologic studies strongly implicate endogenous and exogenous estrogens in the etiology of breast cancer. Data summarized herein suggest that the ACI rat model of 17β-estradiol (E2)-induced mammary cancer is unique among rodent models in the extent to which it faithfully reflects the etiology and biology of luminal types of breast cancer, which together constitute ~70% of all breast cancers. E2 drives cancer development in this model through mechanisms that are largely dependent upon estrogen receptors and require progesterone and its receptors. Moreover, mammary cancer development appears to be associated with generation of oxidative stress and can be modified by multiple dietary factors, several of which may attenuate the actions of reactive oxygen species. Studies of susceptible ACI rats and resistant COP or BN rats provide novel insights into the genetic bases of susceptibility and the biological processes regulated by genetic determinants of susceptibility. This review summarizes research progress resulting from use of these physiologically relevant rat models to advance understanding of breast cancer etiology and prevention.

Background: Patients who receive an abnormal cancer screening result require follow-up for diagnostic testing, but the time to follow-up varies across patients and practices. Methods: We used a simulation study to estimate the change in lifetime screening benefits when time to follow-up for breast, cervical, and colorectal cancers was increased. Estimates were based on four independently developed microsimulation models that each simulated the life course of adults eligible for breast (women ages 50–74 years), cervical (women ages 21–65 years), or colorectal (adults ages 50–75 years) cancer screening. We assumed screening based on biennial mammography for breast cancer, triennial Papanicolaou testing for cervical cancer, and annual fecal immunochemical testing for colorectal cancer. For each cancer type, we simulated diagnostic testing immediately and at 3, 6, and 12 months after an abnormal screening exam. Results: We found declines in screening benefit with longer times to diagnostic testing, particularly for breast cancer screening. Compared to immediate diagnostic testing, testing at 3 months resulted in reduced screening benefit, with fewer undiscounted life years gained per 1,000 screened (breast: 17.3%, cervical: 0.8%, colorectal: 2.0% and 2.7%, from two colorectal cancer models), fewer cancers prevented (cervical: 1.4% fewer, colorectal: 0.5% and 1.7% fewer, respectively), and, for breast and colorectal cancer, a less favorable stage distribution. Conclusions: Longer times to diagnostic testing after an abnormal screening test can decrease screening effectiveness, but the impact varies substantially by cancer type. Impact: Understanding the impact of time to diagnostic testing on screening effectiveness can help inform quality improvement efforts. Cancer Epidemiol Biomarkers Prev; 27(2); 158–64. ©2017 AACR.

Breast cancer risk is intimately intertwined with exposure to estrogens. While more than 160 breast cancer risk loci have been identified in humans, genetic interactions with estrogen exposure remain to be established. Strains of rodents exhibit striking differences in their responses to endogenous ovarian estrogens (primarily 17β-estradiol). Similar genetic variation has been observed for synthetic estrogen agonists (ethinyl estradiol) and environmental chemicals that mimic the actions of estrogens (xenoestrogens). This review of literature highlights the extent of variation in responses to estrogens among strains of rodents and compiles the genetic loci underlying pathogenic effects of excessive estrogen signaling. Genetic linkage studies have identified a total of the 35 quantitative trait loci (QTL) affecting responses to 17β-estradiol or diethylstilbestrol in five different tissues. However, the QTL appear to act in a tissue-specific manner with 9 QTL affecting the incidence or latency of mammary tumors induced by 17β-estradiol or diethylstilbestrol. Mammary gland development during puberty is also exquisitely sensitive to the actions of endogenous estrogens. Analysis of mammary ductal growth and branching in 43 strains of inbred mice identified 20 QTL. Regions in the human genome orthologous to the mammary development QTL harbor loci associated with breast cancer risk or mammographic density. The data demonstrate extensive genetic variation in regulation of estrogen signaling in rodent mammary tissues that alters susceptibility to tumors. Genetic variants in these pathways may identify a subset of women who are especially sensitive to either endogenous estrogens or environmental xenoestrogens and render them at increased risk of breast cancer.

The Cancer Intervention and Surveillance Modeling Network (CISNET) Breast Cancer Working Group is a consortium of National Cancer Institute–sponsored investigators who use statistical and simulation modeling to evaluate the impact of cancer control interventions on long-term population-level breast cancer outcomes such as incidence and mortality and to determine the impact of different breast cancer control strategies. The CISNET breast cancer models have been continuously funded since 2000. The models have gone through several updates since their inception to reflect advances in the understanding of the molecular basis of breast cancer, changes in the prevalence of common risk factors, and improvements in therapy and early detection technology. This article provides an overview and history of the CISNET breast cancer models, provides an overview of the major changes in the model inputs over time, and presents examples for how CISNET breast cancer models have been used for policy evaluation.

Background. The UK Age trial compared annual mammography screening of women ages 40 to 49 years with no screening and found a statistically significant breast cancer mortality reduction at the 10-year follow-up but not at the 17-year follow-up. The objective of this study was to compare the observed Age trial results with the Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer model predicted results. Methods. Five established CISNET breast cancer models used data on population demographics, screening attendance, and mammography performance from the Age trial together with extant natural history parameters to project breast cancer incidence and mortality in the control and intervention arm of the trial. Results. The models closely reproduced the effect of annual screening from ages 40 to 49 years on breast cancer incidence. Restricted to breast cancer deaths originating from cancers diagnosed during the intervention phase, the models estimated an average 15% (range across models, 13% to 17%) breast cancer mortality reduction at the 10-year follow-up compared with 25% (95% CI, 3% to 42%) observed in the trial. At the 17-year follow-up, the models predicted 13% (range, 10% to 17%) reduction in breast cancer mortality compared with the non-significant 12% (95% CI, -4% to 26%) in the trial. Conclusions. The models underestimated the effect of screening on breast cancer mortality at the 10-year follow-up. Overall, the models captured the observed long-term effect of screening from age 40 to 49 years on breast cancer incidence and mortality in the UK Age trial, suggesting that the model structures, input parameters, and assumptions about breast cancer natural history are reasonable for estimating the impact of screening on mortality in this age group.

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.

As shared decision-making increasingly influences screening mammography, understanding similarities and differences between patients and physician perspectives becomes crucially important. This study compares women’s and physicians’ experiences of mammography shared decision making. Results reflect the critical gaps which exist between women’s expectations and physicians’ confidence in shared decision making regarding screening mammography.

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]

6562 Background: The COVID-19 pandemic has disrupted breast cancer control through short-term declines in screening, delays in diagnosis and reduced/delayed treatments. We projected the impact of COVID-19 on future breast cancer mortality.Methods: Three established Cancer Intervention and Surveillance Modeling Network (CISNET) models projected the impact of pandemic-related care disruptions on breast cancer mortality between 2020 and 2030 vs. pre-pandemic care patterns. Based on Breast Cancer Surveillance Consortium data, we modeled reductions in mammography screening utilization, delays in symptomatic cancer diagnosis, and reduced use of chemotherapy for women with early-stage disease for the first six months of the pandemic with return to pre-pandemic patterns after that time. Sensitivity analyses were performed to determine the effect of key model parameters, including the duration of the pandemic impact. Results: By 2030, the models project 1,297 (model range: 1,054-1,900) cumulative excess deaths related to reduced screening; 1,325 (range: 266-2,628) deaths from delayed diagnosis of symptomatic women, and 207 (range: 146-301) deaths from reduced chemotherapy use for early-stage cancer. Overall, the models predict 2,487 (range 1,713-4,875) excess deaths, representing a 0.56% (range: 0.36%-0.99%) cumulative increase over deaths that would be expected by 2030 in the absence of the pandemic’s disruptions. Sensitivity analyses indicated that the impact on mortality would approximately double if the disruptions lasted for a 12-month period. Conclusions: The impact of the initial pandemic-related disruptions in breast cancer care will have a small long-term cumulative impact on breast cancer mortality. The impact of the initial pandemic-related disruptions on breast cancer mortality will largely be mitigated by the rapid return to usual care. As the pandemic continues it will be important to monitor trends in care and reassess the mortality impact.[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.

Background: Approximately 35% of individuals with breast cancer meet guidelines for Germline genetic testing based on young age of onset, triple-negative subtype, and positive family history. While the national guidelines expanded opportunities for genetic testing, it is unclear how consistently these guidelines are being followed. It is also unclear which factors influence the decision to receive genetic testing or learn the results of testing. We present the results of a large multi-institution survey examining factors associated with the receipt of genetic testing, adherence to recommended guidelines for genetic testing and accessing results, in addition to evaluating correlates from the medical record compared to self-report. Methods: The Greater Plains Collaborative (GPC) Clinical Data Research Network (CDRN) Breast Cancer Group conducted a comprehensive multi-site (7 cancer care delivery sites across the Midwest) survey, Share Thoughts on Breast Cancer Study. Inclusion criteria were women >18 years, with microscopically-confirmed ductal carcinoma in situ or invasive (but not metastatic) breast cancer, diagnosed January 2013 to May 2014, and with no prior cancer other than breast cancer. Questionnaire data were linked to tumor registry data for those who consented to access their medical record. Results: 1235/1987 surveys were completed giving an overall response rate of 61.4%. Signed informed consent to utilize medical records was obtained for 852/1235 (69%). The median age of survivors at diagnosis was 59 years, 90.4% were white, 45.2% had a 4-year college degree or more, and 58.9% had private insurance. 486/1235 (39%) underwent genetic testing with 53 planning to in the future. 8% (39) reported having a deleterious mutation with 7% not knowing the results of their genetic testing. Among younger women with no family history of breast cancer, 74.8% of those under age 50 and 89.3% of those under age 45 reported receiving genetic testing. Of younger women with >1 relative with breast cancer, 86.7% (age $100,000 were tested vs. 27% of those with household income Conclusion: Our study demonstrates the feasibility of undertaking a comprehensive survey of breast cancer survivors from across the Midwest. Genetic testing rates of 39%, were consistent with national recommendations. However, there is still an opportunity to identify additional survivors who did not undergo testing within 2 years of their diagnosis, particularly those with lower education and poorly insured. There are ongoing efforts to determine why 7% of the cohort did not report knowing the results of their genetic testing. Citation Format: Blaes AH, McKay K, Riley D, Jatoi I, Rock J, Trentham-Dietz A, Chrischilles E, Klemp J. Factors associated with genetic testing in a cohort of breast cancer survivors [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-08-03.

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.

Re-excision surgeries for the treatment of ductal carcinoma in situ (DCIS) put a strain on patients and healthcare resources; however, intraoperative pathologic assessment of DCIS may lead to a reduction in these additional surgeries. This study examined the relationship between intraoperative pathologic assessment and subsequent operations in patients with a diagnosis of DCIS. Surveillance, Epidemiology, and End Results—Medicare patients diagnosed with DCIS from 1999 to 2007 who initially underwent partial mastectomy, without axillary surgery, were included in this study. Use of intraoperative frozen section or touch preparation during the initial surgery was assessed. Multivariable logistic regression was used to describe the relationship between the use of intraoperative pathologic assessment and any subsequent mastectomy or partial mastectomy within 90 days of the initial partial mastectomy. Of 8259 DCIS patients, 3509 (43 %) required a second surgery, and intraoperative pathologic assessment was performed for 2186 (26 %). Intraoperative pathologic assessment had no statistically significant effect on whether or not a subsequent breast surgery occurred (adjusted odds ratio 1.07, 95 % confidence interval 0.95–1.21; p = 0.293). Patient residence in a rural area, tumor size ≥2 cm, and poorly differentiated tumor grade were associated with a greater likelihood of subsequent surgery, while age 80 years and older was associated with a lower likelihood of subsequent surgery. The use of intraoperative frozen section or touch preparation during partial mastectomy from 1999 to 2007 was not associated with a reduction in subsequent breast operations in women with DCIS. These results highlight the need to identify cost-effective tools and strategies to reduce the need for additional surgery in patients with DCIS.

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.

We examined factors associated with self-reported use of genetic testing among breast cancer survivors based on a 2015 cross-sectional survey at eight Midwestern sites. Genetic testing was reported in 39% of our 1235 study participants, with higher utilization among those aged

PURPOSE: Long-term disease-free survival patterns following surgical, radiation, and endocrine therapy treatments for ductal carcinoma in situ (DCIS) are not well characterized in general US practice. METHODS: We identified 1,252 women diagnosed with DCIS in Vermont during 1994–2012 using data from the Vermont Breast Cancer Surveillance System, a statewide registry of breast imaging and pathology records. Poisson regression and Cox regression with time-varying hazards were used to evaluate disease-free survival among self-selected treatment groups. RESULTS: With 7.8 years median follow-up, 192 cases experienced a second breast cancer diagnosis. For women treated with breast conserving surgery (BCS) alone, the annual rate of second events decreased from 3.1% (95% CI: 2.2–4.2%) during follow-up years 1–5 to 1.7% (95% CI: 0.7–3.5%) after 10 years. In contrast, the annual rate of second events among women treated with BCS plus adjuvant radiation therapy increased from 1.8% (95% CI: 1.1–2.6%) during years 1–5 to 2.8% (95% CI: 1.6–4.7%) after 10 years (P