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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.

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.

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.

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.

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

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 investigated the association of oral contraceptive (OC) use and reproductive factors with colorectal cancer risk in a large population-based case-control study. Cases were women ages 20 to 74 years, living in Wisconsin, with a new diagnosis of colon (n = 1,122) or rectal (n = 366) cancer. Control participants were randomly selected from population lists of similarly aged female Wisconsin residents (n = 4,297). Risk factor information was collected through structured telephone interviews. Compared with never users, OC users had an odds ratio (OR) of 0.89 [95% confidence interval (95% CI), 0.75-1.06] for colorectal cancer. OC use associations did not differ significantly between colon and rectal cancer sites; however, when compared with never users, recent OC users (

We evaluated associations between reproductive and lifestyle risk factors with breast cancer tumor marker status in a case-control study. Cases were premenopausal women living in Vietnam and China who were eligible for a clinical trial of oophorectomy and tamoxifen as treatment for breast cancer (n = 682). Controls were nonrelative hospital visitors, matched on age to the cases (n = 649). Immunohistochemical analysis was used to identify the presence of estrogen receptor (ER) and progesterone receptor and the overexpression of HER-2/neu oncogene. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression, adjusted for known confounders. Overall, 280 (61%) tumor samples were ER positive and 176 (38%) were ER negative. HER-2/neu overexpression was detected in 161 (35%) samples, whereas 286 (26%) samples were HER-2/neu negative. We observed an inverse trend between increasing parity and decreasing breast cancer risk (P = 0.002). Women ages ≥25 years at first birth had increased breast cancer risk compared with women ages

Background: Survivors of ductal carcinoma in situ (DCIS), an early stage breast cancer, tend to decrease physical activity, gain weight, and maintain alcohol use following treatment. However, the impact of these health behaviors on long-term quality of life (QoL) in DCIS survivors has not been investigated. Methods: We examined the association of post-diagnosis body mass index (BMI), physical activity and smoking with QoL among 1,448 DCIS survivors aged 20–74, who were diagnosed during 1995–2006 and enrolled in the population-based Wisconsin In Situ Cohort. Health behaviors and QoL were self-reported during biennial post- diagnosis interviews. Physical and mental QoL were measured using the validated SF-36 questionnaire (higher scores reflect more positive QoL). Generalized linear regression was used to establish QoL mean scores in cross-sectional analyses, with multivariable adjustment for age, comorbidity status, education, and income. Results: Women reported 3,444 QoL observations over an average 7.9 years of follow-up. Physical health summary scale measures of QoL were significantly higher among women with healthy BMI (46.5 for healthy weight versus 40.5 for obese, P = 0.02) and those who were physically active (45.9 for active women versus 42.6 for inactive, P = 0.03). Mental health summary scale scores were significantly higher among non-smokers (51.2 for non-smokers versus 47.1 for current smokers, P < 0.01). These associations were consistent over increasing time since treatment up to 15 years. Conclusion: Our preliminary analysis suggests that maintaining healthy behaviors following DCIS treatment is associated with improved long-term QoL. Longitudinal analysis using cross-lagged regression is underway to evaluate the temporal association between health behavior and QoL. Understanding factors that impact QoL in DCIS survivors may inform interventions aimed at preventing negative health behaviors and optimizing long term quality of life following a DCIS diagnosis. The following are the 17 highest-scoring abstracts of those submitted for presentation at the 40th Annual ASPO meeting held March 13–15, 2016, in Columbus, OH.

Smoking history is associated with increased risk of most cancers, including breast cancer. Given the persistent effects of tobacco carcinogens, smoking history may also influence breast cancer survival. The few previous studies assessing this association were hindered by limited numbers of outcomes. METHODS: We assessed pre-diagnosis tobacco smoking in relation to survival in 22,870 female residents of Wisconsin, Massachusetts, or New Hampshire who were diagnosed with incident, invasive breast cancer between 1988–2008 at ages 20–79. All women reported pre-diagnosis tobacco use, as well as other known and suspected breast cancer risk factors. Information on breast cancer staging was obtained from state cancer registries. Proportional hazards regression with baseline hazard stratified on state of residence and study phase was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cause-specific death according to current smoking (at the time of the breast cancer diagnosis) and long-term (>30 years) smoking (prior to the diagnosis) adjusting for age at diagnosis, stage of disease at diagnosis, family history of breast cancer, age at first birth, menopausal status, hormone therapy use, body mass index, alcohol consumption, education, and mammography. RESULTS: During a median follow-up of 11.3 years from diagnosis, 7,807 deaths occurred, including 3,483 attributed to breast cancer, 328 to lung cancer, 415 to respiratory disease, and 1,553 to cardiovascular disease. Compared to nonsmokers, the HR were 1.2 (1.1–1.3. P = trend = 0.0003) for current smokers and 1.2 (1.1–1.3, P trend = 0.01) for >30 years of smoking. Current smoking was also associated with increased mortality from lung cancer, HR = 14.5 (10.1–20.8), cardiovascular disease, HR = 2.2 (1.9–2.5), and respiratory disease HR = 6.3 (4.8–8.2). CONCLUSIONS: In this large population-based sample of breast cancer cases, current and long-term smokers at the time of diagnosis were 20% more likely to die from breast cancer than never smokers adjusting for breast cancer stage. The elevated mortality risk observed here for known smoking-related diseases adds confidence to the breast cancer findings.Smoking history is associated with increased risk of most cancers, including breast cancer. Given the persistent effects of tobacco carcinogens, smoking history may also influence breast cancer survival. The few previous studies assessing this association were hindered by limited numbers of outcomes. METHODS: We assessed pre-diagnosis tobacco smoking in relation to survival in 22,870 female residents of Wisconsin, Massachusetts, or New Hampshire who were diagnosed with incident, invasive breast cancer between 1988–2008 at ages 20–79. All women reported pre-diagnosis tobacco use, as well as other known and suspected breast cancer risk factors. Information on breast cancer staging was obtained from state cancer registries. Proportional hazards regression with baseline hazard stratified on state of residence and study phase was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cause-specific death according to current smoking (at the time of the breast cancer diagnosis) and long-term (>30 years) smoking (prior to the diagnosis) adjusting for age at diagnosis, stage of disease at diagnosis, family history of breast cancer, age at first birth, menopausal status, hormone therapy use, body mass index, alcohol consumption, education, and mammography. RESULTS: During a median follow-up of 11.3 years from diagnosis, 7,807 deaths occurred, including 3,483 attributed to breast cancer, 328 to lung cancer, 415 to respiratory disease, and 1,553 to cardiovascular disease. Compared to nonsmokers, the HR were 1.2 (1.1–1.3. P = trend = 0.0003) for current smokers and 1.2 (1.1–1.3, P trend = 0.01) for >30 years of smoking. Current smoking was also associated with increased mortality from lung cancer, HR = 14.5 (10.1–20.8), cardiovascular disease, HR = 2.2 (1.9–2.5), and respiratory disease HR = 6.3 (4.8–8.2). CONCLUSIONS: In this large population-based sample of breast cancer cases, current and long-term smokers at the time of diagnosis were 20% more likely to die from breast cancer than never smokers adjusting for breast cancer stage. The elevated mortality risk observed here for known smoking-related diseases adds confidence to the breast cancer findings.Smoking history is associated with increased risk of most cancers, including breast cancer. Given the persistent effects of tobacco carcinogens, smoking history may also influence breast cancer survival. The few previous studies assessing this association were hindered by limited numbers of outcomes. METHODS: We assessed pre-diagnosis tobacco smoking in relation to survival in 22,870 female residents of Wisconsin, Massachusetts, or New Hampshire who were diagnosed with incident, invasive breast cancer between 1988–2008 at ages 20–79. All women reported pre-diagnosis tobacco use, as well as other known and suspected breast cancer risk factors. Information on breast cancer staging was obtained from state cancer registries. Proportional hazards regression with baseline hazard stratified on state of residence and study phase was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cause-specific death according to current smoking (at the time of the breast cancer diagnosis) and long-term (>30 years) smoking (prior to the diagnosis) adjusting for age at diagnosis, stage of disease at diagnosis, family history of breast cancer, age at first birth, menopausal status, hormone therapy use, body mass index, alcohol consumption, education, and mammography. RESULTS: During a median follow-up of 11.3 years from diagnosis, 7,807 deaths occurred, including 3,483 attributed to breast cancer, 328 to lung cancer, 415 to respiratory disease, and 1,553 to cardiovascular disease. Compared to nonsmokers, the HR were 1.2 (1.1–1.3. P = trend = 0.0003) for current smokers and 1.2 (1.1–1.3, P trend = 0.01) for >30 years of smoking. Current smoking was also associated with increased mortality from lung cancer, HR = 14.5 (10.1–20.8), cardiovascular disease, HR = 2.2 (1.9–2.5), and respiratory disease HR = 6.3 (4.8–8.2). CONCLUSIONS: In this large population-based sample of breast cancer cases, current and long-term smokers at the time of diagnosis were 20% more likely to die from breast cancer than never smokers adjusting for breast cancer stage. The elevated mortality risk observed here for known smoking-related diseases adds confidence to the breast cancer findings.Smoking history is associated with increased risk of most cancers, including breast cancer. Given the persistent effects of tobacco carcinogens, smoking history may also influence breast cancer survival. The few previous studies assessing this association were hindered by limited numbers of outcomes. METHODS: We assessed pre-diagnosis tobacco smoking in relation to survival in 22,870 female residents of Wisconsin, Massachusetts, or New Hampshire who were diagnosed with incident, invasive breast cancer between 1988–2008 at ages 20–79. All women reported pre-diagnosis tobacco use, as well as other known and suspected breast cancer risk factors. Information on breast cancer staging was obtained from state cancer registries. Proportional hazards regression with baseline hazard stratified on state of residence and study phase was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cause-specific death according to current smoking (at the time of the breast cancer diagnosis) and long-term (>30 years) smoking (prior to the diagnosis) adjusting for age at diagnosis, stage of disease at diagnosis, family history of breast cancer, age at first birth, menopausal status, hormone therapy use, body mass index, alcohol consumption, education, and mammography. RESULTS: During a median follow-up of 11.3 years from diagnosis, 7,807 deaths occurred, including 3,483 attributed to breast cancer, 328 to lung cancer, 415 to respiratory disease, and 1,553 to cardiovascular disease. Compared to nonsmokers, the HR were 1.2 (1.1–1.3. P = trend = 0.0003) for current smokers and 1.2 (1.1–1.3, P trend = 0.01) for >30 years of smoking. Current smoking was also associated with increased mortality from lung cancer, HR = 14.5 (10.1–20.8), cardiovascular disease, HR = 2.2 (1.9–2.5), and respiratory disease HR = 6.3 (4.8–8.2). CONCLUSIONS: In this large population-based sample of breast cancer cases, current and long-term smokers at the time of diagnosis were 20% more likely to die from breast cancer than never smokers adjusting for breast cancer stage. The elevated mortality risk observed here for known smoking-related diseases adds confidence to the breast cancer findings. The following are the 16 highest scoring abstracts of those submitted for presentation at the 38th Annual ASPO meeting held March 9–11, 2014, in Arlington, VA.

Concerns have been raised, largely on the basis of laboratory studies, regarding exposure to phenols, particularly bisphenol-A (BPA), in relation to hormone-related cancers. BPA is present in plastic consumer products including canned food linings and #7 polycarbonate plastics. According to recent NHANES data, human exposure as measured in urine is widespread (about 93% of people aged >5) and more common in females than males (Calafat EHP 2008). Concern regarding BPA in relation to breast cancer risk is based on in vivo and in vitro studies that suggest BPA may have a role in estrogen metabolism and mammary gland development. We examined the cross-sectional association of circulating serum levels of 3 phenols with mammographic breast density - a strong marker for breast cancer risk. A total of 264 postmenopausal women ages 55–70 years with no history of postmenopausal hormone use were recruited from mammography clinics in Madison, Wisconsin. Subjects completed a questionnaire regarding known breast cancer risk factors and provided a blood sample that was analyzed for octylphenol, nonylphenol, and BPA. Percent breast density (mean 15.3%, range 0.4–71.2%) was measured from subjects' mammograms using a computer-assisted thresholding method (Cumulus software). Since phenol levels are higher in the urine than in the serum, as expected many women had undetectable levels of the phenols in their serum: 86.7% octylphenol, 58.7% nonylphenol, and 73.1% BPA. After adjusting for age and body mass index in analysis of variance models, women with detectable serum BPA levels above the median (>0.56 ng/mL; N = 35) had higher percent breast density than women with BPA levels below the median (0.01–0.56 ng/mL; N = 36) and women with no detectable BPA (N = 193) in their serum (17.8% vs. 13.3% vs 12.7%, respectively; P = 0.01). Breast density was not associated with serum levels of either octylphenol or nonylphenol (P = 0.77, P = 0.36, respectively). Given that this study suggests that higher levels of BPA were associated with a clinically-relevant 5% greater breast density, further investigation into the potential influence of BPA on breast cancer risk using human populations is warranted. Supported by DOD BC062649, Komen FAS0703857, and NIH R03 CA139548. This abstract is one of the 20 highest scoring abstracts of those submitted for presentation at the 36th Annual ASPO meeting held March 4–6, 2012, in Washington, DC.

Almost 20% of new diagnoses of breast cancer are ductal carcinoma in situ (DCIS). DCIS increases risk for invasive breast cancer, and new prognostic markers of disease-free survival are needed to complement the few that are known. Limited studies have investigated the prognostic value of the tumor microenvironment, which is increasingly recognized as potentially playing a key role in tumor invasion and progression. Collagen is the most abundant component of the stroma surrounding the breast ducts, and laboratory studies suggest that collagen alignment facilitates cancer cell invasion and migration. Here we examined whether collagen alignment patterns in human DCIS specimens correlate with known prognostic markers. We evaluated collagen fiber alignment in 235 Wisconsin women diagnosed with DCIS in 1997–2000 who participated in a clinicopathologic cohort study. Fiber alignment was evaluated from routine H&E tissue slides prepared at the time of diagnosis using second harmonic generation (SHG) microscopy, a label-free multiphoton laser scanning technique that selectively images collagen. Images were evaluated for the presence of collagen fibers arranged in a radial pattern (approximately 75- to 90-degree angles) with respect to the DCIS lesion/stroma boundary, a phenotype termed TACS (Tumor Associated Collagen Signature). Chi-square tests were used to compare presence or absence of TACS with prognostic factors from a central review of pathology reports and slides, and analysis of tissue for ER, PR, Ki-67, and HER2. Overall, slides for about half (49.8%) of DCIS cases showed the TACS phenotype. TACS was not associated with age of the cases (P = 0.29), size of the lesion (P = 0.76), grade (P = 0.61), or margin size (P = 0.77). However, results suggested that TACS was more common (63.1%) among DCIS cases detected symptomatically than by mammography (47.3%, P = 0.09). TACS was more common among cases that were ER-negative (P = 0.002), PR-negative (P = 0.02), Ki-67 positive (P = 0.06), and HER2-positive (P = 0.002). This study underscores the relevance of the tumor microenvironment, in particular the arrangement of the collagen fiber matrix. On-going analysis will examine disease-free survival among DCIS cases according to patterns of collagen fiber alignment. The following are the 16 highest scoring abstracts of those submitted for presentation at the 38th Annual ASPO meeting held March 9–11, 2014, in Arlington, VA.

Purpose: Certain tumor factors have been associated with increased likelihood of a second breast diagnosis after treatment for ductal carcinoma in situ (DCIS) breast cancer. However, little information exists on modifiable lifestyle factors that affect prognosis after DCIS and may be useful for survivors in reducing their risk of a second breast cancer event. Methods: We examined the longitudinal association between body mass index (BMI), physical activity, and alcohol intake and risk of a second breast diagnosis among 1,925 DCIS survivors first diagnosed in 1997–2006 and enrolled in the Wisconsin In Situ Cohort. Data were collected during biennial patient interviews and diagnosis information was validated via pathology report. BMI, physical activity, and alcohol intake were examined over time using Chi-square and ANOVA methods. Cox proportional hazards regression was used to estimate the risk of a second diagnosis after adjustment for patient, tumor, and treatment factors. Repeated measures were incorporated to make use of exposure measurements taken at each post-diagnosis interview. Results: Over an average of 6.6 years of follow-up, 162 second breast cancer diagnoses were reported. Significant trends of increasing BMI and decreasing physical activity were observed over time since diagnosis (p < 0.001). For all women, a significant linear trend of increasing risk of a second diagnosis was found over increasing categories of post-diagnosis alcohol intake (p-trend 0.02). Among women treated with ipsilateral mastectomy, a reduction in risk was suggested with increasing post-diagnosis physical activity (HR 0.67, 95% CI 0.45, 1.02 for each additional hour/week). Among postmenopausal women, higher categories of post-diagnosis BMI were associated with increasing risk, although these results were of borderline significance (p-trend 0.09). Conclusion: This study is the first to examine the association of physical activity and alcohol intake with second breast diagnoses in an exclusively DCIS population. Our results suggest that DCIS survivors may reduce their risk of a second diagnosis by engaging in physical activity and reducing their alcohol consumption. 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.

Humans are exposed to a large number of environmental chemicals which have estrogenic activity, raising concern regarding potential effects on breast tissue and breast cancer risk. Phthalates are commonly found in personal care products, such as shampoos, lotions, and shaving products, and are present in many consumer plastics, adhesives, detergents, and pharmaceuticals. Parabens are also found in personal care products, and are additionally used as antimicrobials in foods. In vitro studies have demonstrated that many phthalates and parabens can bind to the estrogen receptor and initiate estrogenic cellular pathways, and a recent case-control study found that urinary concentrations of mono-ethyl-phthalate were positively associated with breast cancer risk. We examined the cross-sectional association of circulating serum levels of phthalates and parabens with mammographic breast density (a marker for breast cancer risk). A total of 261 postmenopausal women (ages 55–70, with no history of postmenopausal hormone use) were recruited from mammography clinics in Madison, Wisconsin. Patients completed a questionnaire regarding known breast cancer risk factors and provided a blood sample that was analyzed for mono-ethyl-phthalate, mono-butyl-phthalate, mono-benzyl-phthalate, butyl paraben, and propyl paraben. Percent breast density was measured from patients' mammograms as a continuous variable using a computer-assisted thresholding method (Cumulus software). After adjusting for age and body mass index, mono-ethyl-phthalate was positively associated with percent breast density. Women with detectable mono-ethyl-phthalate levels (>0.4 ng/mL; N = 36) had higher percent breast density than women with no detectable mono-ethyl-phthalate ( N = 225) in their serum (16.8% vs. 12.8%; P = 0.03). Serum levels of mono-butyl-phthalate and mono-benzyl-phthalate were generally below the limits of detection. Serum levels of butyl-paraben and propyl-paraben were higher (detectable in 55% and 67% of patients, respectively), but neither was associated with breast density ( P > 0.20). These results suggest that further investigation into the potential influence of mono-ethly-phthalate (and its parent compound diethyl-phthalate) on breast tissue is warranted. This abstract is one of the 14 highest scoring abstracts of those submitted for presentation at the 35th Annual Meeting of the American Society of Preventive Oncology, held March 5–8, 2011 in Las Vegas, NV.

Significant progress has been achieved in the United States in improving survival rates following an invasive breast cancer diagnosis. Previous studies have shown, however, that women living in geographic areas with high poverty and low education levels experience poorer survival. However, nearly all of these studies have been restricted to use of community-level data (e.g. US Census) on socioeconomic status (SES), and thus have been limited in their ability to identify individual-level factors associated with the disparity in survival. We examined individual-level SES in relation to breast cancer survival in a population-based cohort of invasive breast cancer survivors, ages 20-69, diagnosed in Wisconsin during 1995-2003 (N = 5,865). Information on household income, household size, and education was obtained during telephone interviews conducted shortly after diagnosis. Vital status was determined through December 31, 2006, using automated searches of the National Death Index. A total of 676 deaths (461 from breast cancer) were observed during 41,751 person-years of follow-up. Compared to college graduates, women with no further education beyond high school were more likely to die from breast cancer (Hazard Ratio, HR: 1.39; 95% CI: 1.10, 1.76) and from all causes (HR 1.42; 95% CI: 1.17, 1.73) following their breast cancer diagnosis. Similarly, women with household income less than 2.5 times that of the poverty level were more likely to die from breast cancer (HR 1.46; 95% CI: 1.03, 2.08) and from all causes (HR 1.64; 95% CI: 1.20, 2.24) compared to women with household income at least 5 times the poverty level. Women with lower education and income levels were less likely to have had annual mammograms prior to diagnosis. There was little difference in stage at diagnosis according to education level, but women with low income levels were 2.7 (95% CI: 1.2, 6.2) times more likely than women with high income to be diagnosed with distant-stage breast cancer. Adjustment for these factors attenuated, but did not eliminate, the association between SES and survival after diagnosis. Thus, the disparities in breast cancer survival that exist according to individual-level SES cannot be fully explained by variation in mammography use and stage at diagnosis. This abstract is one of the 17 highest scoring abstracts of those submitted for presentation at the 34th Annual Meeting of the American Society of Preventive Oncology, to be held March 20-23, 2010 in Bethesda, MD.