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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 (

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.

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.

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

Black women tend to be diagnosed with breast cancer at a more advanced stage than whites and subsequently experience elevated breast cancer mortality. We sought to determine whether there are racial differences in tumor natural history that contribute to these disparities. We used the University of Wisconsin Breast Cancer Simulation Model, a validated member of the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network, to evaluate the contribution of racial differences in tumor natural history to observed disparities in breast cancer incidence. We fit eight natural history parameters in race-specific models by calibrating to the observed race- and stage-specific 1975-2000 U.S. incidence rates, while accounting for known racial variation in population structure, underlying risk of breast cancer, screening mammography utilization, and mortality from other causes. The best fit models indicated that a number of natural history parameters must vary between blacks and whites to reproduce the observed stage-specific incidence patterns. The mean of the tumor growth rate parameter was 63.6 % higher for blacks than whites (0.18, SE 0.04 vs. 0.11, SE 0.02). The fraction of tumors considered highly aggressive based on their tendency to metastasize at a small size was 2.2 times greater among blacks than whites (0.41, SE 0.009 vs. 0.019, SE 0.008). Based on our simulation model, breast tumors in blacks grow faster and are more likely to metastasize earlier than tumors in whites. These differences suggest that targeted prevention and detection strategies that go beyond equalizing access to mammography may be needed to eliminate breast cancer disparities.

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

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

Ductal carcinoma in situ (DCIS) of the breast represents 15–20 % of new breast cancer diagnoses in the US annually. However, long-term competing risks of mortality, as well as racial differences in outcomes among US women with DCIS, are unknown. Case data from the years 1978–2010 were obtained using SEER*Stat software available through the National Cancer Institute from the 2010 SEER registries. Included were all women aged 40 and over with newly diagnosed DCIS. There were 67,514 women in the analysis, including 54,518 white women and 6,113 black women. A total of 12,173 deaths were observed over 607,287 person-years of follow-up. The 20-year cumulative incidence of all-cause death among women with DCIS was 39.6 % (CI 38.9–40.3). The corresponding 20-year rates for breast cancer death and CVD death were 3.2 % (CI 3.0–3.4) and 13.2 % (CI 12.8–13.7), respectively. Black women with DCIS had a higher risk of death compared to white women, with these hazard ratios elevated throughout the entire study period. For example, between 1990 and 2010, black women had a higher risk of all-cause death (HR 3.06, CI 2.39–3.91), breast cancer death (HR 5.78, CI 3.16–10.57), and CVD death (HR 6.43, CI 3.61–11.45) compared to white women diagnosed between 50 and 59 years of age. The risk of all-cause and CVD death was greater than breast cancer death among women diagnosed with DCIS over 20 years. Black women had higher risks of dying from all-causes compared to white women. These differences persisted into the modern treatment era.

Diabetes severity may influence breast cancer treatment choices. We examined whether receipt of guideline-concordant breast cancer treatment varied with diabetes severity. Cancer registry data from seven states regarding 6,912 stage I–III breast cancers were supplemented by medical record abstraction and physician verification. We used logistic regression models to examine associations of diabetes severity with guideline-concordant locoregional treatment, adjuvant chemotherapy, and hormonal therapy adjusted for sociodemographics, comorbidity, and tumor characteristics. We defined guideline concordance using National Comprehensive Cancer Network guidelines, and diabetes and comorbidities using the Adult Comorbidity Evaluation-27 index. After adjustment, there was significant interaction of diabetes severity with age for locoregional treatment (p = 0.001), with many diabetic women under age 70 less frequently receiving guideline-concordant treatment than non-diabetic women. Among similarly aged women, guideline concordance was lower for women with mild diabetes in their late fifties through mid-sixties, and with moderate/severe diabetes in their late forties to early sixties. Among women in their mid-seventies to early eighties, moderate/severe diabetes was associated with increased guideline concordance. For adjuvant chemotherapy, moderate/severe diabetes was less frequently associated with guideline concordance than no diabetes [OR 0.58 (95 % CI 0.36–0.94)]. Diabetes was not associated with guideline-concordant hormonal treatment (p = 0.929). Some diabetic women were less likely to receive guideline-concordant treatment for stage I–III breast cancer than non-diabetic women. Diabetes severity was associated with lower guideline concordance for locoregional treatment among middle-aged women, and lower guideline concordance for adjuvant chemotherapy. Differences were not explained by comorbidity and may contribute to potentially worse breast cancer outcomes.

Randomized trials have demonstrated the efficacy of radiation and tamoxifen in reducing risk of second events after breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS), but the comparative effectiveness of mastectomy, BCS, and adjuvant treatments have not been established in community practice. We examined disease-free survival among 1,676 DCIS cases diagnosed during 1995–2006 in the population-based Wisconsin In Situ Cohort study. Information on patient and tumor characteristics, treatments, and second breast cancer events were collected via a comprehensive review of data from patient interviews, the statewide cancer registry, and pathology reports. Breast cancer disease-free survival was evaluated according to treatment while adjusting for patient and tumor characteristics. After an average of 7.1 years of follow-up, 143 second breast cancer events occurred. Overall five-year disease-free survival was similar among women treated with ipsilateral mastectomy (95.6%; 95% CI: 93.5, 97.0) compared to women treated with BCS and radiation (94.8%; 95% CI: 92.8, 96.1), though women receiving BCS without radiation experienced poorer overall disease-free survival (87.0%; 95% CI: 80.6, 91.5). Among women treated with BCS and radiation, the addition of tamoxifen was associated with a 30% (HR = 0.70; 95% CI: 0.41, 1.19) reduction in risk of second events. Women treated with BCS, radiation, and tamoxifen had comparable risk of a second event as those treated with ipsilateral mastectomy (HR=1.20; 95% CI: 0.71, 2.02). In this population-based sample, the use of BCS with radiation and tamoxifen resulted in high disease-free survival rates comparable to those achieved by ipsilateral mastectomy.

Laboratory studies have demonstrated that vitamin D has a number of chemopreventive properties, and that these properties may be mediated or modified by other molecules in the vitamin D pathway, such as parathyroid hormone (PTH) or calcium. However, there is little epidemiologic data exploring the effects of vitamin D on breast cancer risk in the context of these other molecules. We examined a panel of molecules in the vitamin D pathway in relation to mammographic breast density, a marker of breast cancer risk, in the Wisconsin Breast Density Study. A total of 238 postmenopausal women (ages 55–70, with no history of postmenopausal hormone use) were enrolled from mammography clinics in Madison, Wisconsin. Subjects provided blood samples that were analyzed for levels of 25-hydroxy vitamin D [25(OH)D], PTH, insulin-like growth factor-1 (IGF-1), IGF-binding protein 3 (IGFBP-3), retinol, and calcium. Percent breast density was measured using Cumulus software. In age-adjusted analyses there was a positive association between 25(OH)D and percent breast density (P = 0.05; mean percent density = 11.3% vs. 15.6% for 1st vs. 4th quartile of 25(OH)D). Breast density was inversely associated with PTH (P = 0.05; 16.0% vs. 11.4% for Q1 vs. Q4) and positively associated with the IGF-1:IGFBP-3 molar ratio (P = 0.02; 11.9% vs. 15.6% for Q1 vs. Q4). However, these associations were all null after further adjustment for body mass index (BMI; P > 0.25). The independent relation between 25(OH)D and breast density remained null among subgroups defined by BMI and serum levels of retinol, calcium, and estradiol. These results suggest no strong independent associations between the circulating molecules of the vitamin D pathway and mammographic breast density in postmenopausal women. While it remains possible that vitamin D could influence breast cancer risk, our results suggest that such an effect would be mediated through pathways other than breast density.

Women with ductal carcinoma in situ (DCIS) of the breast represent a growing cancer survivor population with a diagnosis of uncertain malignant potential. These survivors face an absence of scientific guidelines regarding lifestyle changes that can help to prevent a breast cancer recurrence. In this first report from the Wisconsin In Situ Cohort (WISC) study, we examine how women are currently changing their lifestyle behaviors and medication use following a diagnosis of DCIS. At study entry (1997–2006), 1,959 subjects (78% of eligible) with DCIS were identified from the Wisconsin cancer registry and administered an interview assessing behaviors prior to diagnosis. Follow-up interviews were completed every 2 years after the initial interview, beginning in 2003 and continuing through 2006. After adjusting for age and calendar year, women were 2.2 kg (95% CI 1.4, 3.0) heavier, 35% (95% CI 20, 47) less likely to be a smoker, 19% (95% CI −1, 43) more likely to use non-steroidal anti-inflammatory drugs, and 57% (95% CI 26, 95) more likely to use antidepressants after a DCIS diagnosis compared to 1 year prior to diagnosis. Use of postmenopausal hormones decreased sharply (OR = 0.06; 95% CI 0.04, 0.09) following a DCIS diagnosis. These findings indicate that women make substantial changes in their behaviors after a DCIS diagnosis. This cohort will be further monitored to evaluate the association between these behaviors and health outcomes following DCIS.

Breast cancer incidence in the United States has declined dramatically since the year 2002. To improve our understanding of the underlying factors driving breast cancer trends, we explored potential socioeconomic disparities in the recent decline in incidence. We examined the decline in breast cancer incidence according to county-level socioeconomic indicators using data from the Surveillance, Epidemiology and End Results (SEER) program. Since socioeconomic status is associated with mammography screening, we also examined the relation between incidence of ductal carcinoma in situ (DCIS; a strong marker of mammography utilization) and the decline in invasive breast cancer. The reduction in invasive breast cancer incidence between 1998-2001 and 2003-2006 in the SEER 9 registries was greatest among women living in counties with higher median household income (-16% change foror = $85,000 vs. -4% for$35,000; P(trend)0.01) and a higher percentage of adults aged 25 years or older with a bachelor's degree (-13% change foror = 40% vs. -8% for15%; P(trend)0.01). Counties with higher DCIS incidence during 1985-2001 had a larger decrease in invasive breast cancer incidence (absolute decrease 1.7 percentage points greater per 5 per 100,000 increase in DCIS incidence; P = 0.01). This association was present for both ER-positive and ER-negative invasive cancers (P0.05). In summary, the decline in breast cancer incidence has been largest in areas with high socioeconomic status and high screening utilization rates. These results are consistent with the hypothesis that a saturation of screening mammography utilization contributed to the overall decline in breast cancer incidence.

To examine the association between breast cancer risk factors and second primary cancers (independent diagnoses occurring at least 12 months after the initial breast cancer diagnosis) among breast cancer survivors. In this population-based study, cancer outcomes among breast cancer survivors first diagnosed during 1987–2000 were investigated. Invasive breast cancer cases were identified from the statewide tumor registry and interviewed regarding their pre-diagnosis risk factors, including reproductive and lifestyle characteristics, approximately 1 year after diagnosis. Data on second primary cancers (not recurrences) and deaths were obtained by linkage with tumor registry reports and death certificates through December 31, 2002. Hazard ratios (HR) were estimated using proportional hazards regression stratified by age and adjusted for stage and other factors. Among the 10,953 breast cancer cases, 10.8% experienced a second cancer diagnosis within an average of 7 years (including 488 breast, 132 colorectal, 113 endometrial, and 36 ovarian cancers). Risk of a second primary breast cancer increased according to low parity (P = 0.002), older age at menopause (P = 0.08), greater body mass index (P = 0.003) and adult weight gain (P = 0.02), and a family history of breast cancer-particularly among women with 2 or more first-degree affected relatives (HR = 1.8, 95% CI: 1.1–2.9). Reduced risk of colorectal cancer after breast cancer was observed in relation to older ages at menarche (P = 0.05), younger age at menopause (P = 0.04), postmenopausal hormone use (HR = 0.4, 95% CI: 0.3–0.7), normal body mass index (P = 0.07), and infrequent alcohol consumption (P = 0.01). Second endometrial cancer risk was associated with increasing body mass index (P