US Breast Research Articles

Modeling Breast Cancer Incidence Rates: A Comparison between the Components of Functional Time Series (FTS) Model Applied on Karachi (Pakistan) and US Data

Several studies showed that the breast cancer incidence rates are higher in high-income (developed) countries, due to the link of breast cancer with several risk factors and the presence of systematic screening policies. Some of the authors suggest that lower breast cancer incidence rates in low-income (developing) countries probably reflect international variation in hormonal factors and accessibility to early detection facilities. Recent studies showed that the breast cancer increased rapidly among women in Pakistan (a developing country) and it became the first malignancy among females of Pakistan. Although, the incidence rates may contain important evidence for understanding and control of the disease; however in Pakistan, the breast cancer incidence data have never been available in the last five decades since independence; rather, only hospital-based data are available. In this study, we intend to apply Functional Time Series (FTS) models to the breast cancer incidence rates of United State (developed country), and to see the difference between various components (age and time) of Functional Time Series (FTS) models applied independently on the breast cancer incidence rates of Karachi (Pakistan) and US. Past studies have already suggested that the incidence of US breast cancer cases was expected to increase in the coming decades. A progressive increase in the number of new cases is already predetermined by the high birth rate that occurred during the middle part of the century, and it will lead to nearly a doubling in the number of cases in about 4 decades. We also obtain 15 years predictions of breast cancer incidence rates in United States and compare them with the forecasts of incidence curves for Karachi. Development of methods for cancer incidence trend forecasting can provide a sound and accurate foundation for planning a comprehensive national strategy for optimal partitioning of research resources between the need for development of new treatments and the need for new research directed toward primary preventive measures.

Medical malpractice concerns and defensive medicine: a nationwide survey of breast pathologists.

"Assurance behaviors" in medical practice involve providing additional services of marginal or no medical value to avoid adverse outcomes, deter patients from filing malpractice claims, or ensure that legal standards of care were met. The extent to which concerns about medical malpractice influence assurance behaviors of pathologists interpreting breast specimens is unknown. Breast pathologists (n = 252) enrolled in a nationwide study completed an online survey of attitudes regarding malpractice and perceived alterations in interpretive behavior due to concerns of malpractice. Associations between pathologist characteristics and the impact of malpractice concerns on personal and colleagues' assurance behaviors were determined by χ(2) and logistic regression analysis. Most participants reported using one or more assurance behaviors due to concerns about medical malpractice for both their personal (88%) and colleagues' (88%) practices, including ordering additional stains, recommending additional surgical sampling, obtaining second reviews, or choosing the more severe diagnosis for borderline cases. Nervousness over breast pathology was positively associated with assurance behavior and remained statistically significant in a multivariable logistic regression model (odds ratio, 2.5; 95% confidence interval, 1.0-6.1; P = .043). Practicing US breast pathologists report exercising defensive medicine by using assurance behaviors due to malpractice concerns.

“I wish I'd known”: patients' suggestions for supporting sexual quality of life after diagnosis with metastatic breast cancer

ABSTRACTResearch has found that breast cancer and its treatments can have severe consequences for patients' sexual quality of life (SQoL); however, patients often report not knowing about possible impacts of treatment on their sexual well-being. This gap in information provision has been especially prominent for those diagnosed with metastatic breast cancer (MBC). To address the development of resources for patients diagnosed with MBC, the current study examined patients' descriptions of resources needed to support their SQoL in palliative care. Semi-structured interviews were conducted with 32 women diagnosed with MBC, aged 35--77 in a US breast cancer practice. Patients were asked to describe those issues that were most pressing and the supports they would find most valuable to improving their SQoL. Thematic analysis focused on what was missing in their care and what they wished they knew (or wish they had been told) about cancer and their SQoL. Four themes were developed from the interviews: (1) unexpected embodied loss and mourning; (2) silences; (3) desires for others' expertise, and (4) worries about normalcy. Findings across these themes highlighted how patients' psychosexual needs included both pressing instrumental needs as well as desires for support from oncological medical providers concerning the subjective experience of breast cancer.

Improvements in US Breast Cancer Survival and Proportion Explained by Tumor Size and Estrogen-Receptor Status.

Breast cancer mortality began declining in many Western countries during the late 1980s. We estimated the proportion of improvements in stage- and age-specific breast cancer survival in the United States explained by tumor size or estrogen receptor (ER) status. We estimated hazard ratios for breast cancer-specific death from time of invasive breast cancer diagnosis in the National Cancer Institute's Surveillance, Epidemiology, and End Results 9 Registries Database from 1973 to 2010, with and without stratification by tumor size and ER status. Hazards from breast cancer-specific death declined from 1973 to 2010, not only in the first 5 years after diagnosis, but also thereafter. Stratification by tumor size explained less than 17% of the improvements comparing 2005 to 2010 versus 1973 to 1979, except for women age ≥ 70 years with local (49%) or regional (38%) disease. Tumor size usually accounted for more of the improvement in the first 5 years after diagnosis than later. Additional adjustment for ER status (positive, negative, or unknown) from 1990 to 2010 did not explain much more of the improvement, except for women age ≥ 70 years within 5 years after diagnosis. Most stage-specific survival improvement in women younger than age 70 years old is unexplained by tumor size and ER status, suggesting a key role for treatment. In the first 5 years after diagnosis, tumor size contributed importantly for women ≥ 70 years old with local and regional stage, and stratification by tumor size and ER status explained even more of the survival improvement among women age ≥ 70 years.

Paths to health equity: Local area variation in progress toward eliminating breast cancer mortality disparities, 1990-2009.

US breast cancer deaths have been declining since 1989, but African American women are still more likely than white women to die of breast cancer. Black/white disparities in breast cancer mortality rate ratios have actually been increasing. Across 762 US counties with enough deaths to generate reliable rates, county-level, age-adjusted breast cancer mortality rates were examined for women who were 35 to 74 years old during the period of 1989-2010. Twenty-two years of mortality data generated twenty 3-year rolling average data points, each centered on a specific year from 1990 to 2009. Mixed linear models were used to group each county into 1 of 4 mutually exclusive trend patterns. The most recent 3-year average black breast cancer mortality rate for each county was also categorized as being worse or not worse than the breast cancer mortality rate for the total US population. More than half of the counties (54%) showed persistent, unchanging disparities. Roughly 1 in 4 (24%) had a divergent pattern of worsening black/white disparities. However, 10.5% of the counties sustained racial equality over the 20-year period, and 11.7% of the counties actually showed a converging pattern from high disparities to greater equality. Twenty-three counties had 2008-2010 black mortality rates better than the US average mortality rate. Disparities are not inevitable. Four US counties have sustained both optimal and equitable black outcomes as measured by both absolute (better than the US average) and relative benchmarks (equality in the local black/white rate ratio) for decades, and 6 counties have shown a path from disparities to health equity.

Advanced Breast Imaging Availability by Screening Facility Characteristics

To determine the relationship between screening mammography facility characteristics and on-site availability of advanced breast imaging services required for supplemental screening and the diagnostic evaluation of abnormal screening findings. We analyzed data from all active imaging facilities across six regional registries of the National Cancer Institute-funded Breast Cancer Surveillance Consortium offering screening mammography in calendar years 2011-2012 (n = 105). We used generalized estimating equations regression models to identify associations between facility characteristics (eg, academic affiliation, practice type) and availability of on-site advanced breast imaging (eg, ultrasound [US], magnetic resonance imaging [MRI]) and image-guided biopsy services. Breast MRI was not available at any nonradiology or breast imaging-only facilities. A combination of breast US, breast MRI, and imaging-guided breast biopsy services was available at 76.0% of multispecialty breast centers compared to 22.2% of full diagnostic radiology practices (P = .0047) and 75.0% of facilities with academic affiliations compared to 29.0% of those without academic affiliations (P = .04). Both supplemental screening breast US and screening breast MRI were available at 28.0% of multispecialty breast centers compared to 4.7% of full diagnostic radiology practices (P < .01) and 25.0% of academic facilities compared to 8.5% of nonacademic facilities (P = .02). Screening facility characteristics are strongly associated with the availability of on-site advanced breast imaging and image-guided biopsy service. Therefore, the type of imaging facility a woman attends for screening may have important implications on her timely access to supplemental screening and diagnostic breast imaging services.

US breast cancer mortality trends in young women according to race.

Young age at diagnosis has a negative prognostic impact on outcome in patients with breast cancer (BC). In the current study, the authors sought to determine whether there is a differential effect of race and examined mortality trends according to race and age. The Surveillance, Epidemiology, and End Results program was used to identify women aged <50 years with invasive BC diagnosed between 1990 and 2009. Multivariate regression analyses were performed to determine the risk-adjusted likelihood of survival for white and black patients. Annual hazards of BC death according to race and calendar period and adjusted relative hazards of death for white and black women stratified by age were computed. A total of 162,976 women were identified, 126,573 of whom were white, 20,405 of whom were black, and 15,998 of whom were of other races. At a median follow-up of 85 months, the 5-year disease specific survival rates were 90.1% for white patients and 79.3% for black patients. Annual hazards of death in white patients decreased by 26% at 5 years after diagnosis in contrast to the hazards in black patients, which decreased by only 19%. With 1990 as the referent year, the adjusted relative hazards of death in women aged <40 years in 2005 were 0.55 (95% confidence interval [95% CI], 0.46-0.66) and 0.68 (95% CI, 0.49-0.93), respectively, for white and black women. In women aged 40 to 49 years, adjusted hazards of death were 0.53 (95% CI, 0.47-0.60) and 0.78 (95% CI, 0.61-0.99), respectively, for white and black women. Among young women diagnosed with BC, black patients have a worse outcome compared with white patients. Mortality declines have been observed over time in both groups, although more rapid gains have been reported to occur in white women. Emphasis should be placed on improving outcomes for young patients with BC.

Adoption of Hypofractionated Radiation Therapy for Breast Cancer After Publication of Randomized Trials

Large randomized trials have established the noninferiority of shorter courses of "hypofractionated" radiation therapy (RT) to the whole breast compared to conventional courses using smaller daily doses in the adjuvant treatment of selected breast cancer patients undergoing lumpectomy. Hypofractionation is more convenient and less costly. Therefore, we sought to determine uptake of hypofractionated breast RT over time. In the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database, we identified 16,096 women with node-negative breast cancer and 4269 with ductal carcinoma in situ (DCIS) who received lumpectomy followed by more than 12 fractions of RT between 2004 and 2010. Based on Medicare claims, we determined the number of RT treatments given and grouped patients into those receiving hypofractionation (13-24) or those receiving conventional fractionation (≥25). We also determined RT technique (intensity modulated RT or not) using Medicare claims. We evaluated patterns and correlates of hypofractionation receipt using bivariate and multivariable analyses. Hypofractionation use was similar in patients with DCIS and those with invasive disease. Overall, the use of hypofractionation increased from 3.8% in 2006 to 5.4% in 2007, to 9.4% in 2008, and to 13.6% in 2009 and 2010. Multivariable analysis showed increased use of hypofractionation in recent years and in patients with older age, smaller tumors, increased comorbidity, higher regional education, and Western SEER regions. However, even in patients over the age of 80, the hypofractionation rate in 2009 to 2010 was only 25%. Use of intensity modulated RT (IMRT) also increased over time (from 9.4% in 2004 to 22.7% in 2009-2010) and did not vary significantly between patients receiving hypofractionation and those receiving traditional fractionation. Hypofractionation use increased among low-risk older US breast cancer patients with publication and maturation of evidence from randomized trials, but overall use of this cost-saving approach remained low. This contrasts with the more rapid rate of adoption of IMRT in the same time period, a costly innovation supported by less strong evidence of benefit.

Effects of Screening and Systemic Adjuvant Therapy on ER-Specific US Breast Cancer Mortality

Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker. We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy. In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13-21) and 5 per 100000 women (model range = 3-6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%-87.8% vs 85.7%-96.5%). As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms.

Diminishing Relative Contraindications for Immediate Breast Reconstruction: A Multicenter Study

During the past decade, there has been a rise in US breast reconstruction rates, with a greater expansion in prosthetic-based techniques relative to autologous transfer. Immediate reconstruction in high-risk oncologic and surgical patients might be a contributing factor to these trends. The National Cancer Data Base from the American College of Surgeons and the American Cancer Society was used to identify a breast cancer cohort (1998 to 2011) treated with mastectomy. The patients were divided into high risk and low risk based on presence or absence of historic surgical or oncologic relative contraindications. Reconstructions were categorized as either autologous or implants. To understand trends for each high-risk characteristic, rates were adjusted by 1,000 total mastectomies performed for patients within each specific group and analyzed with Poisson regression. Information from 1,040,088 patients with mastectomy was included. Rates of high-risk features did not change from 1998 to 2011. The increase in immediate reconstruction rates was greater for high-risk than low-risk patients (incidence rate ratio = 1.09 vs 1.06; p < 0.05 for both). There was a greater rate increase in implant than autologous reconstructions for both high-risk and low-risk groups. For high-risk patients, implant use increased for all features, but with the greatest change for elderly, comorbidities, and post-mastectomy radiotherapy (p < 0.01). For high-risk patients, autologous tissue use increased significantly for all features except pre-mastectomy radiotherapy. Breast reconstruction increased in high-risk surgical and oncologic patients, suggestive of a diminishing set of relative contraindications. Increased implant use in high-risk patients might be a contributing factor toward the preferential national expansion of prosthetic techniques.

Increasing Value by Increasing Volume: Call for Changes in US Breast Cancer Screening Practices

Increasing Value by Increasing Volume: Call for Changes in US Breast Cancer Screening Practices

Association of Fatigue with Perceived Stress in Chinese Women with Early Stage Breast Cancer Awaiting Adjuvant Radiotherapy.

Cancer-related fatigue (CRF) is common in women with breast cancer, but little is known of its relationship with perceived stress. We conducted a cross-sectional study to explore the associations of CRF with perceived stress, anxiety, depression, pain and sleep quality in 133 Chinese women (aged 25-68 years) with early stage breast cancer. The majority of women had completed surgery and chemotherapy and were awaiting radiotherapy. Self-administered questionnaires consisting of the Brief Fatigue Inventory, Perceived Stress Scale-10, Hospital Anxiety and Depression Scale, Brief Pain Inventory, and Pittsburgh Sleep Quality Index were used to collect data. Forty-five per cent of the women were severely fatigued. Compared with local healthy women and US breast cancer patients, the group's mean perceived stress score was significantly higher (both p < 0.01). Higher perceived stress (β = 0.18, p = 0.032), higher anxiety (β = 0.30, p < 0.001) and higher pain severity (β = 0.38, p < 0.001) were associated with increased severity of CRF. The association of CRF with perceived stress was partially mediated by anxiety, suggesting a possible pathway from cancer and cancer treatment to CRF via stress appraisals and emotional distress. The findings indicate the importance of monitoring the psychological status of patients during treatment.

Mammography utilization among Black and White Medicare beneficiaries in high breast cancer mortality US counties

Disparities in US breast cancer mortality between older Black and White women have increased in the last 20 years. Regular mammography use is important for early detection and treatment: its utilization among older Blacks especially in counties with high Black mortality is of interest, but its extent and determinants are unknown. We used Medicare claims for Black and White women 65–74 years old in 203 counties with the highest Black breast cancer mortality. Outcomes over 6 years were as follows: ever mammogram, i.e., C 1 screening mammogram, and regular mammogram, i.e., C 3 mammograms. With logistic regressions, we examined the independent effect of race on screening controlling for individual- and county-level factors. Of 406,602 beneficiaries, 17 % were Black. Ever and regular mammogram was significantly lower among Blacks (51.6 vs. 56.9 %; 32.9 vs. 43.1 %, respectively). Controlling for covariates, including use of cervical cancer screening, flu shots, or lipids tests, Black women were more likely to have ever mammogram (OR 1.23, CI 1.20–1.25), but not regular mammogram (OR 0.95, CI 0.93–0.97) than White women. County-level managed care penetration was negatively associated with ever and regular mammograms. In Medicare enrollees from these counties, breast cancer screening was low. Black women had same or better odds of screening than White women. Some health care factors, e.g., managed care, were negatively associated with screening. Further studies on the determinants of mammography utilization in older women from these counties are warranted.

The California Breast Cancer Survivorship Consortium (CBCSC): prognostic factors associated with racial/ethnic differences in breast cancer survival.

Racial/ethnic disparities in mortality among US breast cancer patients are well documented. Our knowledge of the contribution of lifestyle factors to disease prognosis is based primarily on non-Latina Whites and is limited for Latina, African American, and Asian American women. To address this knowledge gap, the California Breast Cancer Survivorship Consortium (CBCSC) harmonized and pooled interview information (e.g., demographics, family history of breast cancer, parity, smoking, alcohol consumption) from six California-based breast cancer studies and assembled corresponding cancer registry data (clinical characteristics, mortality), resulting in 12,210 patients (6,501 non-Latina Whites, 2,060 African Americans, 2,032 Latinas, 1,505 Asian Americans, 112 other race/ethnicity) diagnosed with primary invasive breast cancer between 1993 and 2007. In total, 3,047 deaths (1,570 breast cancer specific) were observed with a mean (SD) follow-up of 8.3 (3.5) years. Cox proportional hazards regression models were fit to data to estimate hazards ratios (HRs) and 95 % confidence intervals (CIs) for overall and breast cancer-specific mortality. Compared with non-Latina Whites, the HR of breast cancer-specific mortality was 1.13 (95 % CI 0.97-1.33) for African Americans, 0.84 (95 % CI 0.70-1.00) for Latinas, and 0.60 (95 % CI 0.37-0.97) for Asian Americans after adjustment for age, tumor characteristics, and select lifestyle factors. The CBCSC represents a large and racially/ethnically diverse cohort of breast cancer patients from California. This cohort will enable analyses to jointly consider a variety of clinical, lifestyle, and contextual factors in attempting to explain the long-standing disparities in breast cancer outcomes.

Which strategies reduce breast cancer mortality most?

BACKGROUNDUS breast cancer mortality is declining, but thousands of women still die each year.METHODSTwo established simulation models examine 6 strategies that include increased screening and/or treatment or elimination of obesity versus continuation of current patterns. The models use common national data on incidence and obesity prevalence, competing causes of death, mammography characteristics, treatment effects, and survival/cure. Parameters are modified based on obesity (defined as BMI ≥ 30 kg/m2). Outcomes are presented for the year 2025 among women aged 25+ and include numbers of cases, deaths, mammograms and false-positives; age-adjusted incidence and mortality; breast cancer mortality reduction and deaths averted; and probability of dying of breast cancer.RESULTSIf current patterns continue, the models project that there would be about 50,100-57,400 (range across models) annual breast cancer deaths in 2025. If 90% of women were screened annually from ages 40 to 54 and biennially from ages 55 to 99 (or death), then 5100-6100 fewer deaths would occur versus current patterns, but incidence, mammograms, and false-positives would increase. If all women received the indicated systemic treatment (with no screening change), then 11,400-14,500 more deaths would be averted versus current patterns, but increased toxicity could occur. If 100% received screening plus indicated therapy, there would be 18,100-20,400 fewer deaths. Eliminating obesity yields 3300-5700 fewer breast cancer deaths versus continuation of current obesity levels.CONCLUSIONSMaximal reductions in breast cancer deaths could be achieved through optimizing treatment use, followed by increasing screening use and obesity prevention. Cancer 2013;119:2541–2548. © 2013 American Cancer Society.

Abstract PD04-04: What is influencing breast conservation rates in the United States? Data from the National Accreditation Program of Breast Centers

Abstract INTRODUCTION: Breast conservation (BC) rates have been utilized as a quality metric, yet mastectomy rates have been noted to be increasing nationwide. The purpose of this study was to evaluate the factors associated with BC in 437 US breast centers surveyed by the National Accreditation Program of Breast Centers (NAPBC). METHODS: From 2006 to 2010, 437 breast centers across the US were surveyed by the NAPBC. At each center, annual data regarding BC rates were reported in the Survey Application Record (SAR) for patients with Stage 0-II breast cancer. We evaluated characteristics of breast centers including geographic location, volume of patients treated, therapeutic modalities provided, and center organizational relationships. Non-parametric statistical analyses were performed to determine factors associated with BC rates in this cohort. RESULTS: Among the 437 breast centers surveyed from 2006–2011, data on 77,248 patients with Stage 0-II were reported. The median number of Stage 0-II breast cancer patients per center was 149 (range; 10–891). The median proportion of these patients who underwent BC was 64.8% (range; 33–100%). No significant differences in median BC rate was noted over the six years of the study (range; 64.2% in 2006 – 67.1% in 2011, p = 0.788). However, significant regional variations were noted in median BC rates: 62.2% in the West (N = 59 centers), 63.8% in the South (N = 145 centers), 64.1% in the Midwest (N = 118 centers), and 70.8% in the Northeast (N = 104 centers), p &amp;lt; 0.001. There was no difference noted in BC rates between high volume (≥ 150 Stage 0-II cases/yr) and low volume (&amp;lt; 150 Stage 0-II cases/yr) centers (median 65.1% vs. 64.6%, respectively, p = 0.584). No differences in BC rate was noted between centers that referred vs. provided implant-based (p = 0.259), TRAM flap (p = 0.069), latissimus dorsi flap (p = 0.108) or DIEP/free flap (p = 0.324) reconstruction. Similarly, there was no difference noted in BC rates between centers who referred vs. provided whole breast radiation therapy (p = 0.224) and accelerated partial breast irradiation (p = 0.964). Centers that were affiliated with a hospital (N = 195) had a lower rate of BC than those that were not (n = 232); median 63.9% vs. 66.3%, p = 0.037. The majority of centers surveyed were also accredited by the Commission on Cancer (CoC; N=395); however, no differences were noted between these centers and those who were not CoC accredited in terms of BC rates (64.9% vs. 65.8%, respectively, p = 0.748). In a multivariate linear regression model, both region (p = 0.008) and hospital affiliation (p = 0.004) remained significant independent predictors of BC. CONCLUSION: Across 437 US breast centers, data from 77,248 patients demonstrate a national BC rate of 64.8%. While the rate does not seem to be varying significantly over time, variation in BC was noted between regions and between centers associated with hospitals vs. not. Rates of BC do not vary, however, by center volume, availability of reconstruction or radiation, nor by CoC accreditation status. These data suggest that patient choice, rather than the availability of radiation and reconstruction, is the driving force in surgical decision-making. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD04-04.

Abstract A04: The California Breast Cancer Survivorship Consortium (CBCSC): Prognostic factors associated with racial/ethnic differences in breast cancer survival

Abstract Background: Racial/ethnic disparities in mortality among US breast cancer patients are well documented. Using 2000-2006 data from Surveillance, Epidemiology, and End Results (SEER) registries, relative risk [95% confidence interval (CI)] of breast cancer-specific mortality relative to non-Latina Whites was significantly higher for African Americans (1.5 [1.4,1.6]) and Latinas (1.1 [1.0,1.2]), and non-significantly lower (0.9 [0.8,1.0]) for Asian Americans after adjusting for diagnosis age, SEER registry, disease stage, estrogen/progesterone receptor (ER/PR) status, county level poverty/education index, and other factors (Breast Cancer Res Treat, 127:729–738). Reasons for these differences are not well-understood; individual lifestyle factors may explain these differences, but current knowledge of the role of lifestyle in disease prognosis is limited for African Americans, Latinas and Asian Americans. Methods: The CBCSC assembled interview and cancer registry data from six California-based breast cancer etiology or prognosis studies, resulting in 12,210 breast cancer patients diagnosed with primary invasive breast cancer (6501 non-Latina Whites, 2060 African Americans, 2032 Latinas, 1505 Asian Americans, 112 others) between 1993 and 2007. Clinical characteristics and mortality data were obtained from the California Cancer Registry (CCR). Demographics (education, birthplace, migration), family history of breast cancer, parity, smoking, alcohol consumption, and other interview data were harmonized and pooled. Cox proportional hazards regression of overall and breast-cancer specific mortality were used to estimate racial/ethnic differences in stage-specific survival. Results: Frequency of adverse tumor characteristics (stage, differentiation, ER/PR status, nodal status, tumor size) were highest in African Americans, followed by Latinas, Asian Americans and non-Latina Whites, generally in that order. Latinas had lower education and higher parity than other racial/ethnic groups, whereas family history of breast cancer and alcohol consumption were highest in non-Latina Whites, and smoking was highest in African Americans. In total, 3047 deaths (1570 breast cancer-related) were observed after a mean (SD) follow-up of 8.3 (3.5) years. Compared to non-Latina Whites, the hazard ratio (HR) and 95% CI for breast cancer specific mortality was 1.15 [0.98,1.34] for African Americans, 0.77 [0.64,0.92], for Latinas, and 0.57 [0.36,0.92], for Asian Americans (adjusting for age and characteristics available from the tumor registry). HRs were slightly attenuated by further adjustment for education, migration, smoking and other factors (1.12 [0.95,1.31], 0.84 [0.69,1.02], 0.61 [0.38,0.99], respectively). Analyses are ongoing to determine the effect of neighborhood contextual factors, physical activity, body size, and comorbidities on racial/ethnic disparities in breast cancer survival. Conclusions: The CBCSC is a unique resource of a large and racially/ethnically diverse breast cancer cohort that will allow joint consideration of a variety of clinical, lifestyle, and contextual factors in explaining the long-standing disparities in breast cancer survival. Funded by: California Breast Cancer Research Program Special Research Initiative (16ZB-8004). Citation Format: Cheryl LP Vigen, Scarlett Lin Gomez, Richard Sposto, Yani Lu, Marilyn L. Kwan, Esther M. John, Kristine R. Monroe, Theresa HM Keegan, Salma Shariff-Marco, Allison W. Kurian, Iona Cheng, Bette J. Caan, Valerie S. Lee, Janise M. Roh, Jane Sullivan-Halley, Leslie Bernstein, Anna H. Wu. The California Breast Cancer Survivorship Consortium (CBCSC): Prognostic factors associated with racial/ethnic differences in breast cancer survival. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A04.

Collaborative modeling of the impact of obesity on race-specific breast cancer incidence and mortality.

Obesity affects multiple points along the breast cancer control continuum from prevention to screening and treatment, often in opposing directions. Obesity is also more prevalent in Blacks than Whites at most ages so it might contribute to observed racial disparities in mortality. We use two established simulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate the impact of obesity on race-specific breast cancer outcomes. The models use common national data to inform parameters for the multiple US birth cohorts of Black and White women, including age- and race-specific incidence, competing mortality, mammography characteristics, and treatment effectiveness. Parameters are modified by obesity (BMI of ≥30 kg/m2) in conjunction with its age-, race-, cohort- and time-period-specific prevalence. We measure age-standardized breast cancer incidence and mortality and cases and deaths attributable to obesity. Obesity is more prevalent among Blacks than Whites until age 74; after age 74 it is more prevalent in Whites. The models estimate that the fraction of the US breast cancer cases attributable to obesity is 3.9–4.5 % (range across models) for Whites and 2.5–3.6 % for Blacks. Given the protective effects of obesity on risk among women <50 years, elimination of obesity in this age group could increase cases for both the races, but decrease cases for women ≥50 years. Overall, obesity accounts for 4.4–9.2 % and 3.1–8.4 % of the total number of breast cancer deaths in Whites and Blacks, respectively, across models. However, variations in obesity prevalence have no net effect on race disparities in breast cancer mortality because of the opposing effects of age on risk and patterns of age- and race-specific prevalence. Despite its modest impact on breast cancer control and race disparities, obesity remains one of the few known modifiable risks for cancer and other diseases, underlining its relevance as a public health target.

Relationship Between Mammographic Density and Breast Cancer Death in the Breast Cancer Surveillance Consortium

Women with elevated mammographic density have an increased risk of developing breast cancer. However, among women diagnosed with breast cancer, it is unclear whether higher density portends reduced survival, independent of other factors. We evaluated relationships between mammographic density and risk of death from breast cancer and all causes within the US Breast Cancer Surveillance Consortium. We studied 9232 women diagnosed with primary invasive breast carcinoma during 1996-2005, with a mean follow-up of 6.6 years. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS) density classification. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression; women with scattered fibroglandular densities (BI-RADS 2) were the referent group. All statistical tests were two-sided. A total of 1795 women died, of whom 889 died of breast cancer. In multivariable analyses (adjusted for site, age at and year of diagnosis, American Joint Committee on Cancer stage, body mass index, mode of detection, treatment, and income), high density (BI-RADS 4) was not related to risk of death from breast cancer (HR = 0.92, 95% CI = 0.71 to 1.19) or death from all causes (HR = 0.83, 95% CI = 0.68 to 1.02). Analyses stratified by stage and other prognostic factors yielded similar results, except for an increased risk of breast cancer death among women with low density (BI-RADS 1) who were either obese (HR = 2.02, 95% CI = 1.37 to 2.97) or had tumors of at least 2.0 cm (HR = 1.55, 95% CI = 1.14 to 2.09). High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics. Thus, risk factors for the development of breast cancer may not necessarily be the same as factors influencing the risk of death after breast cancer has developed.

Superparamagnetic PLGA-iron oxide microcapsules for dual-modality US/MR imaging and high intensity focused US breast cancer ablation

Organic/inorganic, hybrid, multifunctional, material-based platforms combine the merits of diverse functionalities of inorganic nanoparticles and the excellent biocompatibility of organic systems. In this work, superparamagnetic poly(lactic-co-glycolic acid) (PLGA) microcapsules (Fe3O4/PLGA) have been developed, as a proof-of-concept, for the application in ultrasound/magnetic resonance dual-modality biological imaging and enhancing the therapeutic efficiency of high intensity focused ultrasound (HIFU) breast cancer surgery in vitro and in vivo. Hydrophobic Fe3O4 nanoparticles were successfully integrated into PLGA microcapsules by a typical double emulsion evaporation process. In this process, highly dispersed superparamagnetic Fe3O4/PLGA composite microcapsules with well-defined spherical morphology were obtained with an average diameter of 885.6 nm. The potential of these microcapsules as dual contrast agents for ultrasonography and magnetic resonance imaging were demonstrated in vitro and, also, preliminarily in vivo. Meanwhile, the prepared superparamagnetic composite microcapsules were administrated into rabbits bearing breast cancer model for the evaluation of the in vivo HIFU synergistic ablation efficiency caused by the introduction of such microcapsules. Our results showed that the employment of the composite microcapsules could efficiently enhance ultrasound imaging of cancer, and greatly enhance the HIFU ablation of breast cancer in rabbits. In addition, pathological examination was systematically performed to detect the structural changes of the target tissue caused by HIFU ablation. This finding demonstrated that successful introduction of these superparamagnetic microcapsules into HIFU cancer surgery provided an alternative strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy of cancer.