Lower Incidence Of Breast Cancer Research Articles

Societal costs and effects of implementing population-based mammography screening in Greenland

ABSTRACTWith a low breast cancer incidence and low population density, Greenland is geographically and organisationally challenged in implementing a cost effective breast cancer screening programme where a large proportion of the Greenlandic women will have to travel far to attend. The aim of this paper is to evaluate the cost effectiveness and cost utility of different strategies for implementing population-based breast cancer screening in Greenland. Two strategies were evaluated: Centralised screening in the capital Nuuk and decentralised screening in the five municipal regions of Greenland. A cost effectiveness and cost utility analysis were performed from a societal perspective to estimate the costs per years of life saved and per QALY gained. Two accommodation models for the women’s attendance were examined; accommodation in ordinary hotels or in patient hotels. The least costly accommodation model was the hotel model compared with the patient hotel model, regardless of screening strategy. The decentralised strategy was more cost effective compared with the centralised strategy, resulting in 0.5 million DKK per years of life saved (YLS) and 4.1 million DKK per quality-adjusted life year (QALY) gained within the hotel model. These ratios are significantly higher compared with findings from other countries. The sensitivity analysis showed a substantial gap between the most and least favourable model assumptions. The investigated strategies were all estimated to be extremely costly, mostly due to high transportation and accommodation costs and loss of productivity, and none would be accepted as cost-effective per YLS/QALY gained within a conventional threshold level. The least expensive strategy was regional screening with hotel accommodation.

Breast Cancer in Australian Indigenous Women: Incidence, Mortality, and Risk Factors

The Indigenous people of Australia face significant health gaps compared with the general population, with lower life expectancies, higher rates of death, and chronic illness occurring more often than in non-indigenous Australians. Cancer is the second largest contributor to the burden of disease with breast cancer being the most common invasive cancer diagnosed for females. Despite a lower breast cancer incidence compared with non-indigenous women, fatalities occur at an elevated rate and breast cancers have an earlier age of onset. For indigenous women there are also more advanced and distant tumours at diagnosis, fewer hospitalisations for breast cancer, and lower participation in breast screening. Concomitantly there are demographic, socio-economic and lifestyle factors associated with breast cancer risks that are heavily represented within Indigenous communities. The aim of this two-part narrative review is to examine the available evidence on breast cancer and its risk factors in Australian Indigenous women. Part One presents a summary of the latest incidence, survival and mortality data. Part Two presents the risk factors most strongly associated with breast cancer including age, place of residence, family risk, genetics, reproductive history, tobacco use, alcohol intake, physical activity, participation in screening and breast density. With increasing emphasis on personalized health care, a clear understanding of breast cancer incidence, survival, mortality, and causal agents within the Indigenous population is required if breast cancer prevention and management is to be optimized for Indigenous Australians.

Does hepatitis B virus infection cause breast cancer?

Lifestyle and family history are two of the most important risk factors for breast cancer (BC). However, these risk factors cannot explain the differences in the incidence and early BC onset among Chinese females compared to their western counterparts. We propose in this hypothesis the potential mechanism of indirect oncogenesis of hepatitis B virus (HBV) in causing BC through its persistence as occult infection and continuous replication with long term subtle liver damage. Estrogen is mainly deactivated in the liver and long term necro-inflammatory damage to liver may result in persistent high level of estrogen, which is a dominant risk factor for BC. HBV may also directly affect the breast cells through its cis and trans effects of HBx which may act as oncoprotein. Given the recognised aetiologic association between oestrogen and breast cancer risk, there is biological plausibility that dietary soy and vegetable intake which is rich in the Chinese diet may have anti-carcinogenic effect on the breast. The seemingly conflicting phenomenon of early age onset and lower BC incidence in China might be due to wide imbalance in the amount of exposure to carcinogenic factor (e.g., HBV infection) for decades and the carcinoprotective exposure levels (e.g., isoflavonoids and flavonoids intake). For example, the increase in carcinoprotective levels would lead to lower incidence of breast cancer and vice versa. Although the focus of this personal view is on HBV, this by no means negates the roles of other known risk factors in breast-cancer development. Characterisation of the role of HBV in BC could potentially benefit Chinese females by decreasing incidence and increasing overall survival.

Adherence to diet, physical activity and body weight recommendations and breast cancer incidence in the Black Women's Health Study.

Adherence to cancer prevention recommendations has been associated with lower incidence of breast cancer in previous studies, but evidence in African American women is limited. This project evaluated the association between adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and breast cancer incidence among African American women. The Black Women's Health Study (analytic cohort = 49,103) is an ongoing prospective cohort study of African American women, ages 21-69 years at baseline (1995). Adherence scores for seven WCRF/AICR recommendations (adherent = 1, partial adherence = 0.5, non-adherence = 0) were calculated using questionnaire data and summed for overall (maximum = 7) and diet only (maximum = 5) scores. Associations between baseline and time-varying adherence scores and breast cancer incidence (N = 1,827 incident cases through 2011) were evaluated using proportional hazards regression. In this cohort, 8.5% adhered >4 recommendations. Adherence at baseline was not associated with breast cancer incidence. Higher overall time-varying adherence (per 0.5 point increase) was associated with lower breast cancer incidence (HR: 0.90, 95% CI: 0.84-0.96). Adherence to physical activity, sugar beverage and red and processed meat recommendations were also associated with reduced risk. Adherence to the WCRF/AICR recommendations was low and may be associated with lower breast cancer incidence in African American women.

Phytoestrogen (+)-pinoresinol exerts antitumor activity in breast cancer cells with different oestrogen receptor statuses.

BackgroundConsumption of virgin olive oil (VOO) has been associated with a low breast cancer incidence. Pinoresinol is a phytoestrogen that is typically found in VOO. Considering the role of oestrogen in breast cancer development and progression, we investigated the potential antitumor activity of pinoresinol in breast cancer cells.MethodsTo address this question, we treated MDA-MB-231 (oestrogen receptor [ER] negative) and MCF7 (ER+) human breast tumour cells and MCF10A human mammary epithelial cells (ER-) with different concentrations of pinoresinol. The cytotoxic activity, cell proliferation, cell cycle profile, apoptosis induction, reactive oxygen species production and DNA damage were assessed.ResultsPinoresinol showed cytotoxic, anti-proliferative and pro-oxidant activity in human breast tumour cells, independent of their oestrogen receptor status. In addition, pinoresinol exerted antioxidant activity and prevented DNA damage associated with oxidative stress in human mammary epithelial cells.ConclusionsOverall, the results suggest that pinoresinol may have antitumor activity in human breast cancer cells independently of oestrogen receptor status. Furthermore, the results show that the pinoresinol has the typical characteristics of a chemopreventive compound.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1233-7) contains supplementary material, which is available to authorized users.

Reducing Breast Cancer Recurrence: The Role of Dietary Polyphenolics.

Evidence from numerous observational and clinical studies suggest that polyphenolic phytochemicals such as phenolic acids in olive oil, flavonols in tea, chocolate and grapes, and isoflavones in soy products reduce the risk of breast cancer. A dietary food pattern naturally rich in polyphenols is the Mediterranean diet and evidence suggests those of Mediterranean descent have a lower breast cancer incidence. Whilst dietary polyphenols have been the subject of breast cancer risk-reduction, this review will focus on the clinical effects of polyphenols on reducing recurrence. Overall, we recommend breast cancer patients consume a diet naturally high in flavonol polyphenols including tea, vegetables (onion, broccoli), and fruit (apples, citrus). At least five servings of vegetables and fruit daily appear protective. Moderate soy protein consumption (5–10 g daily) and the Mediterranean dietary pattern show the most promise for breast cancer patients. In this review, we present an overview of clinical trials on supplementary polyphenols of dietary patterns rich in polyphenols on breast cancer recurrence, mechanistic data, and novel delivery systems currently being researched.

Intratechal Chemotherapy Treatment Through an Ommaya Reservoir Catheter for Meningeal Carcinomatosis: A Single-Centre Experience

Meningeal carcinomatosis is defined as tumour cells infiltration of leptomeninges and subarachnoid space. It is normally related with poor survival (2 - 5 months). The best multidisciplinary treatment for this condition is a matter of discussion. Patient's condition and the natural history of the disease should be considered in the decision making process. Retrospective cohort analysis of patients submitted to Ommaya Reservoir placement due to systemic solid tumour meningeal carcinomatosis between 2006 and 2014. Twenty three patients were included (19 females, four males) with median age of 56.1 ± 2.2 years. The primary tumour was: breast - 16 patients, lung - four patients, stomach, bladder and cervix - one patient each. No complications were seen (infection, intracranial haematoma or CSF fistula). The median survival was 26.4 ± 7.7 weeks, range between nine days and 118 weeks (21/23 patients). Male gender was related to poor prognosis in crude analysis (p value = 0.0032). Breast adenocarcinoma was related with better prognosis in adjust analysis (p value = 0.036, HR: 4.36 ± 3.06; 95% IC: 1.10 - 17.25). Longer time between initial tumour and meningeal carcinomatosis diagnosis was related to a better outcome but without statistical significance. Despite the low complication rate of Ommaya reservoir placement, the poor response to chemotherapy and the disease prognosis should be considered in patients with poor functional status. The relationship observed between the primary tumour and the overall survival supports that meningeal carcinomatosis should not be considered a disease by itself but always in the context of a systemic disease. The low incidence of breast cancer in male population might be related with it poorer prognosis. Meningeal carcinomatosis has a poor prognosis. Breast adenocarcinoma, longer time between initial tumour and meningeal carcinomatosis diagnosis, and age < 60 years were related with longer survival.

Breast Cancer: Detection Markers, Prognosis, and Prevention

Breast cancer is the common invasive cancer with high mortality worldwide. High incidence of breast cancer in South and central America, Southren, Northren, Westren Europe, Ocenia and North America. Lowest breast cancer incidence in Africa and Asia. Risk factors includes: female sex old age, lifestyle, oralcontraceptive, hormone replacement therapy, mutations in the breast cancer susceptibility genes BRCA1orBRCA2.alcohol intake, hereditary factors, and exposure to chemicals. Breast cancer occurs because of an interaction between external factor and genetically susceptible host. Frequent symptoms of breast cancer is typically a lump and lumps found in the lymph node in the armpits. Diagnosis by physical examination of the breast and mammography. Further tests include histopathological examination, breast cells grading by TNM systeme.g., Zero stage a precancerous or marker condition, stage 1- 3 within the breast and regional nodes, and stage four is metastatic stage. Management of breast cancer depends on the stage of the cancer and age of the patient. Usually treated with surgery, chemotherapy or radiation therapy or both. A multidisciplinary approach is preferable. Metastatic cancer has less favorable prognosis. Prognosis is usually the probability of progression-free survival(PFS) or disease free survival(DFS).Prevention include change in life style, maintaining healthy weight, less alcohol consumption, and intake of marine omega-3 and soy-based foods Prophylactic mastectomy(removal of both breasts) helps in people with BRCA1 and BRCA2 mutations. Early detection of breast cancer has better prognosis.

Abstract 1744: Is adherence to the WCRF/AICR cancer prevention recommendations associated with colorectal cancer in African American women in the Black Women's Health Study

Abstract Background: African American women are more likely to be diagnosed with colorectal cancer than women from other racial/ethnic groups. Differences in adherence to cancer prevention recommendations may contribute to disparities. Adherence to cancer prevention guidelines has previously been shown to be associated with lower breast cancer incidence, but previous study populations have included few African Americans. Objective: The purpose of this study was to evaluate adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and colorectal cancer incidence in the Black Women's Health Study (BWHS). Methods: In this ongoing prospective cohort of African American women (analytic cohort N = 49,103), 354 incident colorectal cancers were diagnosed between baseline (1995) and 2011. Adherence scores for seven WCRF/AICR recommendations (adherent = 1 point, non-adherence level 1 = 0.5 points, non-adherence level 2 = 0 points) were created using questionnaire data and summed to an overall adherence score (maximum = 7). Diet-specific recommendations were additionally summed for a diet only score (maximum = 5). Recommendation adherence and incidence of colorectal cancer combined and colon cancer only were evaluated using baseline and time-varying data in Cox regression models. Results: Guideline adherence was low with 8.5% of women (5.6% among women who later developed colorectal cancer) adhering to more than four recommendations at baseline. Adherence to a greater number of WCRF/AICR recommendations was not statistically significantly associated with colorectal cancer risk in time-varying or baseline models. In time-varying analyses, the HR (per 0.5 point increase) was 0.98 (95% CI: 0.84-1.15) and 0.51 (95% CI: 0.23-1.10) among women who adhered to &amp;gt;4 compared to &amp;lt;3 recommendations. Similarly, colon cancer evaluated alone was not statistically significantly associated with breast cancer incidence in time-varying (&amp;gt;4 vs. &amp;lt;3 recommendations HR = 0.54, 95% CI: 0.23-1.26) or baseline models (&amp;gt;4 vs. &amp;lt;3 recommendations HR = 0.72, 95% CI: 0.39-1.34). Regardless of modeling approach, adherence to dietary recommendations or individual recommendations was not associated with colon only or combined colorectal cancer risk. Conclusions: Further research in diverse populations is essential to evaluate the validity of existing recommendations, and to assess whether there are alternative recommendations that are more beneficial for colorectal cancer prevention in specific populations. Citation Format: Sarah J. O. Nomura, Chiranjeev Dash, Lynn Rosenberg, Jeffrey Yu, Julie R. Palmer, Lucile L. Adams-Campbell. Is adherence to the WCRF/AICR cancer prevention recommendations associated with colorectal cancer in African American women in the Black Women's Health Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1744.

Abstract 3936: Identification and validation of the potential biomarker insulin-like growth factor binding protein acid-labile subunit for breast cancer in African American women

Abstract Breast cancer is the most frequently diagnosed cancer in women, with an estimated 40, 730 breast cancer deaths in the US in 2015. African American (AA) women have a lower breast cancer incidence rate, but a higher breast cancer death rate, than non-Hispanic White women. Research indicates that breast tumor biology in AA women is different from that in Caucasian women. AA women are more likely to be diagnosed with breast cancer at an earlier age and with more aggressive form of the disease, characterized by higher grade and negative estrogen and progesterone receptor status. Because of the aggressive nature of these tumors and current lack of targeted therapies, identification of novel relevant protein markers is of great importance. The purpose of this study was to validate serum proteins that were previously identified by serum proteomic profiling in 22 serum samples by 2D-DIGE/MS analysis and a subset of samples by shotgun LC/MS technology. Methods and new data: The current study included serum samples from 15 African American breast cancer patients and 12 healthy controls. Patients were grouped into triple negative (TN), HER2 and Luminal A and B subtypes. Proteins of biological significance were validated using western blot analysis. For ceruloplasmin, and insulin-like growth factor binding protein acid-labile subunit (IGFBP-ALS), one-way ANOVA was used to compare mean density among the three groups. For Vitamin D Binding protein (VDB), a two-sample t-test was used to compare the density between the groups. Due to the small sample size, we have also conducted nonparametric tests. IGFBP-ALS was significantly lower in triple negative breast cancer patients (p = 0.016) and in HER2 (p = 0.025) subtypes. There was no significant difference in VDB protein in the luminal A and B subtypes (p = 0.98). Future efforts will focus on validating the identified panel of biomarkers to gain insight into their role(s) in the etiology of aggressive breast tumors. Funded by Susan G Komen for the Cure and SEED grant SPH. Citation Format: Padma P. Tadi Uppala, Carlos Garberoglio, Sharon Lum, Willie Davis, Hon-Chiu Eastwood Leung, Michael Liebman, Keiji Oda, Utkarsh P. Patel. Identification and validation of the potential biomarker insulin-like growth factor binding protein acid-labile subunit for breast cancer in African American women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3936.

Nanospray Drying as a Novel Tool to Improve Technological Properties of Soy Isoflavone Extracts.

Pharmacological evidences have correlated a low incidence of osteoporosis, breast cancer, cardiovascular disease, and colon cancer in Asian populations, high consumers of soya, to the properties of soy isoflavones, more specifically to daidzein and genistein. However, in spite of the potent biological activity, their poor water solubility has a strong negative effect on bioavailability. In this study, an innovative technique, nano spray drying, was used to obtain nanoparticles loaded with a soybean dry extract while carboxymethyl cellulose was used as the excipient. The optimization of the process conditions allowed for the manufacturing of stable nanoparticles with a mean size of around 650 nm, a narrow size distribution, and a high encapsulation efficiency (between 78 % and 89 %). The presence of carboxymethyl cellulose was able to stabilize the isoflavone extract and enhance its affinity with aqueous media, strongly increasing its permeation through biological membranes up to 4.5-fold higher than pure soy isoflavone extract raw material and twice its homologous minispray-dried formulation. These results are very useful for the administration of the extract, either topically or orally, suggesting that the isoflanones extract nanoparticulate powder obtained by nano spray drying has great potential to enhance extract bioavailability and could be used as an ingredient to be enclosed in dietary supplements and nutraceutical and cosmeceutical products.

The Risk of Breast Cancer in Women Using Menopausal Hormone Replacement Therapy in Taiwan.

Menopausal hormone replacement therapy (HRT) increases the risk of breast cancer in Western countries; however, there are fewer reports from the Asian population, which has a lower incidence of breast cancer. A population-based retrospective cohort study was conducted by analyzing longitudinal National Health Insurance claim data of a 200,000-person national representative cohort. A total of 22,929 women aged ≥45 years in 1997 without previous diagnosis of breast cancer were enrolled and stratified into two birth cohorts born before or after 1933. HRT prescriptions were traced in outpatient data files and incident breast cancer cases were identified from 1997 to 2004. The Cox proportional hazards model was used to analyze breast cancer hazard ratio (HR). HRT users were censored after they discontinued HRT. The results showed that women born during 1933–1952 had a twofold increased risk of breast cancer (HR = 2.10, 95% CI = 1.47–3.00) compared with women born before 1933, when adjusted for HRT use. When adjusted for the birth-cohort difference, HRT users had significantly increased breast cancer HR versus non-users after four years of use (adjusted HR = 1.48, 95% CI = 1.03–2.13); the HR further increased to 1.95 (95% CI = 1.34–2.84) after eight years of use. In conclusion, a longer duration of current HRT use was associated with a higher risk of breast cancer independent of the birth-cohort difference.

Risks of developing breast and colorectal cancer in association with incomes and geographic locations in Texas: a retrospective cohort study.

BackgroundNo study has been conducted to investigate the spatial pattern and association of socioeconomic status (such as income) with breast and colorectal cancer incidence in Texas, United States. This study aimed to determine whether median household income was associated with the risk of developing breast and colorectal cancer in Texas and to identify higher cancer risks by race/ethnicity and geographic areas.MethodsThis was a retrospective cohort study with an ecological component in using aggregated measures at the county level. We identified 243,677 women with breast cancer and 155,534 men and women with colorectal cancer residing in 254 counties in Texas in 1995–2011 from the public-use dataset of Texas Cancer Registry. The denominator population and median household income at the county level was obtained from the U.S. Bureau of the Census. Cancer incidence rates were calculated as number of cases per 100,000 persons and age-adjusted using the 2000 US population data. We used the ArcGIS v10.1 (geographic information system software) to identify multiple clustered counties with high and low cancer incidences in Texas.ResultsAge-adjusted breast cancer incidence rate in the highest median income quintile group was 151.51 cases per 100,000 in 2008–2011 as compared to 98.95 cases per 100,000 in the lowest median income quintile group. The risk of colorectal cancer appeared to decrease with increasing median income in racial/ethnic population. Spatial analysis revealed the significant low breast cancer incidence cluster regions located in southwest US-Mexico border counties in Texas.ConclusionsThis study demonstrated that higher income was associated with an increased risk of breast cancer and a decreased risk of colorectal cancer in Texas. There were geographic variations with cancer incidence clustered in high risk areas in Texas. Future studies may need to explore more factors that might explain income and cancer risk associations and their geographic variations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2324-z) contains supplementary material, which is available to authorized users.

Breast Cancer Risk Factors among Ugandan Women at a Tertiary Hospital: A Case-Control Study

Background: Although East Africa, like other countries in sub-Saharan Africa, has a lower incidence of breast cancer than high-income countries, the disease rate is rising steeply in Africa; it has nearly tripled in the past few decades in Uganda. There is a paucity of studies that have examined the relation between reproductive factors and breast cancer risk factors in Ugandan women. Objective: To determine breast cancer risk factors among indigenous Ugandan women. Methods: This is a hospital-based unmatched case-control study. Interviews were conducted between 2011 and 2012 using structured questionnaires. Patients with histology-proven breast cancer were recruited over a 2-year period. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 350 women were recruited; 113 were cases and 237 were controls. The mean age was 47.5 years (SD 14) for the cases and 45.5 years (SD 14.1) for the controls. The odds of breast cancer risk seemed lower for those who breastfed (adjusted OR = 0.04; 95% CI: 0.01, 0.18). There was no significance for early age at first full-term birth (adjusted OR = 1.96; 95% CI: 0.97, 3.96; p = 0.061), and urban residence carried no increased odds of breast cancer either (p = 0.201). Conclusion: Breastfeeding seems to be associated with reduced odds of breast cancer.

The impact of breast cancer-specific birth cohort effects among younger and older Chinese populations.

Historically low breast cancer incidence rates among Asian women have risen worldwide; purportedly due to the adoption of a "Western" life style among younger generations (i.e., the more recent birth cohorts). However, no study has simultaneously compared birth cohort effects between both younger and older women in different Asian and Western populations. Using cancer registry data from rural and urban China, Singapore and the United States (1990-2008), we estimated age-standardized incidence rates (ASR), annual percentage change (EAPC) in the ASR, net drifts, birth cohort specific incidence rates and cohort rate ratios (CRR). Younger (30-49 years, 1943-1977 birth cohorts) and older women (50-79 years; 1913-1957 birth cohorts) were assessed separately. CRRs among Chinese populations were estimated using birth cohort specific rates with US non-Hispanic white women (NHW) serving as the reference population with an assigned CRR of 1.0. We observed higher EAPCs and net drifts among those Chinese populations with lower ASRs. Similarly, we observed the most rapidly increasing cohort-specific incidence rates among those Chinese populations with the lowest baseline CRRs. Both trends were more significant among older than younger women. Average CRRs were 0.06-0.44 among older and 0.18-0.81 among younger women. Rapidly rising cohort specific rates have narrowed the historic disparity between Chinese and US NHW breast cancer populations particularly in regions with the lowest baseline rates and among older women. Future analytic studies are needed to investigate risk factors accounting for the rapid increase of breast cancer among older and younger women separately in Asian populations.

Abstract B24: Regulation of DARC isoforms among ancestry groups and associations with aggressive breast cancer subtypes

Abstract Biological mechanisms that drive disparate incidences of aggressive breast cancer in women of African descent are still largely unknown. Despite the fact that White women are more often diagnosed with breast cancer, African-American women have more severe cases and more often die from their breast cancer. Certain clues surrounding the tumor behavior and aggressive nature of cancers in African Americans point to physiological contexts, perhaps even the immunological microenvironment of the cancer sites. We hypothesize that higher mortality rates, coupled with lower incidence of breast cancer in this population, compared to white women, suggests the susceptibility is not necessarily a predisposition to acquire cancer, but that once a malignant cell is formed, the physiological make-up of these individuals somehow drives the aggressive nature of the tumors. This would explain the poor prognosis and higher mortality rates. We further hypothesize that chronic pro-inflammatory status, and altered chemokine profiles in this population are a key to tumor progression disparities. These disparities are likely due to specific genetic differences. Specifically, we are investigating the role of the Atypical Chemokine Receptor (ACKR1/DARC) gene and its isoforms in influencing a woman's chance of developing aggressive breast cancer subtypes. We aim to demonstrate that altered expression of DARC isoforms play a role in breast cancer severity and tumor aggression by regulating the infiltration of specific immune cell types into the tumor environment, by altering the levels of specific chemokines in the breast. We are investigating how the Duffy null allele, prevalent in all women of African descent, affects the ability of regulatory transcription factors to properly express ACKR1/DARC in epithelial and lymphoblast cells. GATA1 has been shown to regulate DARC in erythrocyte lineages; however, our previous findings indicate that DARC expression on epithelial (tumor) cells correlate with specific immune cell infiltrates. We have found that there are significant differences in epithelial Gata3 expression, correlating with DARC expression levels among ancestry groups. Using bioinformatics techniques, and ChIP-PCR we aim to define more precisely the transcription factors responsible for DARC isoform regulation. Specifically, by integrating expression data and interaction data with databases such as HEFalMp and identifying enrichment of biological processes with tools such as DAVID, we will identify additional candidate transcription factors by measuring associations of candidate gene expressions with DARC, we will define biological pathways related to immunological and inflammatory responses and test the ability of the highest priority candidate transcription factors to regulate DARC using siRNA techniques. Once we know what transcription factors are involved with epithelial expression of DARC, we can develop tools to further investigate how DARC plays a role in tumor progression in women of African descent. Citation Format: Kathryn Vollum, Rebekah Hutchins, Andrea M. Brown, Crystal Perez, Melissa B. Davis. Regulation of DARC isoforms among ancestry groups and associations with aggressive breast cancer subtypes. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B24.

Abstract B25: Triple-negative breast tumors exhibit distinctive patterns of expression and subcellular localization of Insulin-like Growth Factor Binding Protein 6

Abstract African-American women of all ages have higher breast cancer mortality rates than Caucasian women, despite lower breast cancer incidence among African-American women over 40. While differences in socioeconomic status and access to healthcare may play a role in this disparity, the disproportionately high occurrence of aggressive, triple-negative breast tumors in African-American women suggests a biological link between ancestry and breast cancer prognosis. Interestingly, both African ancestry and breast tumor aggressiveness are associated with distinct transcript and protein expression levels of Insulin-like growth factor-II (IGF-II) and its binding partner, Insulin-like growth factor binding protein 6 (IGFBP6), and we have previously observed higher levels of IGFBP6 transcript and protein expression in African-American and Yoruba (African) HapMap cell lines when compared to Amish cell lines. To gain a better understanding of potential mechanisms underlying these associations, we have investigated the expression and subcellular localization of these proteins and their transcripts using qPCR and immunofluorescence (IF). Our qPCR data indicate lower IGFBP6 transcript expression in breast cancer cells relative to normal cells, with lower transcript levels in the ER positive breast cancer cells than in triple negative cells. Conversely, our IF data revealed higher levels of IGFBP6 protein in ER positive breast cancer cells than in triple negative breast cancer cells, suggesting that breast tumor subtypes may be associated with unique patterns of transcript and protein regulation in these genes. We also observed a distinctive pattern of IGFBP6 subcellular localization in the triple-negative cells in which aggregates of this protein are localized at the edge of the nucleus, and co-localized with IGF-II. We hypothesize that IGF-II will be more dispersed throughout the nucleus following si-RNA knockdown of IGFBP6. Taken together, these data suggest the possibility of a subtype-specific IGF-II/IGFBP6 complex in triple negative breast cancer. Further studies will assess how this complex may promote tumor aggression in triple-negative breast tumors by inhibiting IGFBP6's IGF-independent, pro-apoptotic qualities within the nucleus and/or prolonging the half-life of IGF-II, thus promoting cancer cell growth. Citation Format: DeJuana Ford, Rupali Hire, Elizabeth Howerth, Briana Bennett, Krissean Lea, Jillian Hood, Melissa Davis. Triple-negative breast tumors exhibit distinctive patterns of expression and subcellular localization of Insulin-like Growth Factor Binding Protein 6. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B25.

Cancer in indigenous populations: challenges and responses

Cancer in indigenous populations: challenges and responses

Abstract PD4-03: Adherence to diet, physical activity and body composition guidelines and breast cancer in the black women's health study

Abstract Background: While breast cancer incidence rates have declined in non-Hispanic Caucasian populations, rates have remained stable in African American women, who are often affected by more aggressive subtypes. Previous studies have found that adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations, and the similar American Cancer Society (ACS) guidelines, is associated with lower incidence of breast cancer. However, few African American women were included in these studies, and guidelines are based primarily on research among Caucasian women. Objective: To evaluate the association between adherence to the WCRF/AICR cancer prevention recommendations and breast cancer incidence among African American women. Design: The Black Women's Health Study is an ongoing prospective study of African American women from across the United States who were 21-69 years of age at baseline in 1995. They are followed biennially through health questionnaires. Among 49,103 women who were free of cancer at baseline and who provided relevant dietary and data on the baseline questionnaire, 1,827 incident cases of breast cancer were ascertained during follow-up through 2011. Questionnaire data on physical activity, body composition and diet were used to compute adherence scores for seven WCRF/AICR recommendations involving those factors. For each individual recommendation, participants were categorized as adherent (1 point), partially adherent (0.5 points) or non-adherent (0 points). Scores were summed to a total adherence score (maximum score: 7 points) and a diet only adherence score (maximum score: 5 points). Adherence scores (categorical and continuous) based on baseline data only and on time-varying data were assessed in relation to breast cancer incidence using Cox proportional hazards regression models, with control for potential confounding factors. Results: In the analytic cohort, 8.5% of participants had an adherence score of 4.5-7.0, while 46% had a score less than 3.0. For individual recommendations, 15.2% were adherent to body weight recommendations, 24.7% were adherent to physical activity, and 5.4% were adherent to more than 4 diet recommendations. Participants were most likely to adhere to the alcohol recommendation (94.3%). In the time varying model, higher overall adherence (per 0.5 unit increase) was associated with lower breast cancer incidence (HR: 0.90, 95% CI: 0.84-0.96), with greater adherence to diet overall, physical activity, sugar beverage intake, and red and processed meat recommendations all significantly associated with reduced risk. The adherence score based on baseline variables was not associated with significantly reduced risk (HR: 0.96, 95% CI: 0.90-1.02), although meeting physical activity recommendations was associated. Conclusions: Our findings suggest that adherence to the WCRF/AICR guidelines may lower risk of developing breast cancer in African American women. However, body weight and alcohol, factors that are widely considered important for breast cancer prevention appear to be less relevant in this population. Citation Format: Nomura SJO, Yu J, Dash C, Rosenberg L, Palmer J, Adams-Campbell L. Adherence to diet, physical activity and body composition guidelines and breast cancer in the black women's health study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD4-03.

Abstract P6-10-15: Lifelong vegetarianism and breast cancer risk in India: A multicentre case control study of 2101 women

Abstract Background Breast cancer is now the most commonly diagnosed malignancy in women in India with over 150,000 incident cases per year. Interest in the role of diet in the aetiology of breast cancer is stimulated by the observation of the lower incidence of breast cancer in Asian populations where the intake of animal products is lower than that of Western populations. Studies investigating this relationship to date in India have been of small size and provided conflicting results and therefore a large scale case-control study in India addressing this relationship is of interest. Methods Between 2011 and 2014 we conducted a multicentre hospital based case-control study in eight cancer centres in India. Eligible cases included women aged 30-70 years with a new diagnosis of primary invasive breast cancer (ICD10 C50). Eligible hospital based controls included the accompanying attendants of the women with breast cancer and patients in the general hospital without cancer. Information about diet, lifestyle, reproductive and socio-demographic factors were collected using interviewer administered structured questionnaires. Cases and controls were frequency matched on a age geography. Multivariate logistic regression models were used to estimate the odds ratio and 95% confidence intervals for the risk of breast cancer in relation to lifelong vegetarianism, following adjustment for other known risk factors for the disease. Results The study included 2101 cases and 2252 controls. The mean age at recruitment was similar for both cases (49.7 years) and controls (49.6 years). The mean number of children was similar for both cases (2.6) and controls (2.5) and 98% of the study population had ever breastfed. However significant differences were observed in the proportion of cases whose duration of breastfeeding was greater than six years compared to controls (22% versus 29%). Cases were significantly more likely to live in a town (23% versus 16%), have running water (84% versus 78%) and live in a permanent dwelling (88% versus 78%). The proportion of lifelong vegetarians among the cases was 29% compared to 25% amongst the controls. However, on multivariate analysis, with adjustment for known risk factors for the disease, the risk of breast cancer was the same amongst cases and controls (OR 1.01 (95% CI 0.87-1.19)). Conclusions The prevalence of the known reproductive and sociodemographic risk factors for breast cancer is similar in India as in other populations. To our knowledge, this is the largest study conducted in India investigating the relationship between lifelong vegetarianism and risk of breast cancer, taking into account known risk factors for the disease. These results show that lifelong exposure to a vegetarian diet does not decrease the subsequent risk of breast cancer. Citation Format: Gathani T, Barnes I. Lifelong vegetarianism and breast cancer risk in India: A multicentre case control study of 2101 women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-15.