Determining Breast Cancer Risk Research Articles

Determination of Breast Cancer Risk and Knowledge Levels in Women: The Case of Cyprus.

Breast cancer is the type of cancer that is seen all over the world and ranks first among female cancers in terms of incidence and cause of death. This research was conducted to determine the breast cancer risk level and breast cancer knowledge level in women living in Northern Cyprus. The study, which was planned as a relational survey, was carried out as web-based. The research was completed with 657 adult female participants living in Northern Cyprus who volunteered to participate in the study. In order to collect data, the first section includes the introductory features, the second section includes the "Breast Cancer Risk Assessment Form" for determining breast cancer risk levels, the third section includes the "Comprehensive Breast Cancer Knowledge Test" to determine the breast cancer knowledge levels of the participants, and the fourth section includes the "Champion Health Belief Model Scale" was used. It was determined that 95.2% of women were in the low risk group for breast cancer. The knowledge test mean score is 12.05, and it can be said that the scores obtained are above the average (min:4- max:18). It was found that 55.7% of the women knew how to do Breast Self-Examination (BSE), but only 15.4% of them regularly performed BSE every month. It was found that 80.9% of the women never had mammography and their knowledge scores increased with increasing education level (p< 0.001) and there was a significant relationship between non-smokers and their knowledge levels (p< 0.01). Despite the high scores of women in knowledge tests, it was observed that the frequency of applying BSE and having mammography was very low. Regardless of the risk factors for breast cancer, the importance of regular check-ups and BSE for every woman should be taught to women by health professionals, and group trainings should be planned for women who do not have training on this subject.

Abstract 283: Fibroblast diversity and immune microenvironment in pseudoangiomatous stromal hyperplasia (PASH): Associations with breast cancer risk

Abstract Benign breast disease (BBD) affects over one million women annually in the United States and is diagnosed in nearly half of all women during their lifetime. Pseudoangiomatous stromal hyperplasia (PASH), a common BBD subtype, is characterized by an overaccumulation of tissue fibroblasts. Current research suggests a pivotal role of the immune microenvironment in progression of BBD to breast cancer, suggesting its composition as a determinant of breast cancer risk. Our study evaluates whether fibroblast variations and immune microenvironment differences in BBD biopsies containing PASH lesions are associated with subsequent breast cancer development. We evaluated BBD biopsies from women who subsequently developed breast cancer (cases, N=5) or remained cancer-free (controls, N=5). Using Opal-based multiplex immunofluorescence (mIF) assays, we mapped expression of fibroblast markers linked to breast cancer associated fibroblasts (CAFs), including vimentin (VIM), smooth muscle actin (ACTA2), fibroblast specific protein-1 (S100A4/FSP1), fibroblast associated protein (FAP), integrin beta-1 (CD29/ITGB1), and platelet derived growth factor receptor beta (PDGFRβ) and markers of key immune cells (T cells: CD4, CD8; dendritic cells: CD11c; B cells: CD20; and macrophages: CD68) along with MKI67 as a proliferation marker. Our results revealed marked differences in fibroblast marker expression and immune cell populations between these groups in the normal lobules in the BBD biopsies. PASH cases showed elevated PDGFRβ and CD29/ITGB1 expression in VIM-positive fibroblasts, markers characteristic of CAF subtypes known to accumulate in more aggressive tumor microenvironments. Conversely, a higher percentage of FSP1+/VIM+ cells, similar to that of a different CAF subtype, was noted in the lobules of PASH controls. This difference in biomarker expression, along with corresponding variations in immune cell counts, suggests a complex interplay between fibroblast composition and immune response that ultimately modulate cancer risk in PASH-containing BBD tissues. Additionally, increased MKI67 expression in PASH cases potentially signals the higher likelihood of cancer development. This work advances our understanding of fibroblast heterogeneity in BBD and its implications for breast cancer risk and progression, and paves the way for innovative strategies to improve clinical outcomes for BBD patients to reduce their incidence of breast cancer. Citation Format: Nicole Cruz-Reyes, Matilde Rossi, Melody Stallings Mann, Bryan McCauley, Tanya Hoskin, Robert Vierkant, Stacey Winham, Amy Degnim, Mark E. Sherman, Derek C. Radisky. Fibroblast diversity and immune microenvironment in pseudoangiomatous stromal hyperplasia (PASH): Associations with breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 283.

Multi-MicroRNA Analysis Can Improve the Diagnostic Performance of Mammography in Determining Breast Cancer Risk.

The objective of this study was to determine whether multi-microRNA analysis using a combination of four microRNA biomarkers (miR-1246, 202, 21, and 219B) could improve the diagnostic performance of mammography in determining breast cancer risk by age group (under 50 vs. over 50) and distinguish breast cancer from benign breast diseases and other cancers (thyroid, colon, stomach, lung, liver, and cervix cancers). To verify breast cancer classification performance of the four miRNA biomarkers and whether the model providing breast cancer risk score could distinguish between benign breast disease and other cancers, the model was verified using nonlinear support vector machine (SVM) and generalized linear model (GLM) and age and four miRNA qRT-PCR analysis values (dCt) were input to these models. Breast cancer risk scores for each Breast Imaging-Reporting and Data System (BI-RADS) category in multi-microRNA analysis were analyzed to examine the correlation between breast cancer risk scores and mammography categories. We generated two models using two classification algorithms, SVM and GLM, with a combination of four miRNA biomarkers showing high performance and sensitivities of 84.5% and 82.1%, a specificity of 85%, and areas under the curve (AUCs) of 0.967 and 0.965, respectively, which showed consistent performance across all stages of breast cancer and patient ages. The results of this study showed that this multi-microRNA analysis using the four miRNA biomarkers was effective in classifying breast cancer in patients under the age of 50, which is challenging to accurately diagnose. In addition, breast cancer and benign breast diseases can be classified, showing the possibility of helping with diagnosis by mammography. Verification of the performance of the four miRNA biomarkers confirmed that multi-microRNA analysis could be used as a new breast cancer screening aid to improve the accuracy of mammography. However, many factors must be considered for clinical use. Further validation with an appropriate screening population in large clinical trials is required. This trial is registered with (KNUCH 2022-04-036).

Application of Next Generation Sequencing technology to determine breast cancer risk among Bangladeshi women

Abstract Recent advancement in sequencing technology had led to the accurate and precise diagnosis of deadly diseases like breast cancer. Breast cancer is the second most common cancer in women, therefore, early diagnosis of this critical disease is important for prevention and therapeutic implications. BRCA1and BRCA2genes are significantly associated with breast cancer aetiology. Individuals carrying a germline mutation in BRCAgenes increase their chance of developing breast or ovarian cancer in women and pancreatic cancer in both sexes. The purpose of this study was to determine the germline mutations of BRACAamong the risk group of Bangladeshi women using Next Generation Sequencing (NGS). One hundred patients were selected randomly from the outdoor breast cancer clinic of DNA Solution Ltd. Using ‘Six-Point Scale’ twenty individuals were selected for BRCAgene mutation study. A clinical database was maintained to record personal and familial cancer history of the selected individuals. Personal identification was preserved according to Helsinki principals. Out of twenty enrolled individuals, seventeen individuals had a family history of cancer. However, upon sequencing data analysis, we observed only six patients carrying the pathogenic mutation of BRCAgene. This study only involved germline mutation and did not consider somatic mutation. Recent reports also suggest various genes other than BRCAare also associated with breast cancer occurrence. To our knowledge, this is the first time to use NGS technology to screen genetic mutations of breast cancer in Bangladesh. These data will help to develop early screening and possible prevention with better disease management in breast cancer. No Funding Support

Abstract P5-04-05: Predictors of guideline-incongruent breast cancer screening in an urban comprehensive cancer center

Abstract Background: Guideline-congruent breast cancer (BC) screening is imperative to systematically curb BC mortality. This study was conducted to identify predictors of BC screening behaviors congruent with guidelines from various nationally recognized organizations (e.g, American Cancer Society, National Comprehensive Cancer Network, American College of Radiology) among high- and average-risk women, and to elucidate the alternative screening behaviors of women who were incongruently screened. Methods: Medical records of 6,090 women who received at least two screening mammograms from January 2016 to March 2018 at the Karmanos Cancer Institute were reviewed to determine breast cancer risk status (classified by the Tyrer-Cuzick model) and breast density status to determine whether breast cancer screening was concordant with risk-driven screening guidelines. Breast density was determined by BI-RADS density scoring, with non-dense breasts defined by a score of A or B, and dense breasts as C or D. For women at average-risk of breast cancer, incongruent screening was defined as receiving supplemental imaging in the interval between screening mammograms. For high-risk women, incongruent screening was defined as not having a recommended supplemental image in the interval between screening mammograms. Further, we examined BC risk, breast density, age, and race as predictors for guideline-concordant screening. Results: The screening cohort included 73.3% Black and 26.7% White women of whom 86.5% were classified as average-risk, 7.7% intermediate risk and 5.8% high risk. Further analyses focused on women with average and high-risk of breast cancer. Among both average- and high-risk women, 390 (6.9%) were incongruently screened, however the rate of incongruent screening was much higher among high-risk vs. average risk women (97.7 vs. 0.9%, p&amp;lt; 0.01). Among average-risk women, incongruent screening was more likely among women with dense vs. non-dense breasts (2.0% vs 0.1%, p&amp;lt; .01). High-risk women were more likely to be incongruently screened if they had non-dense compared to dense breasts (99.5% vs 95.2%, p &amp;lt; .01). Younger women more likely to be incongruently screened among average-risk women (55.11 [SD = 10.24] vs 62.20 [SD = 9.73]; t5267 = 4.87, p &amp;lt; .01, d = 0.73), whereas older women were more likely to be incongruently screened among high-risk women, although this difference was not statistically significant (52.38 [SD = 7.27] vs 47.50 [SD = 8.57]; t351 = 1.87, p = .06, d = 0.67).There was no significant impact of race and incongruent screening for individual risk-level categories. With the exception of rendering the age effect non-significant, preliminary multivariable analyses did not significantly change the results. Further analyses will be conducted to assess the relationship between predictive factors and incongruent screening. Conclusions: An apparent lack of adherence to evidence-based screening guidelines for BC has led to underutilization of supplementary breast imaging for women at high-risk for BC. Further interventions are needed to promote increased supplemental imaging for this group of women. Citation Format: Alexandra Wehbe, Madeleine Gonte, Suzanne O’Neill, Alit Amit-Yousif, Kristen Purrington, Mark Manning, Michael Simon. Predictors of guideline-incongruent breast cancer screening in an urban comprehensive cancer center [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-04-05.

Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: A Reappraisal.

The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case-control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer. A research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n = 4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer. In the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34-0.55; P < 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87-1.70; P = 0.26). The inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk. Oophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.

Association between obesity with pattern and length of menstrual cycle: The role of metabolic and hormonal markers

ObjectivesTo evaluate in a sample of Chilean adult women, the association between adiposity markers with pattern and length of the menstrual cycle, assessing the influence of metabolic markers and hormones in this relationship. Study designWe conducted a cross-sectional study involving 401 premenopausal women belonging to the DERCAM study (Determinants of Breast Cancer Risk) from Santiago, Chile. The menstrual cycle pattern was defined as regular or irregular, while menstrual cycle length was categorized as short (≤25 d), normal (26–31d), and long (≥32d). Adiposity markers included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and body fat percentage (BFP). Insulin, sex-hormone-binding globulin (SHBG), estrone (E1), estradiol (E2), androstenedione (A2), follicle-stimulating hormone (FSH) and progesterone were measured in the follicular phase of the menstrual cycle. ResultsThere was no association between adiposity markers and cycle patterns. However, after all, metabolic and hormonal adjustments, women in the third tertile of BFP (RRR = 2.63; 95 % CI: 1.21.5.69) were more likely to have longer menstrual cycles. ConclusionWomen with high BFP presented a higher risk of having irregular menstrual cycles, which was an indicator of reproductive disorders; this relationship could be partially mediated by hormonal markers, especially SHBG, E1, and insulin levels.

Abstract PS3-13: Non-invasive screening for breast cancer risk based on circulating ensembles of tumor associated cells

Abstract Background: Common modalities for breast cancer screening include self-breast examination (SBE) for detection of palpable lumps as well as Mammography scans for detection of suspicious nodules or masses. While both approaches have low specificity, SBE has lower sensitivity for early stage cancers while mammography is associated with radiation exposure risks. A blood-based non-invasive approach for determination of breast cancer risk in asymptomatic individuals can facilitate early detection and improve prognosis and survival. Circulating Ensembles of Tumor Associated Cells (C-ETACs) are heterotypic clusters of malignant cells which originate in a tumor and are ubiquitously detected in peripheral blood of individuals with solid organ cancers. We present findings from two large-cohort prospective observational studies showing the suitability of C-ETACs for non-invasive, non-radiological screening for breast cancer. Methods: 15 ml of peripheral blood was collected from 14,962 female volunteers among whom 832 were suspected cases of breast cancer and 14,962 were asymptomatic individuals with age-associated risk of breast cancer. The 832 suspected cases underwent a foundational (first diagnostic) biopsy following collection of blood while the 14,962 asymptomatic individuals underwent a mammography scan following collection of blood. Peripheral blood mononuclear cells (PBMCs) were isolated from all blood samples and treated with an epigenetically activating treatment medium which exerts selective cytotoxicity towards non-malignant hematolymphoid cells and allows survival of apoptosis resistant malignant cells and their clusters (C-ETACs). C-ETACs were defined as clusters of 3 or more cells which were EpCAM+, PanCK+ and CD45+/-. Results: Among the 832 suspected cases, 779 were eventually diagnosed with breast cancer and 53 with benign breast conditions. C-ETACs were detected in 701 / 779 cases of breast cancer (90.0% sensitivity) with comparable detection rates in metastatic (365/408 = 89.5%) as well as non-metastatic (336/371 = 90.6%). C-ETACs were also detected in 1 / 53 (1.9%) cases of benign breast tumor. Among the asymptomatic cohort of 14,130, C-ETACs were detected in 657 cases (4.7%), which included 509 / 10,859 (4.7%) individuals with BIRADS 1 and in 148 / 3,271 (4.5%) of individuals with BIRADS ≥2. These individuals have been advised clinical follow-up. Conclusions: We show that C-ETACs are ubiquitous in breast cancers and rare in individuals with benign conditions as well as asymptomatic individuals. Being derived from the tumor mass, C-ETACs are specific for cancer and thus provide direct visual evidence of malignancy in cancer cases and risk of malignancy in asymptomatic cases. The non-invasive nature of the approach is well suited for screening of large asymptomatic populations for breast cancer. Citation Format: Dadasaheb Akolkar, Darshana Patil, Pradip Fulmali, Pooja Fulmali, Revati Patil, Archana Adhav, Shoeb Patel, Sachin Apurwa, Sushant Pawar, Harshal Bodke, Vishal Ranjan, Rohit Chougule, Pradyumna Shejwalkar, Shabista Khan, Raja Dhasarathan, Pradip Devhare, Sanket Patil, Vineet Datta, Cynthe Sims, Stefan Schuster, Jatinder Bhatia, Chirantan Bose, Ajay Srinivasan, Rajan Datar. Non-invasive screening for breast cancer risk based on circulating ensembles of tumor associated cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-13.

Abstract NG15: Investigation of relationships between breast cancer risk factors and bilateral mammographic breast density asymmetry among women undergoing diagnostic image-guided breast biopsies

Introduction: The etiology of breast cancer remains an area of ongoing investigation. Improving our understanding of factors associated with breast cancer development will strengthen the utility of risk prediction strategies and improve risk stratification. Mammographic breast density remains one of the most influential breast cancer risk factors, with 4 to 6 fold elevated risk observed among women with the highest compared to the lowest levels. These associations have consistently been observed irrespective of the method (visual or automated), used to quantify breast density, showing the robustness of the associations. An understudied breast cancer risk factor is the bilateral asymmetry of mammographic features, with prior studies suggesting that women with higher levels of breast asymmetry may be at elevated breast cancer risk. Increasingly, studies are recognizing the potential of bilateral breast asymmetry defined by mammographic breast density in determining breast cancer risk. Recently, Eriksson and colleagues highlighted a strong influence of breast asymmetry within a model they developed to predict short-term breast cancer risk among women attending breast screening. They observed that the contribution to the model of asymmetry in mammographic breast density, microcalcifications, and masses between the breasts was as substantial as the total number of microcalcifications and masses found within a mammogram, indicating that differences between the breasts may be an important risk marker. To help further understand associations between breast cancer risk factors and asymmetry of breast density, particularly among women at elevated risk for breast cancer, we evaluated risk factor relationships with the bilateral asymmetry of volumetric measures of global and local breast density across the spectrum of premalignant and invasive breast cancer diagnoses. Methods: This study included 882 women enrolled as part of the National Cancer Institute9s Breast Radiology Evaluation and Study of Tissues (BREAST)-Stamp Project (2007-2010). The BREAST-Stamp Project is a cross-sectional molecular epidemiologic study that aims to understand how novel breast density measures are related to breast cancer etiology. Women were enrolled if they were referred for diagnostic image-guided breast biopsy following an abnormal mammogram at the University of Vermont Medical Center, and had not previously been diagnosed or treated for cancer, undergone breast surgery within one year or received chemoprevention. Risk factor data were collected at study enrolment via interview and self-administered questionnaires. Breast density measures were estimated using Single X-ray Absorptiometry (SXA), a technique in which an SXA breast density phantom was affixed to the compression paddle of the mammography machine during routine mammography so that it was included in the X-ray field. It served as a reference standard to estimate volumetric breast density. Breast density was assessed using pre-biopsy craniocaudal full-field digital mammograms of both the ipsilateral (affected) and contralateral (unaffected) breast. Firstly, global density from each laterality was determined as percent fibroglandular volume (%FGV). Secondly, localized volumetric density measures were estimated following identification of the biopsy site on the ipsilateral pre-biopsy mammogram by the study radiologist and identifying the corresponding site on the contralateral mammogram. The SXA estimated %FGV in a perilesional volume twice the size of, but excluding, the biopsy target, centered at the biopsy site. Previous estimates of reproducibility for the SXA test phantoms demonstrated a repeatability SD of 2%, with a ±2% accuracy for the entire thickness and density ranges. Breast density asymmetry was defined as an absolute bilateral difference in measures when subtracting the breast density measures of the contralateral breast from the ipsilateral measures. Spearman9s correlations (rho) examined associations between breast density measures of the left and right breasts. To determine relationships between breast cancer risk factors (defined as categorical variables) and measures of bilateral breast density asymmetry, analysis of covariance (ANCOVA) models (PROC GLM) were used. Analyses were conducted at the per woman level using SAS. Probability values of Citation Format: Maeve Mullooly, Shaoqi Fan, Ruth M. Pfeiffer, Brian Sprague, Pamela M. Vacek, Donald L. Weaver, John A. Shepherd, Amir Pasha Mahmoudzadeh, Jeff Wang, Serghei Malkov, Jason M. Johnson, Sally D. Herschorn, Gretchen L. Gierach. Investigation of relationships between breast cancer risk factors and bilateral mammographic breast density asymmetry among women undergoing diagnostic image-guided breast biopsies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr NG15.

The Relationship between Risk Levels of Breast Cancer and Use of Early Diagnosis and Screening Services in Healthcare Workers in Turkey.

Background:This study aimed to determine the factors affecting early diagnosis and screening behaviors of healthcare workers concerning breast cancer and the breast cancer risk levels using the risk identification model and to evaluate the relationship between breast cancer risk levels and early diagnosis and screening behaviors.Methods:Overall, 466 healthcare workers from Balikesir Province, Turkey participated in this cross-sectional study. Data were collected thanks to a questionnaire prepared by the researchers. Cuzick-Tyrer model was utilized to determine breast cancer risk levels.Results:78.1% of the healthcare workers regularly perform breast self-examination (BSE), 11.6% had clinical breast examination (CBE), 7.7% had breast ultrasound scan and 4.5% had mammography. BSE behavior increased, as education level got higher. Mammography screening behavior increased in those aged 40 yr and older and those with breast or ovarian cancer history in their family. There was not any relationship between breast cancer risk levels and early diagnosis and screening behaviors.Conclusion:Early diagnosis and screening behaviors of healthcare workers were low concerning breast cancer. Age, education level and family history are the most prominent factors affecting early diagnosis and screening behaviors of healthcare workers. Informing healthcare workers on breast cancer risk factors and screening can make positive contributions to them and the public through them.

The Menstrual Cycle Related Hormone Variations and Breast Cancer Risk: A Novel Theory

Background: The cumulative and excessive exposures to estrogen contributing to increased risk of breast cancer may be misleading. Methods: We proposed a novel theory to highlight that exposure to unstable estrogen levels may play a critical role in determining breast cancer risk among females as the change of endocrine environment may pose a risky environment to breast tissues for carcinogenesis. Particularly, we considered the menstrual cycle related estrogen variation (MCREV) as the primary hazard to breast cancer among females. Results: To describe MCREV, its intensity was defined as the difference between the highest and the lowest levels of estrogen within a menstrual cycle; its timing was defined as age at menarche and age at pregnancies (i.e. timing of cessation of exposure to this hazard); and its frequency and duration can both be defined as the total number of menstrual cycles, which is influenced by many factors including age of menarche, age of menopause, average length of one menstrual cycle, and durations and number of pregnancies and breastfeeding. Conclusions: The proposed MCREV theory may identify women at high-risk of breast cancer at an earlier age. The development of breast cancer might be weakened if suitable techniques to reduce the MCREV become clinically available. This novel theory opens a new door in breast cancer prevention and management.

Social determinants of breast cancer risk, stage, and survival.

Social determinants of health that have been examined in relation to breast cancer incidence, stage at diagnosis, and survival include socioeconomic status (income, education), neighborhood disadvantage, unemployment, racial discrimination, social support, and social network. Other social determinants of health include medical distrust, immigration, status, inadequate housing, food insecurity, and geographic factors such as neighborhood access to health services. Socioeconomic factors influence risk of breast cancer. For all racial/ethnic groups, breast cancer incidence rates tend to be positively associated with socioeconomic status. On the other hand, low socioeconomic status is associated with increased risk of aggressive premenopausal breast cancers as well as late stage of diagnosis and poorer survival. There are well-documented disparities in breast cancer survival by socioeconomic status, race, education, census-tract-level poverty, and access to health insurance and preventive care. Poverty is associated with other factors related to late stage at breast cancer diagnosis and poorer survival such as inadequate health insurance, lack of a primary care physician and poor access to health care. The results of this review indicate that social determinants such as poverty, lack of education, neighborhood disadvantage, residential segregation by race, racial discrimination, lack of social support, and social isolation play an important role in breast cancer stage at diagnosis and survival. To address these social determinants and eliminate cancer disparities, effective interventions are needed that account for the social and environmental contexts in which cancer patients live and are treated.

A novel method of determining breast cancer risk using parenchymal textural analysis of mammography images on an Asian cohort

Historically, breast cancer risk prediction models are based on mammographic density measures, which are dichotomous in nature and generally categorize each voxel or area of the breast parenchyma as ‘dense’ or ‘not dense’. Using these conventional methods, the structural patterns or textural components of the breast tissue elements are not considered or ignored entirely. This study presents a novel method to predict breast cancer risk that combines new texture and mammographic density based image features. We performed a comprehensive study of the correlation of 944 new and conventional texture and mammographic density features with breast cancer risk on a cohort of Asian women. We studied 250 breast cancer cases and 250 controls matched at full-field digital mammography (FFDM) status for age, BMI and ethnicity. Stepwise regression analysis identified relevant features to be included in a linear discriminant analysis (LDA) classifier model, trained and tested using a leave-one-out based cross-validation method. The area under the receiver operating characteristic (AUC) and adjusted odds ratios (ORs) were used as the two performance assessment indices in our study. For the LDA trained classifier, the adjusted OR was 6.15 (95% confidence interval: 3.55–10.64) and for Volpara volumetric breast density, 1.10 (0.67–1.81). The AUC for the LDA trained classifier was 0.68 (0.64–0.73), compared to 0.52 (0.47–0.57) for Volpara volumetric breast density (p < 0.001). The regression analysis of OR values for the LDA classifier also showed a significant increase in slope (p < 0.02). Mammographic texture features derived from digital mammograms are important quantitative measures for breast cancer risk assessment based models. Parenchymal texture analysis has an important role for stratifying breast cancer risk in women, which can be implemented to routine breast cancer screening strategies.

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality.

Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy. The metabolic changes identified are consistent with inborn-like errors of metabolism and define a continuum from normal controls to elevated risk to invasive breast cancer. Similar results were observed in other adenocarcinomas but were not found in squamous cell cancers or hematologic neoplasms. The findings describe a new early detection platform for breast cancer and support a role for pre-existing, inborn-like errors of metabolism in the process of breast carcinogenesis that may also extend to other glandular malignancies.Statement of Significance: Findings provide a powerful tool for early detection and the assessment of prognosis in breast cancer and define a novel concept of breast carcinogenesis that characterizes malignant transformation as the clinical manifestation of underlying metabolic insufficiencies.

Abstract P3-09-09: Assessing utility of breast cancer risk assessment tool in comparison to Tyrer-Cuzick model for determination of breast cancer risk and implications for chemoprevention

Abstract Background Despite findings that the Tyrer-Cuzick (IBIS Breast Cancer Risk Evaluation Tool or TC) model is more predictive of breast cancer risk than the Gail model (NCI maintained Breast Cancer Risk Assessment Tool or BCRAT), BCRAT is commonly clinically used as per the United States Preventive Services Task Force (USPSTF), with a 5-year risk for breast cancer (BC) of greater than 3% on BCRAT, the benefits of preventive medication likely outweigh the risks. We aimed to compare the models, 1: to see if a 10 year risk estimate per the TC model reliably correlated with the 3% 5 year risk per BCRAT, and 2: to analyze the subset of patients with atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) who are known both to be at high risk for breast cancer and to benefit from chemoprevention. Our hypothesis is that BCRAT has limited utility in risk estimation, and the most comprehensive model for risk estimation and clinical decision making is TC. Methods 200 women ages 35-64 women followed in benign breast clinic were included. Risk estimations were run using BCRAT, TC version 7 (v7) and TC version 8 (v8). A Pearson's Correlation test was conducted to investigate the relationship between the TC models and the BCRAT model. A p-value &amp;lt; 0.05 was considered statistically significant. Results Analysis showed a positive moderate-strength relationship between the TC v7 10-year risk and the 5-year BCRAT risk for this population (R = 0.468, P&amp;lt;0.001) and a positive moderate-strength relationship between the TC v8 10-year risk and the 5-year BCRAT risk (R = 0.550, P&amp;lt;0.001). A TC v7 risk of 8.09% (95% confidence interval (CI): 7.42-8.75) and a TC v8 risk of 8.54% (95% CI: 7.85-9.24) corresponded to a BCRAT risk of 3%. However, much error was present when assessing consistency and correlation between the models. A total of 36 patients were diagnosed with AH, 2 patients were diagnosed with LCIS and 7 patients were diagnosed with both AH and LCIS. 11 patients who had AH had an estimated 5-year risk per the BCRAT model of &amp;lt;3%. Two of these patients were pre-menopausal and African American and one was pre-menopausal and Hispanic. Of the remaining 8 patients, all were under the age of 60. Of the 30 patients who had a BCRAT 5-year estimated risk of BC of &amp;gt;3% but no AH or LCIS, 12 had two first degree relatives with breast cancer and 16 had a first-degree relative with BC and at least two benign breast biopsies. Conclusion BCRAT is limited and caution is warranted with its use in assessing risk and for counseling around chemoprevention benefit. There is not reliable correlation between the 5 year BCRAT risk estimate and the 10 year TC risk estimate. Chemoprevention should be discussed for patients with AH, LCIS or 2+ first degree relatives with breast cancer. Further, BCRAT may underestimate risk in minority populations and others with AH. For a limited group of patients with moderate risk, dual modeling may be clinically useful in making chemopreventive recommendations. Citation Format: Pederson HJ, Yanda C, Kline M, Stephens M, Goraya ST, Grobmyer SR, Kattan MW. Assessing utility of breast cancer risk assessment tool in comparison to Tyrer-Cuzick model for determination of breast cancer risk and implications for chemoprevention [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-09-09.

Female offspring birth weight is associated with Body Mass Index, waist circumference and metabolic syndrome in Latin American women at 10-years postpartum

AimsWe aimed to assess whether female offspring birth weight (BW) is associated with anthropometric and metabolic outcomes in Chilean mothers at 10-years postpartum. MethodsWe assessed data from 396 Chilean mother-daughter pairs participating in the longitudinal Chilean Growth and Obesity Cohort (GOCS) and Determinants of Breast Cancer Risk (DERCAM) studies. Multivariate linear and logistic regression models were performed to associate female offspring BW with maternal Body Mass Index (BMI), waist circumference, type 2 diabetes mellitus, metabolic syndrome and its components at 10-years postpartum. ResultsAt 10-years postpartum, 69% of mothers were overweight, 65% had central adiposity and 26% had metabolic syndrome. Adjusted linear regression models showed associations between female offspring BW and (1) maternal BMI (%Δ GM = 4.46; 95% CI 0.25–8.85); and (2) waist circumference (%Δ GM = 3.25; 95% CI 0–6.60). Adjusted logistic regression models showed associations between female offspring BW and (1) maternal metabolic syndrome (OR = 3.48; 95% CI 1.50–8.11); (2) central adiposity (OR = 2.37; 95% CI 1.08–5.22); and (3) hypertriglyceridemia (OR = 3.19; 95% CI 1.40–7.23). ConclusionsFemale offspring BW was associated with maternal anthropometric and metabolic outcomes at 10-years postpartum. Our findings add to the emerging evidence that offspring BW might be a potential indicator for future maternal anthropometric and metabolic risks.

Obesity, Dietary Factors, Nutrition, and Breast Cancer Risk.

To synthesize the critical role of obesity-associated inflammation, dietary factors, and nutrition in determining breast cancer risk. Obesity-associated inflammation is strongly linked to breast cancer risk and progression, largely via two processes: inflammatory pathways and dysregulated metabolism. Cytokine production in excess adipose tissues creates a chronic inflammatory microenvironment, which favors tumor development. Lifestyle factors, including diet, have long been recognized as important determinants of breast cancer risk and mortality. Obesity increases the risk of developing breast cancer in both pre- and postmenopausal women and also negatively affects breast cancer recurrence and survival. Poor dietary habits characterized by the high intake of refined starches, sugar, and both saturated and trans-saturated fats, as well as the low intake of omega-3 fatty acids, natural antioxidants, and fiber, modulate inflammation and, thereby, appear to be linked to increased risk of breast cancer and mortality.

Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide.

BackgroundMammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known.Methods and findingsWe examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35–85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (–0.46 cm [95% CI: −0.53, −0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was −0.24 cm (95% CI: −0.34, −0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (−0.38 cm [95% CI: −0.44, −0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature.ConclusionsDeclines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

Family history and risk of breast cancer: an analysis accounting for family structure

PurposeFamily history is an important risk factor for breast cancer incidence, but the parameters conventionally used to categorize it are based solely on numbers and/or ages of breast cancer cases in the family and take no account of the size and age-structure of the woman’s family.MethodsUsing data from the Generations Study, a cohort of over 113,000 women from the general UK population, we analyzed breast cancer risk in relation to first-degree family history using a family history score (FHS) that takes account of the expected number of family cases based on the family’s age-structure and national cancer incidence rates.ResultsBreast cancer risk increased significantly (Ptrend < 0.0001) with greater FHS. There was a 3.5-fold (95% CI 2.56–4.79) range of risk between the lowest and highest FHS groups, whereas women who had two or more relatives with breast cancer, the strongest conventional familial risk factor, had a 2.5-fold (95% CI 1.83–3.47) increase in risk. Using likelihood ratio tests, the best model for determining breast cancer risk due to family history was that combining FHS and age of relative at diagnosis.ConclusionsA family history score based on expected as well as observed breast cancers in a family can give greater risk discrimination on breast cancer incidence than conventional parameters based solely on cases in affected relatives. Our modeling suggests that a yet stronger predictor of risk might be a combination of this score and age at diagnosis in relatives.

Association between single nucleotide polymorphisms in the antioxidant genes CAT, GR and SOD1, erythrocyte enzyme activities, dietary and life style factors and breast cancer risk in a Danish, prospective cohort study

Exposure to estrogens and alcohol consumption - the two only well-established risk factors for breast cancer - are capable of causing oxidative stress, which has been linked to progression of breast cancer. Here, five functional polymorphisms in the antioxidant genes SOD1, CAT and GSR were investigated in 703 breast cancer case-control pairs in the Danish, prospective “Diet, Cancer and Health” cohort together with gene-environment interactions between the polymorphisms, enzyme activities and intake of fruits and vegetables, alcohol and smoking in relation to breast cancer risk. Our results showed that genetically determined variations in the antioxidant enzyme activities of SOD1, CAT and GSR were not associated with risk of breast cancer per se. However, intake of alcohol, fruit and vegetables, and smoking status interacted with some of the polymorphisms in relation to breast cancer risk. Four polymorphisms were strongly associated with enzyme activity, but there was no interaction between any of the studied environmental factors and the polymorphisms in relation to enzyme activity. Additionally, single measurement of enzyme activity at entry to the cohort was not associated with risk of breast cancer. Our results therefore suggest that the antioxidant enzyme activities studied here are not major determinants of breast cancer risk.