Risk Factors For Breast Cancer Research Articles

Breast Cancer Risk After Bariatric Surgery and Influence of Insulin Levels: A Nonrandomized Controlled Trial.

Obesity and insulin are risk factors for breast cancer, and retrospective studies suggest bariatric surgery reduces breast cancer risk in women. However, long-term prospective data on breast cancer risk after bariatric surgery and the role of baseline insulin levels are lacking. To examine if bariatric surgery is associated with breast cancer incidence in women and if treatment benefit is modified by baseline insulin levels. The Swedish Obese Subjects (SOS) study was a nonrandomized intervention trial designed to investigate the long-term effects of bariatric surgery on obesity-related mortality and morbidity. Study recruitment took place between 1987 and 2001, and median (IQR) follow-up time was 23.9 years (20.1-27.1) years. The study was conducted at 25 public surgical departments and 480 primary health care centers in Sweden and included 2867 women aged 37 to 60 years and with body mass index 38 or greater (calculated as weight in kilograms divided by height in meters squared). In the surgery group (n = 1420), 260 women underwent gastric banding, 970 vertical banded gastroplasty, and 190 gastric bypass. The remaining contemporaneously matched control individuals (n = 1447) received usual obesity care. Breast cancer, the main outcome of this secondary report, was not a predefined outcome in the SOS study. Breast cancer events were identified in the Swedish National Cancer Registry. The study population comprised 2867 women with a mean (SD) age of 48.0 (6.2) years. During follow-up, there were 154 breast cancer events, 66 in the surgery group and 88 in the usual care group, and a decreased risk of breast cancer was observed in the bariatric surgery group (hazard ratio [HR], 0.68; 95% CI, 0.49-0.94; P = .019; adjusted HR, 0.72; 95% CI, 0.52-1.01; P = .06). The surgical treatment benefit on breast cancer risk was greater in women with baseline insulin levels above the median 15.8 μIU/L (HR, 0.48; 95% CI, 0.31-0.74; P = .001; adjusted HR, 0.55; 95% CI, 0.35-0.86; P = .008) compared to those below (HR, 0.95; 95% CI, 0.59-1.53; P = .84; adjusted HR, 1.01; 95% CI, 0.61-1.66; P = .97; interaction P = .02). This prospective clinical trial indicated a reduced risk of breast cancer after bariatric surgery in women with obesity. The surgical treatment benefit was predominantly seen in women with hyperinsulinemia. ClinicalTrials.gov Identifier: NCT01479452.

Exploring Awareness and Understanding of Breast Cancer Risk Factors, Screening, and Treatment among Females in Pakistan

Purpose: Breast cancer is a pressing concern in Pakistan, ranking as the second leading cause of death among women. Despite its increasing incidence, it often lacks adequate attention from policymakers and healthcare professionals. This oversight could have severe consequences. To effectively tackle this health crisis, a thorough understanding of breast cancer's prevalence, risk factors, diagnosis, treatment, and outcomes in Pakistan is crucial. Methodology: To assess the level of awareness and understanding of breast cancer among women, this study was conducted. A cross-sectional survey was conducted in the outpatient department of Fauji Foundation Hospital, Rawalpindi, involving 350 female patients. Data were collected using a pre-structured questionnaire and analyzed using SPSS Version 16.0. Findings: Descriptive statistics were used, and the results were expressed as percentages and presented graphically. The study found that 70% of women were aware of breast cancer. Furthermore, 74% of the patients were married, and 87% had children. Knowledge about signs, symptoms, diagnosis, and treatment of breast cancer was relatively high among the women surveyed. However, only 23% of women had knowledge about performing breast self-examinations, and 18% had heard about mammography. This study provides valuable insights into breast cancer awareness and prevention behaviors among women in Pakistan, with significant implications for theory, policy, and practice. The findings highlight gaps in knowledge and awareness, particularly regarding breast self-examinations and mammography screenings. Unique Contribution to Theory, Policy and Practice: Policy implications stemming from the study results include the need for targeted awareness campaigns, educational programs, and screening initiatives to improve breast cancer awareness and preventive behaviors among women in Pakistan. Policymakers should allocate resources towards these efforts and integrate breast cancer education into existing healthcare services and community outreach programs to ensure widespread dissemination of information and access to screening services.

Breast cancer risk assessment for prescription of Menopausal Hormone Therapy in women who have a family history of breast cancer

Background Menopausal Hormone Therapy (MHT) can alleviate menopausal symptoms but is associated with increased risk of breast cancer (BC). MHT prescription should be preceded by individualised risk/benefit evaluation; however, data outlining the impact of family history alongside different MHT therapeutic approaches are lacking. Aim To quantify the risks associated with MHT use in women with varying BC family histories of i) developing and ii) dying from BC. Design and setting An epidemiological modelling study (UK women). Method We used i) background risks of BC by age and family history, ii) relative risks for BC associated with MHT use, and iii) 10-year BC-specific net mortality rates to model the risk of developing and dying from BC between the ages of 50 and 80 in women with four different BC family history profiles: ‘average’, ‘modest’, ‘intermediate’, and ‘strong’. Results For a woman of ‘average’ family history taking no MHT, the cumulative BC risk (age 50-80) is 9.8%, and the risk of dying from the BC is 1.7%. Five years’ exposure to combined-cyclical MHT (age 50-55) increases these risks to 11.0% and 1.8%, respectively. For a woman with a ‘strong’ family history taking no MHT, the cumulative BC risk is 19.6%, and the risk of dying is 3.2%. With 5 years of MHT (age 50-55), this increases to 22.4% and 3.5%. Conclusion Both family history and MHT are associated with increased risk of BC. Estimates of the risks associated with MHT for women with different family histories can support decision-making around MHT prescription.

The relationship between demographic factors and known risk factors with breast cancer in women aged 30-69

Background: Breast cancer is one of the most important causes of cancer deaths in women. The present study was conducted to determine the relationship between demographic factors and known risk factors with breast cancer in women aged 30 to 69. Method: This case-control study was conducted with two matched and unmatched control groups. Three hundred fifty women aged 30 to 69 with breast cancer, 350 age-matched women without cancer, and 350 not age-matched women were included in the study. Controls were selected from the records of women whose breast cancer screening results were normal. Study subjects were evaluated regarding the risk factors for breast cancer. The data collection tool was a checklist including the risk factors investigated in the integrated health system (IHS). The collected data were analyzed utilizing SPSS22 software at a significance level of less than 0.05. Results: The average age in the case group was 46.63 ± 11.77 years and 49.61 ± 8.39 in the unmatched control group. The average age of marriage in the case group was 21.54 ± 4.31, and the average age of women at first pregnancy in the case group was 24.06 ± 3.39 years. In the case group, 163 people (46.57%) lived in the city, 221 people (63.14%) were over 40 years old, and 337 people (96.28%) were married. In multivariate analysis, the variable “age of marriage” 0.821 (0.691-0.976) and “age of first pregnancy” 1.213 (1.020-1.443) showed a significant relationship with breast cancer which were observed as predictors of breast cancer in comparison to the unmatched control group (P-value <0.05). Conclusion: The age of the first pregnancy and the type of delivery were observed as predictors of breast cancer. Therefore, by performing breast cancer screening in women who are exposed to these risk factors, early diagnosis of the disease and increasing the speed of their treatment can be significantly helped.

Aspirin Metabolites and Mammographic Breast Density in Premenopausal Women.

Studies investigating the associations of self-reported aspirin use and mammographic breast density (MBD) have reported conflicting results. We, therefore, investigated the associations of aspirin metabolites, with MBD in premenopausal women. We performed this study on 705 premenopausal women who had fasting blood draw for metabolomic profiling. We performed covariate-adjusted linear regression models to calculate the least squares means of volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) by quartiles of aspirin metabolites (salicyluric glucuronide, 2-hydroxyhippurate (salicylurate), salicylate, and 2,6-dihydroxybenzoic acid). Approximately 13% of participants reported taking aspirin in the past 12 months. Aspirin users had higher levels of 2-hydroxyhippurate (salicylurate), salicylate, and salicyluric glucuronide (peak area) than non-users, but only mean peak area of salicyluric glucuronide increased by both dose (1-2 tabs per day=1,140,663.7, and ≥3 tabs per day=1,380,476.0) and frequency (days per week: 1 day=888,129.3, 2-3 days=1,199,897.9 and ≥4 days=1,654,637.0). Aspirin metabolites were not monotonically associated with VPD, DV, or NDV. Given the null results, additional research investigating the associations of aspirin metabolites in breast tissue and MBD is necessary. Elucidating the determinants of MBD, a strong risk factor for breast cancer, can play an important role in breast cancer prevention. Future studies should determine the associations of non-aspirin non-steroidal anti-inflammatory drug metabolites with MBD.

Abstract PO5-09-08: Cancer Health Disparities among non-Hispanic African women: A systematic review of the disparities, reasons and probable intervention

Abstract Health equity places health inequities in historical and social context and calls for action to address injustice and enhance health. As an ethical and human rights value that drives us to end health inequities, health equality is defined as everyone having a fair and just opportunity to be as healthy as feasible. According to this perspective, structural discrimination and marginalization cause health disparities that can be avoided. If these issues are not resolved, social and economic injustices, bias, and unfavorable outcomes that affect all of us will continue to exist. The idea of cancer health equality recognizes that there is still considerable work to be done to change the social structures and historical momentum that have contributed to different cancer outcomes, and that this work can only succeed if it is done. In USA, non-Hispanic black women experience a complicated and multifaceted disparity in breast cancer incidence and outcome. It's possible that social, economic, and behavioral variables contribute to discrepancies. Black women are less likely to breastfeed after childbirth, statistically more likely to have diabetes, heart disease, and obesity, all of which are risk factors for breast cancer. Compared to white women, they are more likely to lack adequate health insurance or access to medical facilities, which could have an impact on screening, follow-up treatment, and therapy completion. It has become evident via more study that biology also plays a part. Black women are more likely to be diagnosed at younger ages and at higher rates with more aggressive subtypes of breast cancer, such as triple-negative breast cancer (TNBC) and inflammatory breast cancer. The National Institute on Minority Health and Health Disparities (NIMHD) established a research framework to characterize the multiple domains of influence (biological, behavioral, physical environment, sociocultural environment, and health care system) that may act across various levels of influence to impact health. A literature search was conducted using the National Library of Medicine's PubMed search engine. Triple negative breast cancer (TNBC) is a common malignancy in African American women. The incidence of TNBC is higher in women of African ancestry and is associated with overall poor prognosis. This disparity is due to the presence/absence of oncogenes/tumor suppressor genes, mutations and altered signaling pathways that might predispose premenopausal African American women to TNBC. Multiple socioeconomic factors influence the access to standard care, novel treatments and inclusion in clinical trials and contribute to overall prognoses. This review focuses on the epidemiology, molecular alterations, and treatment-related disparities in African Americans with breast cancer. This poster will elaborate the racial disparity in terms of breast cancer among the African-American women in USA, the reasons and it's effects on health equity. Citation Format: Tasnuva Khan Efa. Cancer Health Disparities among non-Hispanic African women: A systematic review of the disparities, reasons and probable intervention [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-08.

Abstract PO1-07-10: Blood Based Early Cancer Detection Assay

Abstract Background: Breast cancer screening programs utilizing mammography have been shown to be highly effective in identifying breast cancer in women over the age of 40. High breast density is an independent risk factor for breast cancer and makes mammograms more difficult to interpret, decreasing their sensitivity. In the spring of 2023, the FDA, who certifies all mammography facilities under the Mammography Quality Standards Act, updated its regulations to require that breast density status be reported to all individuals receiving a mammogram. The new guidelines now require individuals with dense breast tissue be notified of this status. The guidelines also recommend these women discuss additional screening options with their healthcare providers1. These additional screening options may include breast tomosynthesis, breast MRI, breast ultrasound, and/or molecular breast imaging. Many of these options require additional exposure to radiation, are expensive, and are not equitably available across the country. In addition, they all require a follow-up appointment. Compliance can be challenging given the top barriers to mammography cited include the need for transportation, child-care, and the ability to take time off from work2. Genece Health is developing a simpler and less expensive screening solution that identifies the presence of early to late-stage breast cancer using cfDNA from a single blood draw. The Genece Health assay utilizes an algorithm that leverages Artificial Intelligence and Machine Learning to analyze fragment size and end motif patterns in cfDNA as well as regional mutational density to detect presence of ctDNA originating from breast cancer. This algorithm provides highly sensitive and specific results in a preliminary data set. Methods: The preliminary data set, presented herein, is a cohort of over 50 retrospective breast cancer plasma samples and over 100 presumed normal samples. The breast cancer samples were collected at all stages of progression, from stage 0, or ductal carcinoma in situ (DCIS), through stage IV. The majority ( >50%) were from stage I breast cancer. 400 µL of double spun plasma, collected in Streck BCT devices, was processed to purify and isolate cfDNA. cfDNA was used to create WGS libraries that were sequenced on a NovaSeq 6000. Sequence data were analyzed using a bioinformatics pipeline that yields an ensemble probability that correlates to the presence or absence of ctDNA from breast cancer. Results: The Genece Health assay and algorithm performed with a specificity greater than 85%. With this specificity, the assay had a sensitivity greater than 85% in samples from stages II to IV and a slightly lower sensitivity in stage 0 and I samples. Follow-up analyses were conducted to stratify performance based on breast cancer type (e.g. invasive ductal carcinoma vs invasive lobular carcinoma) and HR, PR, and HER2 status (e.g. HER2-negatives vs HER2-positives). Conclusions: The presented preliminary data indicate that the Genece Health technology can be leveraged as a complement to mammography in indications, such as dense breast tissue, where there is an unmet need for an easy and cost-effective way to monitor for breast cancer. The ability to have a blood-based test to complement mammography could reduce the access barriers most cited by females in the United States. Follow-up studies with greater numbers of samples and additional training and optimizations of the algorithm will yield performance improvements that allow the assay to detect all types and stages of breast cancer.

Abstract PO4-05-11: Effects of body mass index on the treatment outcome of patients with metastatic breast cancer in the real world

Abstract Purpose: Metastatic/recurrent breast cancer has a relatively long survival compared to other cancers and depending on the biologic subtype, the treatment outcome is different. In general, obesity or overweight is associated with poor prognosis of breast cancer, but the relationship between body mass index (BMI) and prognosis in metastatic cases is not clear. The aim of this study is investigating the effect of BMI on survival outcome through long-term follow-up in single institution, retrospectively. Method: This study included the patients with metastatic/recurrent breast cancer who has been diagnosed from January 2000 to December 2022 in an institution. BMI was calculated based on weight at diagnosis of metastatic disease, divided into 4 groups according to Asian-Pacific classification, and clinical characteristics including biologic subtype and overall survival (OS) were retrospectively reviewed. The statistical analysis was performed using Kaplan-Meier survival analysis and Cox proportional hazard model. Result: A total of 679 patients were enrolled. Median age was 51 years-old (25~89), 672 patients (99.0%) were female and 425 patients (62.6%) showed pre-menopausal status. The frequencies of HR+, HER2, and TNBC subtype were 335 (50.7%), 191 (28.9%), and 135 (20.4%), respectively and the BMI classification was 33 (5.5%), 251 (41.6%), 124 (20.5%), 196 (32.4%) for underweight, normal, overweight, and obesity, respectively. During a median follow-up of 33.8 months, the median OS in each of the HR+, HER2+, and TNBC subgroups was 54.9 (95% CI 38.7-71.1), 62.8 (95% CI 47.8-77.8), and 20.8 months (95% CI 12.0-29.7). In univariate analysis, there was no statistically significant difference in OS according to BMI in whole patients, however, in the HER2-positive group, the underweight BMI group showed poor OS (p=0.045). In multivariate analysis, the factors affecting OS were age (HR 0.59, 95% CI 0.41-0.87, p=0.008), poor ECOG PS (HR 8.35, 95% CI 2.54-27.49, p< 0.001), TNBC subtype (HR 2.14, 95% CI 1.56-2.94, p< 0.001), visceral metastasis (HR 2.13, 95% CI 1.63-2.79, p< 0.001), 5% or more weight loss during treatment (HR 1.46, 95% CI 1.09-1.97, p=0.012) and obesity BMI group (HR 0.69, 95% CI 0.51-0.94, p=0.019). Conclusion: In the case of patients with metastatic/recurrent breast cancer, there is concern about an increase in body weight, a known risk factor for breast cancer, while receiving palliative aim treatment. For the past 20 years, the mainstay of treatment for metastatic/recurrent breast cancer has been cytotoxic chemotherapy or anti-HER2 agents, and in this case, the higher BMI group patients showed better treatment outcomes compared with normal BMI patients. Citation Format: Kyoung Eun Lee, Ahrong Ham, Sewon Lee, Jungmin Jo, Soo Ji Hong, Ji Eun Lee, Haena Lee, Sungchan Gwark, Jeongshin An, Hyun-Goo Kim, Jun Woo Lee, Joohyun Woo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee. Effects of body mass index on the treatment outcome of patients with metastatic breast cancer in the real world [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-11.

Abstract PO4-20-07: Dense Breast Tissue in a High-Risk African-American Woman with DCIS and Nodal Metastasis of Intra-ductal Carcinoma: A Case Report and Discussion on the Current USPSTF Draft Recommendation

Abstract Introduction and objectives: The incidence of breast cancer (BC) in younger women has increased in recent years, raising the discussion on adjustments to screening recommendations. This past May, a new draft recommendation to the USPSTF guidelines for BC screening adjusted the age of screening from 50 to 40. However, there is still insufficient evidence to recommend adjusted screening guidelines for patients at increased risk including ethnic minorities with higher mortality and women with dense breasts. The paucity of trials and reviews for many of these at-risk groups may be leading to later diagnosis and poorer outcomes. This case highlights the importance of clinical judgment when screening patients whose presentation lies outside the guidelines. Clinical Case: A 29-year-old AAW with past medical history of bipolar disorder presents to her primary care physician in April 2023 with concern for left breast mass. Patient was previously on risperidone and Depakote for her bipolar disorder one year prior which resulted in drug-induced amenorrhea and breast tenderness with evidence of elevated prolactin. She was taken off her medication with return of her menses, but breast tenderness persisted for three months. During this time, she noticed a palpable breast mass. Family history is not significant for breast cancer. Breast ultrasound and mammography revealed “extremely dense” breast tissue bilaterally. Imaging significant for 7.6 × 6.2 × 6.3 cm irregular mass in the lower inner quadrant of the left breast with pleomorphic calcifications. Biopsy subsequently performed with breast pathology significant for ER+/PR- ductal carcinoma in situ. However, lymph node pathology showed evidence of invasive ductal carcinoma raising question of diagnosis of possible occult breast cancer versus breast cancer with axillary metastasis. PET CT did not show evidence of metastatic disease. She was started on neoadjuvant chemotherapy. Discussion and Conclusion: It is well known that African American women (AAW) are at increased risk for mortality due to BC, aggressive secondary BC, and for high-risk tumor biology. Additionally, AAW generally have more dense breast tissue, another risk factor for BC. Dense breast tissue can make it more difficult to characterize high-risk lesions on screening modalities. In regard to this patient, her dense breast tissue may obfuscate characterization of areas of possible primary cancer being the cause of her nodal metastasis. Current guidelines do not take these well-known associations and risk factors into account. A separate treatment algorithm may be required to work up a patient from high-risk groups such as this patient case. It is crucial that future guidelines on screening should incorporate specific risk factors which would help detect BC earlier in vulnerable populations. Citation Format: Vinita Akula, Jessica Jones. Dense Breast Tissue in a High-Risk African-American Woman with DCIS and Nodal Metastasis of Intra-ductal Carcinoma: A Case Report and Discussion on the Current USPSTF Draft Recommendation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-07.

Abstract PO4-08-06: Causal Relationships and Familial Aggregation of Mammogram Risk Scores: Insights from Breast Cancer in Twins and Families

Abstract Background: Mammogram risk scores based on texture and density, determined by brightness thresholds, are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. This study aimed to investigate the causal relationships between these intercorrelated risk scores and the familial aggregation of a texture-based mammogram measure, shedding light on the relevance to breast cancer aetiology. Methods: We analysed data from the Australian Mammographic Density Twins and Sisters Study, including 3195 breast-cancer-free women from 1519 families. The dataset comprised 527 pairs of monozygotic (MZ) twins, 271 pairs of dizygotic (DZ) twins, and 1599 sisters. The average age at mammography for sister pairs ranged from 40 to 70 years. Mammogram risk scores based on texture (named Cirrus) and three density-defined areas (light, bright, and brightest) that were spatially independent were generated. The Inference about Causation from Examination of Familial Confounding (ICE FALCON) method was employed for causal inference. Familial aggregation and the variance of Cirrus were assessed as a function of age using a multivariate normal model for pedigree analysis. The classic twin model was employed but allowing for varying shared environmental effects among different sister pairs. The single-nucleotide polymorphism (SNP)-based heritability was estimated using genetic variants from both closely and distantly related individuals. Model fits were compared using likelihood ratio tests and the Akaike Information Criterion. Results: Causal analysis using ICE FALCON revealed significant positive causal effects, with Cirrus, light areas, and bright areas influencing the brightest areas (accounting for 34%, 55%, and 85% of the associations, respectively). Similarly, light areas and bright areas demonstrated causal effects on Cirrus (accounting for 37% and 28% of the associations, respectively). No age-related differences in familial correlations or Cirrus variance were found for women aged 40 to 70 years. Familial correlations were estimated at 0.51 (0.03) for MZ pairs and 0.16 (0.03) for combined DZ and non-twin sister pairs, with no significant difference between DZ and non-twin sister pairs (P=0.3). Additive genetic effects accounted for up to 32% (5%) of the variance, consistent with SNP-based heritability estimates of 36% (12%). MZ-specific environmental effects contributed to at least 20% (3%), while shared environmental effects for DZ and non-twin sibling pairs accounted for less than 40% of that for MZ pairs. Conclusion: In a mammogram, the lighter (less dense) areas causally influence the brightest (highly dense) areas, including through textural features. These causal relationships provide insights into the relative importance of different mammogram features in breast cancer aetiology. For example, the brightest areas are more aetiologically important for screen-detected breast cancer, while the light areas are more aetiologically important for interval breast cancer. Additionally, specific textural features capture aetiologically independent breast cancer risk information from dense areas. We also confirm the partial heritability of Cirrus, the texture-based mammogram measure, substantially influenced by environmental factors (familial and non-familial). As well as genetic factors, Cirrus could be determined by factors operating at times of life when MZ pairs share their environments to a greater extent than do DZ and non-twin sisters, starting in utero and prior to adulthood, and remaining constant thereafter. These insights from twin and family data enhance our understanding of mammogram risk scores and their implications for breast cancer risk assessment. Citation Format: Zhoufeng Ye, Shuai Li, Gill Dite, Tuong Nguyen, Robert MacInnis, John Hopper. Causal Relationships and Familial Aggregation of Mammogram Risk Scores: Insights from Breast Cancer in Twins and Families [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-06.

Abstract PS03-09: Age-related normal breast tissue features differ in women with germline BRCA1/2 mutations

Abstract Ageing, a breast cancer risk factor, can be reflected in histologically normal breast tissue (NBT). However, the relationship between age-related histological features and cancer risk is not fully understood. We propose that biological and microscopic features can be identified in seemingly histologically NBT in gBRCA1/2m carriers that are indicative of the earliest tissue changes of breast cancer, potentially as a result of accelerated tissue ageing. To study NBT, we have put in place a unique and scalable repository, named OASIS, storing currently >2,000 digitised whole slide images (WSI) of H&E-stained NBT from individuals with long clinical follow-up. These tissues are from individuals with a spectrum of risk for developing breast cancer and derived from reduction surgery from non-gBRCA1/2m carriers, risk reducing masectomies, and from contralateral and peri-tumoural NBT from gBRCA1/2m carriers and women with breast cancer. Across 6 NBT resources, 70 selected WSIs were manually annotated for epithelial cells, fibrous stroma and adipocytes, resembling the "ground truth". Extensive comparisons of different tile sizes, tile overlapping ratios, stain normalisation techniques and deep learning (DL) feature extractors were conducted to implement a Tissue-Classifier, which achieved 95% accuracy in 3-fold cross-validation. Based on the MobileNet architecture, a DL-framework achieved a sensitivity of 81.2% and specificity of 81.8% (84.7% AUC) in predicting Tissue-Age based on discernible histological patterns in healthy women. In gBRCA1/2m carriers, we discovered features of accelerated tissue ageing (e.g. degree of lobule involution), indicating that the biological NBT age differs from their chronological age. Our DL-based framework robustly captured histological patterns to predict tissue components and age. The global organisation of these patterns showed variations in WSIs of women with different risks of developing breast cancers, which may provide new insights into premalignant alterations in NBT. Citation Format: Anita Grigoriadis, Mario Parreno-Centeno, Siyuan Chen, Gregory Verghese, Esther Lips, Cheryl Gillett, Louise Jones, Sarah Pinder. Age-related normal breast tissue features differ in women with germline BRCA1/2 mutations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS03-09.

Abstract PO3-09-03: Dysbiosis of gut microbiota in patients with breast cancer

Abstract [Background] The effects of gut microbiome on various diseases have become widely known, and many studies reported that there was a correlation between the change of gut microbiota, that is dysbiosis, and the progression of digestive tract cancer. In addition, it is well-known that gut microbiota was correlated to the efficacy of immune checkpoint inhibitors for multiple types of cancer. However, the significance of gut microbiota in patients with breast cancer still remains unclear. The aim of this study is to analyze the gut microbiota in patients with breast cancer, compared with healthy women. [Subjects and Methods] We used the pre-treatment feces of 79 patients with primary breast cancer who received treatment at our facility and performed metagenome analysis of the V3-4 region of 16S rDNA. We also analyzed the breast cancer patients' microbiota with QIIME2 analysis method, compared to randomly selected 100 women aged 30-77 years from NIBIOHN's public data . We also assessed the characteristics of the gut microbiota of breast cancer patients by subtypes and its relationship with clinical and pathological factors. [Results] In Japanese gut microbiota, the Firmicutes and Bacteroidetes phyla make up the majority, but Firmicutes was the most common bacterial phylum in 52% of the public cohort, whereas 96.2% (76/79) of the breast cancer patients’ group (BC) showed a significantly higher proportion (p< 0.0001). In addition, ANCOM analysis revealed that the relative bacterial amounts of the Firmicutes, Bacteroidetes, and Proteobacteria phyla were significantly decreased in BC compared to the public cohort (PC), and at the bacterial genus level, the Feacalibacterium genus was significantly decreased in BC. Furthermore, the percentage of Fusobacteria phylum, which is a well-known oral bacteria that exacerbates digestive tract cancer, was 49.3% in BC, compared to 35% in PC (p=0.04). Among BC, the relative frequency of Fusobacteria phylum was significantly higher in the HER2-negative group than in the HER2-positive group (p< 0.0001). In BC, both alpha diversity (p< 0.0001) and beta diversity (p=0.001) were significantly lower than in PC. [Conclusion] An increase in the Firmicutes phylum is known to be associated with obesity, and also likely to affect the incidence risk of breast cancer. The results suggest that the Fusobacteria phylum and Feacalibacterium genus may be risk or preventive factors for breast cancer. Dysbiosis of gut microbiota is suggested to be associated with various diseases, and in this study the decrease in bacterial amount and diversity was observed in BC compared to PC, which may affect the onset and progression of breast cancer. Citation Format: Mai Yamada, Takafumi Morisaki, Yo Sato, Kimihisa Mizoguchi, Yuka Takao, Yurina Ochiai, Yoshiki Ootubo, Saori Hayashi, Masafumi Nakamura, Makoto Kubo. Dysbiosis of gut microbiota in patients with breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-03.

Abstract PO5-18-06: On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy

Abstract Progranulin (PGRN/GP88) is an 88 kDa glycoprotein characterized by seven and a half double cysteine rich repeats which is the largest member of the granulin-epithelin protein family. PGRN/GP88 has been demonstrated as a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC), lung prostate, ovarian and digestive cancers. PGRN/GP88 tissue expression is an independent prognostic factor of recurrence in breast, lung cancers while elevated serum PGRN/GP88 level in metastatic breast, lung, ovarian and prostate cancer patients. Elevated PGRN/GP88 levels are associated with poor outcomes such as progression and shortened survival. An anti-human PGRN/GP88 monoclonal antibody able to inhibit the the in vitro and in vivo action of human PGRN/GP88 has been developed, chimerized and expressed in CHO cells. All IND enabling activities including pharmacology, GMP manufacturing, formulation and GLP toxicology studies have been conducted. The IND application has been filed and cleared by the Food and Drug Administration. A first-in-human, first-in-class phase 1 safety and efficacy clinical study of AG01 in patients with solid tumors and advanced disease with special focus on patients with breast, lung and ovarian cancers has been initiated and is on-going at the University of Maryland Greenebaum Cancer Center. The trial is registered as NCT05627960 to clinicaltrials.gov site. The presentation will provide an update on the number of patients enrolled in this on-going phase 1A trial. Supported by grants R44CA162629 and R44CA224718 from the National Cancer Institute to GS. Citation Format: Katherine Tkaczuk, Paula Rosenblatt, Ranee Mehra, Katherine Scilla, Nancy Tait, Binbin Yue, Ginette Serrero. On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-06.

Abstract PO1-02-13: Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA)

Abstract Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA) Background: There is accumulating evidence that the RANK/RANKL signaling pathway plays a pivotal role in breast tumorigenesis, particularly in the development of BRCA1-mutated tumors. Targeting the RANK pathway has been shown to attenuate breast cancer (BC) proliferation in vitro and in vivo. Studies using bone modifying agents as adjuvant therapy showed reduced rates of bone metastases and improved BC survival, as well as prevention of treatment-induced skeletal events. The GeparX clinical trial assessed the use of denosumab in patients with primary BC as an adjunct to neoadjuvant chemotherapy for its ability to enhance pathological complete response (pCR) rate and improve outcome. The trial randomized 780 patients twice to a total of 4 treatment groups (to receive or not receive denosumab; to receive nab-paclitaxel 125 mg/m2 weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles, both followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m2 every 2 weeks/every 3 weeks according to the investigator´s choice). Carboplatin was given in triple-negative breast cancer (TNBC), and trastuzumab biosimilar ABP980 plus pertuzumab was given in human epidermal growth factor-2-positive (HER2+) BC. Overall, the pCR (ypT0 ypN0) rate was 41% with denosumab vs 43% without; nab-paclitaxel at a dosage of 125 mg/m2 weekly resulted in a significantly higher pCR rate of 45% vs 39% with a dosage of 125 mg/m2 days 1 and 8 every 3 weeks. Research question: Does the germline mutation status of BRCA1/2 and other BC predisposition genes affect treatment outcome in the GeparX study? Methods: Genetic germline analyses assessing pathogenic variants in BRCA1/2 and 16 other BC predisposition genes were performed at the Center for Familial Breast and Ovarian Cancer, Cologne, Germany; 767 patients were included in this secondary investigation (308 TNBC, 306 HER2-/hormone receptor positive [HR+], 153 HER2+). Findings: Germline BRCA1/2 mutations were present in 91/767 patients (11.9%), with a higher mutation prevalence in TNBC (50/308, 16.2%) and HER2-/HR+ BC (37/306, 12.1%), and a low mutation prevalence in HER2+ BC (4/153, 2.6%). Overall, the pCR rate (ypT0 ypN0) was elevated in BRCA1/2 mutation carriers vs non-carriers (49.5% vs 41.1%, respectively; overall: OR 1.40, 95% CI 0.90-2.17; TNBC: OR 1.24, 95% CI 0.67-2.32; HER2-/HR+: OR 1.83, 95% CI 0.86-3.88). Highest pCR rates were observed in TNBC in BRCA1/2 mutation carriers vs non-carriers (60% vs. 54.7%, respectively). Highest pCR rate differences were observed HER2-/HR+ BC in BRCA1/2 mutation carriers vs non-carriers (32.4% vs. 20.8%, respectively). Regarding treatment arms, both BRCA1/2 mutation carriers and non-carriers benefitted most from nab-paclitaxel at a dosage of 125 mg/m2 weekly vs 125 mg/m2 days 1 and 8 every 3 weeks (BRCA1/2 mutation carriers: 55.3% vs 43.2%, respectively; OR 1.63, 95% CI 0.71-3.73; non-carriers: 43.7% vs 38.6%, respectively; OR 1.24, 95% CI 0.91-1.68). No beneficial effect was observed for denosumab vs no denosumab (51.1% vs 47.8% for BRCA1/2 mutation carriers, respectively; OR 1.14, 95% CI 0.50-2.60; 40.3% vs 41.9% for non-carriers, respectively; OR 0.94, 95% CI 0.69-1.27). Of the 617 BRCA1/2-negative patients, 59 patients carried mutations in other BC predisposition genes which did not predict therapy response compared to patients without any mutation. Conclusions: Irrespective of the treatment arm, higher pCR rates were observed in BRCA1/2 mutations carriers vs non-carriers. Both BRCA1/2 mutation carriers and non-carriers benefitted most from weekly nab-paclitaxel. No pronounced effect was observed for denosumab in either group. Key words: GeparX, denosumab, BRCA1/2 germline mutations, therapy response Funding: GeparX was financially supported by Amgen and BMS (Celgene). Citation Format: Rita K. Schmutzler, Theresa Link, Eric Hahnen, Mattea Reinisch, Jan Hauke, Marianne Just, Michael Untch, Corinna Ernst, Oliver Stötzer, Peter A. Fasching, Mohamad Kayali, Pauline Wimberger, Andreas Schneeweiss, Sandra Schmidt, Sabine Seiler, Christian Jackisch, Marc Thill, Kerstin Rhiem, Carsten Denkert, Valentina Nekljudova, Johannes Holtschmidt, Jens-Uwe Blohmer, Sibylle Loibl. Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-13.

Abstract PO4-11-08: Risk of second malignancies in breast cancer patients. A population-based retrospective cohort study between 2010-2020

Abstract Introduction: Breast cancer survivors live longer due to early detection programs and therapeutic advances. Staging and molecular classification are important for prognosis and treatment. At the same time these patients are at increased risk for second primary cancers. Comprehensive evaluation of second cancer risk among patients treated in recent decade with early detection and prevention programs of other tumors lacking. This study aims to identify, characterize and associate breast cancers with second primary malignancies based on different variables. Methods: We identified 3487 females with a first primary breast cancer between 2010 and 2020 in medical records at University Hospital of A Coruña in Spain. Over a median follow-up of 8 years, one hundred patients (2,9%) develop second cancer. According National Cancer Institute, second primary tumor (SPT) was defined as an invasive primary cancer after a first primary cancer. In our case a breast carcinoma. Second cancer risk was evaluated for all cancers (excluding ipsilateral breast carcinoma) which were diagnosed at least 12 months after primary breast tumor. We analyzed breast cancer subtype, family history and pathogenic genetic variants, tobacco use and second primary tumor type. Results: Several clinical characteristics were evaluated, including breast cancer stage, histological type and subtype. The incidence of breast cancer and SPT was increased with age with peaks in the 60’s and 70’s, respectively. Only 13% had SPT between 40-49 years. Approximately 10 women a year, in our study, developed second cancer. 52% of SPT patients had cancer family history. Pathogenic variant study was carried in 25% of women with SPT, 46% of them no mutation were found, but in 17% was detected a germline BRCA1 deleterious variant. Other pathogenic variants were founded: 4% in BRCA2, and 33% in others genes (CHEK2, MSH2, MSH6, PMS2, CDH1, FANC1 y SMAD4) Regards tobacco use, active smokers were 13% and 12% of women had been smoking years ago. Of these 13 active smokers, 10 develop lung cancer (77%) an 5 of former smokers (42%). Luminal subtype was the most common breast cancer (33% Luminal A, 34% Luminal B Her2 negative, 10% Luminal B Her2 positive, 4% Her2-enriched, 10% Triple negative and 3% carcinoma in situ with estrogen and progesterone expression) and stage I and II were most frequent (80%). The most usual second primary neoplasms were lung, colorectal and pancreatic carcinoma (21%, 17% and 7% respectively), and only 2% contralateral breast cancer, with an average of approximately 4 years between breast cancer and the SPT. In 11% of patients were found more than 2 tumors. At the time of the analysis, 73% of these patients are free of disease. In SPT study population few recurrences were described, 2 relapses of breast cancer and 9 of SPT. The median between breast cancer diagnosis and the SPT diagnosis was 54 months [0,7 – 129]. The median to relapse of breast cancer was 73 months [68 – 77]. The median between SPT diagnosis and relapse was 39,25 months [1 - 134]. STP recurrences were observed in colorectal and lung cancer, mainly. Data on recurrences and mutations were not significative. Conclusion: In our breast cancer population the incidence of second primary tumors is around 3% over a 10 – year period. The diagnosis of the SPT arises several years after breast cancer and generally has a worse prognosis. Elevated risks of second cancer among breast cancer survivors treated in recent decade suggests that heightened surveillance is warranted and continued efforts to reduce second cancers are needed. It is mandatory make an effort and focusing in recommendations and advise about tobacco consumption, healthy lifestyle and adherence to Pap test and stool test in survivors. Citation Format: Guadalupe Rama, Maria-Eva Perez-Lopez, Silvia Antolin Novoa, Cristina Reboredo, Beatriz Alonso, Sofia Silva Diaz, Begoña Graña, Lourdes Calvo, Tomas Garcia-Caballero. Risk of second malignancies in breast cancer patients. A population-based retrospective cohort study between 2010-2020 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-11-08.

Abstract PO4-15-02: ApoE polymorphism is associated with aggressive tumor phenotypes for breast cancer patients

Abstract Introduction: Apolipoprotein E (APOE) is implicated in several biological processes, such as protein synthesis, cell growth and differentiation, cholesterol transport, lipid metabolism, and tissue repair. APOE has different isoforms (E2, E3, and E4) that combine conflicting relations with cancer risk. This study aimed to evaluate the distribution of different isoforms of APOE among suspected HBOC (Hereditary Breast and Ovarian Cancer Syndrome) patients. Methodology: DNA was extracted from the blood cells of 108 patients. The detection was performed using qPCR after amplifying specific regions containing the polymorphisms. It was considered that all the amplicons containing Cq amplification < 35. The melting curve for each patient was analyzed to determine the frequency of the isoforms E2, E3, E4, and genotypes E2/E2, E2/E3, E2E4, E3/E3, and E3/E4. The allele and genotype were also correlated with hereditary variants previously identified by genetic tests for germline mutations and with tumoral phenotype. The data were expressed in frequency and associated using chi-square tests or Fisher's exact test (SPSS v20.0, p< 0.05). Results A total of 108 patients filling criteria for HBOC syndrome were evaluated. Among them, 15 (13.9%) had a mutation in BRCA1, 5 (4.6%) in BRCA2, and 2 (1.9%) in TP53. Most patients were under 45 years old (n=76, 70.4%), female (n=104, 96.3%), had a high school education (n=44, 44.0%), were non-smokers (n=79, 80.6%) or drinkers (n=76, 78.4%), and had no comorbidities (n=66, 64.1%). Overweight at diagnosis was observed in 61 (68.5%) individuals. The most frequent tumor phenotype and stage were luminal B (n=46, 43.4%) and stage IIIA (n=22, 26.2%), respectively. Neoadjuvant chemotherapy was performed in 40 (47.1%) with a high rate of complete and partial response 18 (36.7%) and 22 (44.9%), respectively. Regarding ApoE polymorphisms, the E2 allele showed the lowest frequency (n=7, 6.5%), E3 was present in 103 (95.4%) cases, while E4 was present in 39 (36.1%). The most frequent genotype was E3/E3 (n=64, 58.3%), followed by E3/E4 (n=34, 31.5%), E2/E3 (n=6, 5.6%), E4 (n=4, 3.7%), and E2/E4 (n=1, 0.9%). No cases of E2/E2 genotype were observed. The presence of E2 was inversely associated with comorbidity frequency (p=0.040) but directly associated with TP53 mutation (p=0.012) and triple-negative tumor phenotype (p=0.027). E3 was not associated with clinical characteristics, but E4 was associated with low Ki-67 immunoreactivity (p=0.033). The E2/E3 phenotype was directly associated with triple-negative tumors (p=0.044) and heterozygous tumors (p=0.011). Conclusion: The ApoE polymorphism, particularly the presence of the E2 allele in heterozygosity, is associated with TP53 mutation and a more aggressive tumor phenotype. Citation Format: Maria Claudia Luciano, Rosane Sant' Ana, Valeska Lima, Paulo Goberlanio Silva, Clarissa Albuquerquye, Flavio Bitencourt, Maria Julia Bezerra, Francisca Fernanda Oliveira, José Fernando De Moura, Isabelle Joyce Fernandes, Fernanda Leite. ApoE polymorphism is associated with aggressive tumor phenotypes for breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-02.

Abstract PO3-09-01: Integrating pathomic and radiomic images to classify risk of subsequent events among women with DCIS

Abstract Background Multiple sources of ~omic data can be generated from women at different stages of developing breast cancer, the leading cancer diagnosed in women worldwide. Traditionally interrogation of risk factors to study associations and develop prediction models for future breast events has been limited to one or few risk factors, or summary scores of clinical and tumor characteristics. Methods to bring mammography images and breast biopsies of precancer lesions together to summarize risk of cancer developing in the breast are urgently needed. Integration of these two sources has not been performed to date, but has potential to increase accuracy of risk prediction. Approach The Repository of Archival Human Breast Tissue (RAHBT) was established in 2007 at Washington University School of Medicine (WUSM) and maintains biospecimens and medical record data of women treated with breast-conserving surgery (BCS) or mastectomy for breast cancer at WUSM and six other St Louis metropolitan hospitals between 1981-2016. Prospective follow-up of cases is achieved through health records and Siteman tumor registry. Among 1831 patients with pathologically confirmed DCIS who had no prior cancer, 174 developed breast events at least six months after initial DCIS diagnosis. For each case diagnosed between January 1998 and March 2016 with subsequent breast events, two DCIS controls were matched on race, year of diagnosis (±5 years), age (±5 years), and type of surgery. Tissue micro arrays (TMAs) are constructed after breast pathology review and processed for H&E and imaged. Breast cancer risk factor data are uniformly retrieved form the medical records at time of processing cases of DCIS. Mammogram images are retrieved for all women. Full-field digital mammograms (FFDM) are all using the same technology (Hologic). Risk factors and outcome variables: ipsilateral breast events (IBE) was defined as the development of invasive cancer or DCIS in the treated breast at least 6 months post-diagnosis. Follow-up time was calculated from the date of DCIS diagnosis to the date of first IBE, death, or last follow-up, whichever occurred first. The predictors included commonly used clinicopathological factors: age, tumor grade (high vs. low/intermediate), comedonecrosis, surgical margins (close (≤2mm) vs. negative ( >2mm)), local treatment (BCS only and mastectomy vs. BCS+radiation), and endocrine therapy. BMI, menopausal status, and ER were also available for evaluation as predictors. We limited this analysis to women with digital mammograms immediately prior to diagnosis and include 128 cases and controls. Validation cohort As the RAHBT cohort continues to be followed additional second breast events have been documented after the cut off for events identified through March 2016, and the identical procedures used to review/confirm DCIS and subsequent breast events, construct TMAs, process H&E and images, and assemble risk factor data, and the associated digital mammograms. We have 13 additional ipsilateral breast events with complete data and their controls for independently testing the model performance. Statistical methods Propose novel supervised learning approach to integrate image data from mammograms and TMA slides that accommodates agreement between multi-omics. Results 128 (cases and controls, 21.9% ipsilateral subsequent events) identified for development and internal cross validation. Median age at diagnosis was 52 and median time to subsequent breast event was 63 mo. Controlling for the clinical/pathologic risk factors (age, BMI, BI-RADs density, treatment, tumor grade, parous, menopausal status, ER status, and race) and integrating the whole mammogram and TMA pathology images, we observe a 5-yr ipsilateral AUC = 0.74; 10-yr AUC 0.75. The independent validation is ongoing. Conclusions Integrating heterogeneous multiomic data sources can generate significant improvement in long term risk prediction after initial DCIS diagnosis. Citation Format: Shih-Ting Huang, Debbie Bennett, Robert West, Graham Colditz, Shu Jiang. Integrating pathomic and radiomic images to classify risk of subsequent events among women with DCIS [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-01.

Abstract PO5-07-06: Impact of patient-specific factors on quantitative breast parenchymal texture features

Abstract Breast parenchymal texture characterizes the spatial and structural patterns of breast tissue and is an independent predictor of breast cancer risk. Although it has conceptual similarities with another breast composition measure, breast density, parenchymal texture is more complex and is represented by multiple quantitative measures. The extent to which the epidemiology and biological basis of parenchymal texture and breast density differ has not been well described. In this cross-sectional study, we evaluated quantitative measures of parenchymal texture among 308 postmenopausal women aged ≥ 45 years who participated in a routine breast cancer screening at an academic medical center between 2020 and 2022. After providing informed consent, participants completed a short interview-based questionnaire. Additional demographic and breast cancer risk factor information was obtained from the medical record. Parenchymal texture features were measured from craniocaudal views of full-field digital mammograms. Measured texture values were standardized and averaged across left and right breasts. For this analysis, we evaluated associations between features previously validated as being associated with breast cancer risk (fractal dimension, grey-level mean, co-occurrence entropy and inverse difference moment) and patient personal and clinical characteristics reported at the time of screening. Associations between texture features and participant characteristics were evaluated using Pearson correlations (continuous variables) or the Kruskal-Wallis test (categorical variables). Generalized linear models were used to adjust for technical factors associated with image acquisition, including mammography machine, compression force, and software version. P-values less than 0.05 were considered statistically significant. Among the 308 participants, 70% were White, 24% were Black, 1% were Asian, 1% were American Indian, and 4% were another race that was not specified. 4% of participants reported Hispanic ethnicity. The mean age was 64.7 years (range 45 – 84 years). Fewer than half of the women were reported by a radiologist to have dense breasts (heterogeneously dense – 24%, extremely dense – 5%, vs. almost entirely fatty – 21%, scattered fibroglandular densities – 50%). The mean body mass index (BMI) was 29.4 kg/m2 (range 19.4 to 53.1 kg/m2) and 77% of the women were parous. BMI was strongly correlated with fractal dimension (r=0.62, P< 0.01) and grey-level mean (r=-0.48, P< 0.01), and had a weaker correlation with co-occurrence entropy (r=-0.19, P< 0.01). Age was weakly correlated with co-occurrence inverse difference moment (r=-0.12, P=0.03). BI-RADS breast density was inversely associated with fractal dimension, grey-level mean, and co-occurrence entropy (all P< 0.01). Adjustment for technical factors attenuated some associations, but BMI associations with fractal dimension (P< 0.01) and gray-level mean (P< 0.01), and breast density associations with fractal dimension, grey-level mean, and co-occurrence entropy (all P< 0.01) all remained statistically significant. Parity was not associated with any of the features evaluated in unadjusted or adjusted analyses (all P >0.05). These data suggest that, in postmenopausal women, risk-associated parenchymal texture features are associated with measures affected by body size and adiposity, but not with measures related to age or reproductive status. Longitudinal studies are needed to understand the temporality of these associations. Additionally, future studies will address the joint effects of texture features and the impact of endogenous estrogen levels on the features, which will provide insight into the biological mechanisms that influence texture feature associations with personal characteristics and breast cancer risk. Citation Format: Sarah Nyante, Yukie Kajita, Walter Mankowski, Ley Killeya, Despina Kontos, Xianming Tan, Eric Cohen, Cherie Kuzmiak. Impact of patient-specific factors on quantitative breast parenchymal texture features [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-07-06.

Abstract PO5-14-01: Weight loss and omega-3 polyunsaturated fatty acid intervention in overweight and obese peri- and postmenopausal women with increased breast cancer risk modifies the gut microbiome and is associated with circulating biomarkers

Abstract Background: Obesity-associated gut microbiome dysbiosis is thought to increase risk for postmenopausal breast cancer through alteration of estrogen metabolism and an increase in pro-inflammatory microbe abundance. Many studies have reported an increase in the Firmicutes/Bacteroidetes phyla ratio as a biomarker of obesity and is associated with adverse metabolic outcomes. Marine omega-3 eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids are thought to have favorable metabolic and inflammation resolving properties resulting in reduced risk for several epithelial cancers. One possible mechanism is the effect of EPA and DHA on the gut microbiome. We assessed the effect of weight loss and/or omega-3 supplementation on the gut microbiome and circulating molecular breast cancer risk factors. Methods: 46 peri/postmenopausal overweight and obese women at increased risk for breast cancer were enrolled into a weight-loss intervention and after 2 weeks randomized to 3.25 g/day combined EPA and DHA or placebo (PMC8416797). Fecal samples were collected at 0, 2-weeks and 6-months, with matched fecal samples for all timepoints available for 26 patients. Fecal samples at 6-months were available for 34 patients. 12M read depth metagenomic sequencing was performed on DNA isolated from feces to determine shifts in the gut microbiome. Fasting and non-fasting blood was also collected for circulating biomarker analysis. Body composition by DXA scan were also performed at baseline and 6-month time points. Results: Mean baseline BMI was 32 kg/m2. There was no significant difference between arms in age, baseline BMI, % body fat, or baseline Firmicutes/Bacteroidetes ratio. We identified gut microbiota species (A. hadrus and P. faecium) that correlated with metabolic parameters (% body fat, adiponectin/leptin ratio, and fasting insulin), species (P. dorei and B. ovatus) that correlated with estradiol levels, and mucin-degrading species (D. formicigenerans and R. gnavus) whose abundance correlated with inflammation (as measured by circulating monocyte-chemoattractant protein 1 (MCP-1)). Median 6-month weight change for all randomized subjects was -10% from baseline. Favorable change in the Firmicutes/Bacteroidetes ratio was associated both with the degree of weight loss and with omega-3 supplementation, although significant species modification differed between weight loss and omega-3 PUFA groups. Women with both >10% weight loss and omega-3 supplementation had a significantly reduced Firmicutes abundance and lower Firmicute/Bacteroidetes ratio than other groups. Species abundance shifts appear to differ between weight loss and omega-3 supplementation with 3 species modified by weight loss and 12 species shifted by omega-3 PUFA administration. Omega-3 PUFA supplementation significantly reduced proportional abundance of Dorea formicigenerans, which was a microbe associated with inflammation. Conclusions: Omega-3 supplementation at 3.25 g/day compared to placebo had a greater net effect on changing the gut microbiome in overweight and obese women at increased risk for breast cancer undergoing a weight loss intervention. Change in the gut microbiome may serve as a useful response biomarker in Phase II prevention trials of omega-3 fatty acid and weight loss. Citation Format: Katherine L. Cook, Erin Giles, Amy Kreutzjans, Shahid Umar, Christie Befort, Bruce Kimler, Stephen Hursting, Carol Fabian. Weight loss and omega-3 polyunsaturated fatty acid intervention in overweight and obese peri- and postmenopausal women with increased breast cancer risk modifies the gut microbiome and is associated with circulating biomarkers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-14-01.

Abstract PO4-19-02: Genetic risk estimation in breast cancer and assessing health disparities

Abstract Background: Breast Cancer (BC) incidence and the distribution of BC risk factors vary between racial and ethnic groups within the United States. It has been demonstrated that providing education on individualized breast cancer risk will improve patient uptake to recommended BC screening and prevention strategies. Most clinical risk assessment tools, including the validated IBIS model were derived from data using non-Hispanic white women. Consortia have also now identified over 300 common genetic susceptibility loci for BC, summarized by the polygenic risk score (PRS). When combined with clinical risk assessment tools, such as the IBIS or BCRAT models, the PRS can further refine risk estimation for patients. To date, most studies on the use of PRS have been done in non-Hispanic white women. While these PRS still perform well in racial minorities, there has been a recognized need to improve racial and ethnic diversity in genomic research cohorts. Herein, we aim to combine clinical risk assessment models that are already used in routine clinical practice with information derived from PRS testing in women of racial minorities to determine if this can improve risk estimation, patient understanding, and uptake to recommended breast cancer screening and prevention strategies. Design: This is a minimal risk prospective study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the information provided by the PRS influenced patient decisions regarding recommended BC screening and prevention. Patients will have IBIS and BCRAT risks calculated at baseline visit. A survey of patient perceptions/understanding of risk, intention to undergo screening, and use of preventive medicine is completed after baseline visit prior to receiving the PRS results. Blood sample is obtained at baseline and DNA samples are analyzed for approximately 300 SNPs on a custom-designed, targeted SNP panel from ThermoFisher Scientific by the Mayo Clinic Genomics Laboratory. This PRS result is then combined with the clinical risk assessments (IBIS and BCRAT scores) using the R package Individualized Coherent Absolute Risk Estimators (iCare) tool to provide a new estimate of breast cancer risk for 5year, 10year, and lifetime risk. Patients are seen for follow-up to review results and then complete a second survey to assess their understanding of the results, BC risk, and how the PRS impacted their decision to undergo screening/prevention strategies. Eligibility Criteria: Women who self-identify as African American/Black or Hispanic/Latinx between 30-75 years old with any of the following: 1.)IBIS score of ≥5% for the 10 year risk OR BCRAT score of ≥ 3 % for the 5 year risk. 2.) History of biopsy proven atypical hyperplasia 3.) History of biopsy proven lobular carcinoma in situ. Specific Aims: Aim 1: The primary aim of this study is to explore if the addition of PRS to the BCRAT and IBIS score will improve intentions to undergo recommended breast cancer screening strategies such as mammography, MRI, or molecular breast imaging in women of underserved racial minorities Aim 2: To explore if the addition of the PRS to the BCRAT and IBIS risk score will aid women of racial minorities in deciding whether to take preventative endocrine therapy. Aim 3: To understand how individualized risk assessment and information on PRS may alter perceived risk of breast cancer. Statistical Methods Analysis will be mostly descriptive. Continuous variables will be summarized as mean (standard deviation) or median (range) and categorical variables will be reported as frequency (percentage). Kaplan-Meier method will be used to estimate the long-term cumulative risk of cancer. Current Accrual: 3. Target Accrual: 50 Citation Format: Lauren Cornell, Sandhya Pruthi, Linda Hasadsri, Sarah McLaughlin. Genetic risk estimation in breast cancer and assessing health disparities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-02.