Breast Cancer Morbidity Research Articles

Identification of a novel immune checkpoint-related gene signature predicts prognosis and immunotherapy in breast cancer and experiment verification

Breast cancer (BRCA) is one of the pivotal causes of female death worldwide. And the morbidity and mortality of breast cancer have increased rapidly. Immune checkpoints are important to maintain immune tolerance and are regarded as important therapeutic targets. However, research for BRCA were limited to single immune checkpoint-related gene (ICG) and few studies have systematically explored expression profile of Immune checkpoint-related genes or attempted to construct a prognostic gene risk model based on immune checkpoint-related genes. We identified immune checkpoint-related differentially expressed genes (DEGs) in BRCA and normal breast tissues from TCGA database. A 7-gene signature was created by utilizing the univariate Cox regression model with least absolute shrinkage and selection operator (LASSO) Cox regression method. In addition, we conducted a nomogram to predict the prognostic significance. This tool enables quantitative prediction of patient prognosis, serving as a valuable reference for clinical decision-making, thereby improving patient outcomes. Relationships between our risk model and clinical indicators, TME (Tumor Microenvironment), immune cell infiltration, immune response and drug susceptibility were investigated. A set of in vitro cell assays was conducted to decipher the relationship between MAP2K6 and proliferation, invasion, migration, colony formation and apoptosis rate of breast cancer cells. As a result, we established a prognostic model composed of seven ICGs in BRCA. Based on the median risk score, BRCA patients were equally assigned into two groups of high- and low-risk. High-risk BRCA patients have poorer OS (overall survival) than low-risk patients. In addition, there were remarkable differences between these two groups in clinicopathological features, TME, immune cell infiltration, immune response and drug susceptibility. The results of GO and KEGG analyses indicated that DEGs between the high- and low-risk groups were involved in immune-related biological processes and pathways. GSEA analysis also showed that a number of immune-related pathways were notably enriched in the low-risk group. Finally, results of cell-based assays indicated that MAP2K6 may play a pivotal role in the initiation and progression of breast cancer as a tumor suppressor gene. In conclusion, we created a novel ICG signature that has the potential to predict the survival and drug sensitivity of BRCA patients. Furthermore, this study indicated that MAP2K6 may serve as a novel target for BRCA therapy.

BIOM-31. MOLECULAR ANALYSIS OF RESECTED BREAST CANCER BRAIN METASTASES REVEALS CEREBELLAR LOCATION AND TRIPLE NEGATIVE SUBTYPE ARE NEGATIVE PROGNOSTIC FACTORS

Abstract BACKGROUND Brain metastases (BMs) are a significant cause of morbidity and mortality in metastatic breast cancer (MBC), yet prognostic and predictive biomarkers remain poorly understood. STUDY DESIGN 90 consecutive patients with breast cancer BMs who underwent surgical resection from 2006-2022 were retrospectively identified. Review of the electronic medical record and institutional cancer registry were completed to identify baseline clinical parameters and outcomes. BM mutation analysis was performed using a CLIA-certified targeted DNA mutation sequencing assay as part of routine clinical care. RESULTS All patients were female, median age at first BM resection was 57.9 years (range 27.0-81.3 years), and receptor subtypes included HR+/HER2- (n=27, 30.0%), HER2+ (n=33, 36.7%), and triple negative BC (TNBC; n=30, 33.3%). At time of first BM resection, most patients had a solitary BM (n=55, 61.1%), with anatomic locations including cerebellar (n=29, 32.2%), frontal (n=26, 28.9%), and parietal (n=17, 18.9%) sites. BM DNA mutation analysis (n= 20) revealed pathogenic alterations in TP53 (n=17, 85.0%), ERBB2 amplification (n=7, 35.0%), PIK3CA (n=4, 20.0%), BRCA1 (n=3, 15.0%), and BRCA2 (n=2, 10.0%). Most patients received postoperative radiation (n=82, 90.8%) and/or systemic therapy (n=67, 82.7%). Cerebellar location was significantly associated with the risk of developing leptomeningeal disease compared to other BM resection sites (HR = 2.75, p=0.02). Among all patients, median overall survival (OS) from first BM resection was 27.8 months (range 0.1-196.6 months). HR+/HER2- (median 37 months) or HER2+ (median 36 months) MBC was associated with significantly increased OS compared to TNBC (14.4 months) (p<0.01, log-rank test). CONCLUSIONS Patients with breast cancer BMs exhibited a median OS of >2 years following BM resection, and patients with TNBC had a significantly worse prognosis. Targetable mutations were observed in 40% of resected BM specimens, supporting the utility of molecular analysis of resected BMs to help guide clinical management.

Long-term trends in the burden of breast cancer in China over three decades: a joinpoint regression and age-period-cohort analysis based on Global Burden of Disease 2021.

We analyzed the trends in breast cancer (BC) morbidity, prevalence, and mortality among Chinese residents from 1990 to 2021. We then used joinpoint regression to further assess BC morbidity and mortality. We screened the morbidity, mortality, and prevalence of BC in Chinese residents (1990-2021) from the Global Burden of Disease. We used age-period-cohort (APC) modeling to assess the effects of age, period, and cohort on BC morbidity and mortality separately. We also used the joinpoint model to characterize trends in BC morbidity and mortality in China. From 1990 to 2021, age-standardized rates of morbidity have risen significantly, whereas mortality has declined. We discovered that the risk of morbidity and death rose with age by using the APC model. We also found that mortality and morbidity roughly continued to increase over time, and finally, we found that the later the birth cohort, the lower the mortality and the higher the morbidity. From 1990 to 2021, the burden of BC disease in China will continue to rise, and the situation of BC prevention and control will remain severe. Therefore, regular imaging and palpation examinations should be performed in the regular population over 40 years of age. When treating patients with BC, healthcare workers should develop individualized treatment plans to further reduce mortality.

Breast cancer and its determinants in Ethiopia: a systematic review and meta-analysis.

Breast cancer is the leading cause of cancer morbidity and mortality among women. Still, there is a paucity of studies to know the magnitude of the problem in Ethiopia. Hence, this review was intended to pool the prevalence and identify the determinants of breast cancer in Ethiopia. A systematic review and meta-analysis was conducted. Databases like PubMed/MEDLINE, HINARI, Science Direct, and Google Scholar, as well as websites of organisationsI organizations,rewere searched between 25 February and 6 March 2023. All observational studies in Ethiopia that reported either the magnitude and/or determinants of breast cancer regardless of publication status were included. Two authors independently assessed and extracted the data. The Joanna Briggs Institute meta-analysis of statistics assessment and review instrument quality appraisal tool was used to assess the quality of the articles. Effect estimates were done by using the random-effects model. The meta-analysis results were displayed by using forest plots. Seventeen articles were reviewed with 24 435 total participants. The pooled proportion of breast cancer morbidity among patients with cancer was 20. 58% (95% CI 17.25%, 23.90%) in Ethiopia. Consuming packed foods (POR=2.12, 95% CI 1.41, 3.17), presence of high cholesterol (POR=4.08; 95% CI 2.75, 6.07), physical inactivity (POR=3.27; 95% CI 1.80, 5.94), high body mass index (BMI) (POR=2.27; 95% CI 0.85, 6.03), postmenopause (POR=2.25; 95% CI 1.63, 3.10), family history of cancer (POR=3.65; 95% CI 0.85, 15.71) and lack of breastfeeding (POR=2.76; 95% CI 0.90, 7.92) were the determinants of breast cancer. One of five patients with cancer is diagnosed with breast cancer in Ethiopia. Furthermore, more than a quarter of women with cancer suffer from breast cancer. Processed food consumption, high cholesterol in the body, lack of physical activity, high BMI, postmenopause, family history of cancer and lack of breastfeeding were the risk factors for breast cancer. The use of healthy food sources such as fruits and vegetables, and homegrown varieties of crops rather than seeking processed foods would help. CRD42023417733.

Breast cancer imaging-clinical experience with two-dimensional-shear wave elastography: A retrospective study.

Breast cancer morbidity has been increasing worldwide, but treatments are improving. The therapeutic response depends on the stage at which the disease is diagnosed. Therefore, early diagnosis has never been more essential for successful treatment and a reduction in mortality rates. Radiology plays a pivotal role in cancer detection, and advances in ultrasound (US) palpation have shown promising results for breast cancer imaging. The addition of two-dimensional-shear wave elastography (2D-SWE) US in the routine breast imaging exam can increase early cancer detection and promote better surveillance. To evaluate the clinical applications of 2D-SWE US in breast cancer detection and its combination with other imaging modalities. The 200 consecutive female patients aged 50-80 were examined to evaluate palpable breast lesions. All patients underwent mammography, bright mode (B-mode) US, and 2D-SWE followed by US-guided biopsy in two consecutive sessions. Combining B-mode and shear wave US imaging with X-ray mammography revealed 100% of the suspicious lesions, resulting in greater sensitivity, specificity, and negative predictive value. The result improves compared to either B-mode or 2D-SWE alone (P = 0.02). Combining 2D-SWE with conventional US and X-ray techniques improves the chance of early cancer detection. Including 2D-SWE in regular breast imaging routines can reduce the need for biopsies and improve the chance of early cancer detection and survivability with the proper line of therapy.

Spatial disparities in cancer incidence and mortality, indicating gaps in prevention and/or care

Abstract Background There is a rich literature on the distribution of cancer incidence and mortality in socioeconomically different regions of the world, but none of the studies has compared the spatial distribution of mortality and morbidity to see if they are consistent with each other. Methods All malignant neoplasms and separately by cervical, colorectal, breast, pancreatic, lung and oral cancers were studied in the Hungarian population aged 25-64 years for the period 2007-2018 at the municipality level by sex. In each case, the spatial distribution of morbidity and mortality and their clusters were compared with each other and with the level of deprivation using disease mapping, spatial regression, risk analysis and spatial scan statistics. Results All-cause cancer morbidity and mortality showed a significant association with deprivation. However, the slope of the increase in mortality with increasing deprivation was much steeper than for morbidity in both sexes. The association between deprivation and morbidity was not consistent across all cancers. No significant association was found for male colorectal cancer (RR: 1.003; 95%CI 0.986-1.019), pancreatic cancer (1.014; 95%CI 0.983-1.045) and female colorectal cancer morbidity (RR: 0.977; 95%CI 0.991-1.029), whereas a negative association was found for breast cancer morbidity (RR: 0.977; 95%CI 0.963-0.991). In contrast, a positive association between deprivation and mortality was found for each type of cancer, although with different RRs. However, disease mapping analyses showed only partial overlap between high-risk morbidity and mortality areas, often independent of deprivation. Conclusions Our results highlight not only the diverse relationship between the epidemiological situation and deprivation, but also the disproportionate relationship between cancer morbidity and mortality, thus identifying geographical regions and sub-regions with populations that require special public health attention. Key messages • Comparative spatial analysis of cancer morbidity and mortality at the municipality level is strongly recommended to identify populations in need of targeted cancer prevention and/or care. • The usefulness of comparative spatial analysis of cancer morbidity and mortality is demonstrated in Hungary, one of the countries with the most unfavourable cancer burden in international comparison.

Abstract A089: Intersecting burdens: The role of social barriers and perceived stress in moderating cortisol reactivity among African American breast cancer survivors

Abstract Background: Disparities in breast cancer morbidity and mortality persist in African Americans. Social determinants and their subsequent effect on stress reactivity may impact the biological mechanisms associated with the onset and progression of cancer. However, stress reactivity has not been examined specifically among African American breast cancer survivors. Objective: To evaluate within-subject variation in stress reactivity among African American breast cancer survivors and determine whether this reactivity is influenced by social stressors, such as financial strain and social isolation, known to be associated with cancer outcomes. Methods: We conducted a laboratory intervention study using the Trier Social Stress Test on African American breast cancer survivors. We measured stress reactivity using salivary cortisol levels; socioeconomic, social, and psychological stressors were estimated by self-report. We performed multi-level random effect repeated-measures linear regression models to estimate within-subject changes in cortisol levels. We tested the moderating effects of social factors and cumulative social stressors on reactivity outcomes. Results: Sixty African American breast cancer survivors were included in the study. There were significant increases in mean cortisol levels at 30 minutes (beta=0.054, 95%CI=0.026, 0.082; p<0.001) and 40 minutes (beta=0.040, 95% CI=0.015, 0.065; p=.002) post-stress during the recovery period. We identified significant interactions between time and social stressors on cortisol levels for financial strain (χ2/df=15.83/4, p=.003), social isolation (χ2/df=9.67/4, p=.04), negative life events (χ2/df=12.75/4, p=.01), perceived stress (χ2/df=11.93/4, p=.02), and cumulative index of social stressors (χ2/df=11.14/4, p=.03). Conclusion: Social risk factors moderate the effects of stressors on cortisol reactivity among African American breast cancer survivors. There is a need to understand the lived experiences of Black women and develop interventions that mitigate the impact of social stressors on stress responses. Citation Format: Dr. Fatimata Sanogo, Dr. Junhan Cho, Dr. Trista Beard, Dr. Chanita Hughes Halbert. Intersecting burdens: The role of social barriers and perceived stress in moderating cortisol reactivity among African American breast cancer survivors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A089.

Abstract B134: Socioeconomic, social, and clinical factors associated with loneliness among African American breast cancer survivors

Abstract Importance: Social connections are an important driver of cancer risk and outcomes and animal studies have shown that social isolation is important to breast cancer initiation and progression. However, limited empirical data are available on perceived loneliness among patient groups who are at increased risk for breast cancer morbidity and mortality. Objectives: The purpose of this study was to characterize the nature and distribution of loneliness in a sample of African American breast cancer patients and identify clinical and social factors having significant independent associations with perceived loneliness among these survivors. Methods: The study included African American breast cancer patients (n=110) who provided self-reported data on loneliness as part of a participating in a prospective observational study and randomized trial that examined stress reactivity using the Trier Social Stress Test. Loneliness was measured using a short form of the Loneliness Scale; scores were dichotomized using the median split to characterize patients as experiencing high versus low levels of loneliness. Multivariate logistic regression analysis was used to identify factors having significant associations with loneliness. Results: Over half (51.82%) of patients reported experiencing high levels of loneliness. Clinical and social factors that had significant independent associations with loneliness included marital status (OR=2.853, CI=1.066, 7.635, p=0.037), financial strain (OR=3.240, CI=1.114, 9.422, p=0.031), and the number of co-morbidities. Compared to patients who did not have any co- morbidities, those who had one, two, or three or more comorbidities had seven (CI=1.066, 40.645; p=0.029), eleven (CI=1.858, 66.716, p=0.008), and eleven (CI=1.757, 65.244; p=0.010) times the odds, respectively, of experiencing loneliness. Conclusions and Relevance: Many African American breast cancer patients in this study reported high levels of loneliness. Greater efforts are needed to identify patients who may benefit from interventions that enhance social connections, especially if they are married, experiencing financial strain, and have co-morbid conditions. Citation Format: Kelsie Campbell, Fatimata Sanogo, Trista Beard, Melanie Jefferson, Bodhour Sahlia, Chanita Hughes Halbert. Socioeconomic, social, and clinical factors associated with loneliness among African American breast cancer survivors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B134.

Social and clinical drivers of stress responses in African American breast cancer survivors

Racial differences in breast cancer morbidity and mortality have been examined between Black/African American women and White women as part of efforts to characterize multilevel drivers of disease risk and outcomes. Current models of cancer disparities recognize the significance of physiological stress responses, yet data on stress hormones in Black/African American women with breast cancer and their social risk factors are limited. We examined cortisol levels in Black/African American breast cancer patients and tested their association with social and clinical factors to understand the relationship between stress responses and women’s lived experiences. Seventy-two patients who completed primary surgical treatment were included in this cross-sectional study. Data on sociodemographic characteristics and chronic diseases were obtained by self-report. Breast cancer stage and diagnosis date were abstracted from electronic health records. Cortisol levels were determined from saliva samples. Compared to those without hypertension, patients with hypertension were 6.84 (95% CI 1.33, 35.0) times as likely to have high cortisol (p = 0.02). The odds of having high cortisol increased by 1.42 (95% CI 1.03, 1.95, p = 0.03) times for every point increase in negative life events. Hypertension and negative life events are associated with high cortisol levels in Black/African American patients. These findings illustrate the importance of understanding the lived experiences of these patients to enhance cancer health equity.

Features of the incidence of breast cancer in the Republic of Kazakhstan

Aim of the study. Analysis of breast cancer incidence in Kazakhstan for the period 2020 – 2022.Materials and methods. The study included all registered cases of breast cancer morbidity and mortality in the Republic of Kazakhstan for the period 2020-2022. Data for analysis were taken from the official statistical source: Statistical collection «Health of the population of the Republic of Kazakhstan and the activities of healthcare organizations in 2020»; Statistical collection “Health of the population of the Republic of Kazakhstan and the activities of healthcare organizations in 2021-2022.” The search depth was 3 years, from 2020 to 2022. A direct standardization method using a global population standard was used to calculate standardized morbidity and mortality rates.Results and discussion. As a result of studying statistical data for 2020-2022, it was found that cancer incidence rates per 100 thousand population in 2022, compared with 2021, increased by 5.2%, and compared to 2020 increased by 13.5%. In the structure of incidence, both in 2020 and 2021, and in 2022, breast cancer occupied 1st place, with an increase in dynamics from 2020 to 2022 from 8.76 to 9.73 per 100 thousand population.An analysis of the incidence of breast cancer by stages of the disease in the context of regions of Kazakhstan showed that high rates of stages I and II of breast cancer were established in the Kyzylorda, Pavlodar, and Atyrau regions. The lowest incidence rates of stage I and II breast cancer were observed in Akmola, Mangistau and Turkestan regions.Conclusions. According to the results of our review, many studies indicate that this disease continues to be the most frequently diagnosed malignant neoplasm and the leading cause of death among women in various countries of the world, including Kazakhstan. The conclusion of this article is that the incidence and mortality from breast cancer continues to be an urgent epidemiological problem in Kazakhstan, requiring further scientific research to identify risk factors.

The current landscape of coumarin hybrids with antibreast cancer therapeutic applications: An updated review.

Globally, breast cancer (BC) has the highest prevalence among malignant diseases. BC is also the primary cause of death among women. Notably, BC morbidity has been increasing continuously at an approximate growth rate of 2.2% per year. Persistent BC is a major public health issue worldwide. Consequently, novel chemotherapeutic agents to combat this lethal disease should be developed urgently. Coumarins with interesting structural and mechanistic variations exhibit promising activity in several forms of BC, including BCs with multidrug resistance. In particular, coumarin hybrids composed of coumarin and one or more anti-BC pharmacophores can target different biological components in BC cells simultaneously. Thus, coumarin hybrids are useful scaffolds that can help improve the anti-BC efficacy of coumarins, reduce side effects, improve pharmacokinetics, minimize drug-drug interactions, and circumvent drug resistance. This review, in which articles published from 2020 to the present day have been evaluated, highlights the landscape of coumarin hybrids that exhibit therapeutic effects against breast cancer. These findings can aid further investigations on novel antibreast-cancer therapeutics.

Abstract PO3-19-03: Addressing USPSTF 2023 Identified Key Gaps in Knowledge in Breast Cancer Screening through TMIST (ECOG-ACRIN EA1151) or its Ancillary Studies

Abstract Background The United States Preventative Services Task Force in their 2023 recommendations identified areas where more research data is needed to inform future breast cancer screening recommendations. Research areas identified are: improve clinicians and patients understanding and evaluation of dense breast tissue on a screening mammogram, benefits and harms of supplemental screening using ultrasound or MRI for women with dense breasts, health outcomes such as rates of breast cancer diagnosis requiring treatment, rates of advanced breast cancers diagnosed across consecutive screening rounds, and breast cancer-associated morbidity and mortality, causes of increased risk of breast cancer mortality in black women across spectrum of stages and biomarker patterns, understand why black women are more likely to be diagnosed with breast cancers that have biomarker patterns that are indicative of poor health outcomes, assess benefits/harms differences between annual and biennial screening for breast cancer in women overall and if there are differences between black and white women, approaches to reduce the risk of overdiagnosis leading to overtreatment of breast lesions found at screening that may not cause morbidity and mortality, natural history of DCIS, and identify prognostic indicators of breast tumors that are unlikely to affect quality or length of life. Methods The ongoing TMIST study, currently with 88,801 asymptomatic women presenting for screening mammography ages 45-74 enrolled out of 128,905, could contribute to scientific evidence to support the above research areas through existing study aims and planned ancillary studies. Supplemental Screening with US and MRI: TMIST PreSCRIB will utilize Machine Learning applied to TMIST and All of Us data, including genetics, mammograms, social determinates of health and other data to recommend individualized screening strategies for women. DxMRI is a study where women will get AbMRI at time of Dx work-up. There are plans to use these examinations plus supplemental screening MRIs performed on TMIST subjects in an enriched reader study to evaluate the role of supplemental screening MRI in moderate risk women. Rates of breast cancer treatment, consecutive screening, morbidity, and mortality: TMIST’s primary outcome is the proportion of women experiencing an advanced breast cancer and needing treatment. TMIST is also collecting information on health care utilization following a cancer diagnosis, including types of treatment given, and costs data from the screening and diagnostic work-up visits, and mortality data for study participants. Increased risk of breast cancer mortality in black women: TMIST is performing PAM50 plus p53 status, immune profile, DNA repair phenotype, and 21-gene recurrence assay on all breast cancers and a subset of benign tissue. Blood and buccal smears might also help address this issue. Ongoing work, funded by the Susan B. Komen Foundation, focuses on improving Black participation in TMIST Biorepository (currently about 45% participation of the 21% of TMIST US black subjects). Surveys are planned on perceived racism and social determinates of health as part of DxMRI Study. Screening Frequency: We are developing a collaboration with the UK-based clinical trial PROSPECTS to compare rates of all cancers and advanced cancers for annual, biennial, and 3-year screening. Overdiagnosis, natural history of DCIS, prognostic indicators of breast tumors not impacting quality of life: PRoGram- will use radiomics, genomics and pathomics to develop a greater understanding of the variability of the non-advanced cancers diagnosed in the TMIST population, including DCIS. It is hoped that this model will provide greater understanding of the risk of poor outcomes for women diagnosed with lower risk cancers, including DCIS. Citation Format: Etta Pisano, Constantine Gatsonis, Mitchell Schnall, Melissa Troester, Elodia Cole, Jean Cormack, Ilana Gareen, Martin Yaffe, Laura Collins, Amarinthia Curtis, Ruth Carlos, Kathy Miller, Christopher Comstock. Addressing USPSTF 2023 Identified Key Gaps in Knowledge in Breast Cancer Screening through TMIST (ECOG-ACRIN EA1151) or its Ancillary Studies [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 PO3-19-03.

Concurrent factors associated with adherence to adjuvant endocrine therapy among women with non-metastatic breast cancer.

Adjuvant endocrine therapy (AET) reduces breast cancer morbidity and mortality, yet women often report suboptimal adherence. Though correlates of AET adherence are well-documented, few studies examine the relative importance of multi-level factors associated with adherence. The aim of this study was to identify factors most strongly associated with AET adherence in women with breast cancer. Between 10/2019 and 6/2021, women (N = 100) with non-metastatic, hormone receptor-positive breast cancer, taking AET who reported AET-related distress enrolled into a clinical trial. Participants completed baseline measures, including the Medication Adherence Rating Scale-5, sociodemographics, and validated measures of anxiety, depression, medication-taking self-efficacy, social support, and treatment satisfaction. We created a latent factor and tested associations between sociodemographic, medical, and psychosocial characteristics and adherence. Associated predictors (p < .10) were entered into a structural model, which was corroborated via multivariate regression modeling. A four-indicator latent adherence factor demonstrated good model fit. Participants (Mage = 56.1years, 91% White) who were unemployed (B = 0.27, SE = 0.13, p = .046) and reported greater treatment convenience (B = 0.01, SE = 0.01, p = .046) reported greater adherence. Scores of participants who reported greater medication-taking self-efficacy (p = .097) and social support (p = .062) approached better adherence. Greater medication-taking self-efficacy (B = 0.08, SE = 0.02, p < .001) and being unemployed (B = 0.28, SE = .14, p = .042) were most strongly associated with greater adherence, independent of other predictors. Multivariate modeling confirmed similar findings. Medication-taking self-efficacy and employment status were associated with AET adherence above other related factors. Enhancing patients' confidence in their ability to take AET for breast cancer may represent an important intervention target to boost adherence.

Abstract A089: Role of Vardhamana Pippali Rasayana (VPR) in human breast cancer cells

Abstract Serious concerns include delayed diagnosis and adverse side-effects of conventional treatment leading to residual morbidity in Breast cancer (BC) globally. Traditional Indian medicines/herbs via combination of conventional cancer are gaining increasing acceptance worldwide, playing a pivotal role as proven by their efficacy evaluation studies. Many plants are known to reduce the cell proliferation and tumor development after their treatment. Vardhamana Pippali Rasayana (VPR), an Ayurvedic herbal preparation of pippali (Piper longum) in gradually increasing and tapering dose is used to treat many cancers without any adverse side-effects. However, its anti-cancer role in breast cancer is not known yet. The present study has explored the cytotoxic and apoptotic effects of VPR in triplicates on human breast cancer (MCF7) and normal breast epithelial (MCF10A) cell lines at different concentrations after extracting piperine in aqueous and hydro-alcoholic soxhlet extract (0.25 to 50 μg/μl). The cytotoxic activity was carried out by MTT assay and results showed that a low IC50 was observed at 3.75 μg/μl of VPR against MCF-7 as compared with normal breast epithelial cells. Detection of apoptotic cells using suitable Annexin V was done and there was a time-dependent increase in percentage of annexin V positive cells upon treatment. The above results indicate that VPR may have a strong anti-cancerous potential. But other functional assays are warranted to validate the efficacy of the drug against breast cancer which are under progress in our laboratory. Citation Format: Dr.Richa Tripathi, Shivam Singh, Subhash Gupta, VG Huddar, Tanuja M Nesari, Ashok Sharma. Role of Vardhamana Pippali Rasayana (VPR) in human breast cancer cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A089.

Breast cancer screening awareness, practice, and perceived barriers: A community-based cross-sectional study among women in south-eastern Bangladesh.

Breast cancer is a leading cause of mortality in Bangladesh. An early-stage screening is the best way to reduce both the morbidity and mortality burden of breast cancer. The study evaluated awareness, practice, and perceived barriers towardbreast cancer screening in Bangladesh. A community-based cross-sectional study was conducted from October 2021 to December 2022 in Chattogram, Bangladesh, where 869 women (18 years or above) were randomly selected in this study. Among 869 participants, 47.3% of women were recruited from urban areasand 52.7% participated from rural areas. Only 32.68% of respondents (urban vs. rural: 44.28% vs. 22.27%) were aware of breast self-examination (BSE) and 52.47% of respondents (urban vs. rural: 63.75% vs. 42.36%) had ever heard Clinical Breast Examination (CBE), respectively. Among the respondents, 27.73% (urban vs. rural: 40.15% vs. 16.59%) performed their BSE, and only 14.61% of respondents (urban vs. rural: 21.90% vs. 8.08%) had ever visited for CBE. Women residing in rural areas were approximately three times (AOR: 0.36[95%CI: 0.25-0.52], AOR: 0.37[95%CI: 0.23-0.58]) less likely to perform BSE and CBE, respectively, than urban dwellers. We found that higher-educated women tend to do more BSE and CBE than women with low levels of education. Perceptions of having "no symptoms" and being "risk-free" are leading barriers to breast screening among women. Poor awareness and practice were observed in screening among the urban and rural women in Bangladesh. Urban area dwellers had comparatively better understanding and practice than rural dwellers. We think extending health education and health promotion activities towardbreast cancer screening is essential in this region.

Exploring&amp;nbsp; the Awareness of Mammographic Screening for Breast Cancer and Identifying Barriers to Refrain from Screening:&amp;nbsp; Mini Review of the Literature

One of the most important factors to be addressed regarding breast cancer (BC) mortality and morbidity is the identification of BC at a late stage due to a lack of awareness of early detection methods of BC. Mammography can be emphasized as a foremost vital facet in the early detection of breast cancer as a screening tool. A mini review of the literature was performed to explore the concepts of awareness of screening mammography for breast cancer under three main aspects. There, the knowledge, attitude, and practice of women in mammographic screening were focused meanwhile identifying the common barriers for women to refrain from undergoing mammographic screening for breast cancer. The studies included various categories of participants especially subcategorized under their personal history or demographic characteristics. Therefore, the correlation of these factors with their awareness level has also been focused. Further, the barriers to screening mammography encountered by women were included. Therefore, this mini-review highlights the different levels of awareness of mammographic screening among females and the common reasons for avoiding screening. It concludes the benefit of bringing the knowledge of females to a considerably positive juncture by utilizing escalating awareness programs, hence minimizing the common causes of refraining from screening mammography.

The relationship between age and mortality and morbidity of patients diagnosed with breast cancer: a retrospective clinical study

Objective: Breast cancer, the most common malignancy among women, is a universally challenging health problem. It is a known fact that the incidence of breast cancer increases with age. In addition, mortality and morbidity increase with age. For now, it does not seem possible to reduce the incidence of breast cancer but it is possible to limit deaths caused by it. Patients are encouraged to get early diagnosis and age-appropriate screening tests. Because regular screening and early diagnosis are very important in improving breast cancer outcomes. Factors such as age, hormonal status and genetics are associated with the incidence of breast cancer. In this study, we aimed to contribute to the literature by examining age-related mortality and morbidity of breast cancer.&#x0D; &#x0D; Method: This study was carried out at a University Hospital. The sample consisted of 214 women between 01.09.2018/01.09.2022 diagnosed with breast cancer, aged 30 to 80 years.&#x0D; &#x0D; Results: The mean age of women was 51.9 ± 7.6 years, with 52.8% being

Abstract B072: Reproducibility of plasma metabolome over 1 year in a population-based study of Black breast cancer survivors

Abstract Background: African American/Black women have higher rates of breast cancer (BrCa) mortality and morbidity than White women. The metabolomics approach using blood samples from epidemiological studies has the potential to elucidate pathways or uncover biomarkers for adverse BrCa outcomes. Therefore, understanding the within-person reproducibility of the blood metabolome of BrCa survivors and factors that influence metabolite levels over time is crucial. However, the stability of blood metabolome among Black BrCa survivors is unknown. Objective: This study aimed to estimate the within-person reproducibility of metabolites over 1 year via global untargeted metabolomic profiling of plasma samples collected in the Women’s Circle of Health Follow-Up Study (WCHFS), a population-based longitudinal study of Black BrCa survivors in New Jersey. The study also aims to identify factors associated with reproducibility. Methods: We estimated the metabolite reproducibility among 61 Black women with BrCa diagnosed between 2012 and 2017 in WCHFS. Plasma samples were collected once for each participant at ~2 and 3 years post-diagnosis, respectively, and analyzed at Metabolon via ultrahigh performance liquid chromatography-tandem mass spectrometry. Using a mixed-effects model, we calculated the intraclass correlation coefficients (ICC) for each metabolite by dividing the between-person variance by the total variance (i.e., within- and between-person variances). ICCs were compared by age, obesity status, estrogen receptor (ER) status, and seasons, fasting status and time interval between two visits when blood samples were collected. Statistical significance was determined using the Wilcoxon test. Results: Of the 857 named metabolites identified after excluding those undetectable in ≥80% of samples or with a coefficient of variance≥0.25, the median ICC was 0.58 (interquartile range [IQR]: 0.44-0.70). 16.6% had high within-person reproducibility (ICC≥0.75), spanning across all metabolite classes, while 65.6% had an ICC within 0.4-0.75, and the remaining 17.9% had an ICC&amp;lt;0.4. Significant differences in ICCs were noted by participants’ age (median ICC [IQR; same below]: 0.56 [0.40 - 0.68] for younger women, i.e. ≤ 55.6 years vs. 0.61 [0.44 - 0.73] for older women), obesity status (0.55 [0.40 - 0.68] for non-obese vs. 0.62 [0.46 - 0.75] for obese), and ER status (0.56 [0.41 - 0.68] for ER+ vs. 0.62 [0.45 - 0.79] for ER-). The reproducibility also differed by fasting status (0.63 [0.45 - 0.77] for fasting vs. 0.53 [0.39 - 0.67] for non-fasting), but not the seasons or time interval between blood collections. Conclusion: The within-person reproducibility of plasma metabolites over 1 year among Black breast cancer survivors was generally reasonable, suggesting a single-time-point measurement could be useful in evaluating associations between metabolites and BrCa outcomes. However, the reproducibility varied across metabolites and was influenced by participant characteristics and certain sample collection conditions, which need consideration in future analysis or design. Citation Format: Bo Qin, Madhir Vyas, Steven C. Moore, Xiaoyang Su, Eileen White, Christine B. Ambrosone, Kitaw Demissie, Chi-Chen Hong, Elisa V. Bandera. Reproducibility of plasma metabolome over 1 year in a population-based study of Black breast cancer survivors [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B072.

Breast Cancer Awareness Among Women in Saudi Arabia: A Systematic Review.

Breast cancer (BC) is the most prevalent cancer worldwide, and second most common cause of cancer-related deaths among women worldwide. Early detection of BC significantly improves prognosis; thus, awareness is an important aspect of BC morbidity and survival as well as the economic burden. This systematic review aimed to explore awareness of BC among women in Saudi Arabia. A systematic search was performed using Medline, Scopus, the Directory of Open Access Journals (DOAJ), and Google Scholar for all cross-sectional studies conducted in Saudi Arabia, published after the year 2000 and in English. The quality assessment of the included studies was performed using the AXIS tool. The total number of included articles after full-text assessment was 13 articles that were conducted between 2005 and 2022. The sample size of all the articles was 7,562 women. All the studies categorized BC awareness into low, moderate, and high groups. The level of low awareness among women reached 66.3% (n=2808), 13.5% (n=570) had moderate awareness levels, and 20.2% (n=858) had high awareness levels. Furthermore, 59.4% (n=1446) of the participants did not perform breast self-examination (BSE) regularly. The level of awareness and knowledge regarding BC and BSE was significantly low among women in Saudi Arabia, as all included studies except one have indicated. We highly recommend and urge the implementation of effective special programs and campaigns to raise awareness regarding BC and integrating BSE into school health programs dedicated to women living in Saudi Arabia.

Ethnicity-specific BRCA1, BRCA2, PALB2, and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus.

Mountain areas of the North Caucasus host several large ethnic communities that have preserved their national identity over the centuries. This study involved high-grade serous ovarian cancer (HGSOC) and breast cancer (BC) patients from Dagestan (HGSOC: 37; BC: 198), Kabardino-Balkaria (HGSOC: 68; BC: 155), North Ossetia (HGSOC: 51; BC: 104), Chechnya (HGSOC: 68; BC: 79), Ingushetia (HGSOC: 19; BC: 103), Karachay-Cherkessia (HGSOC: 13; BC: 47), and several Armenian settlements (HGSOC: 16; BC: 101). The group of BC patients was enriched by young-onset and/or family history-positive and/or bilateral and/or receptor triple-negative cases. The entire coding region of BRCA1, BRCA2, PALB2, and ATM genes was analyzed by next-generation sequencing. A significant contribution of BRCA1/2 pathogenic variants (PVs) to HGSOC and BC development was observed across all North Caucasus regions (HGSOC: 19-39%; BC: 6-13%). Founder alleles were identified in all ethnic groups studied, e.g., BRCA1 c.3629_3630delAG in Chechens, BRCA2 c.6341delC in North Ossetians, BRCA2 c.5351dupA in Ingush, and BRCA1 c.2907_2910delTAAA in Karachays. Some BRCA1/2 alleles, particularly BRCA2 c.9895C > T, were shared by several nationalities. ATM PVs were detected in 14 patients, with c.1673delG and c.8876_8879delACTG alleles occurring twice each. PALB2 heterozygosity was observed in 5 subjects, with one variant seen in 2 unrelated women. This study adds to the evidence for the global-wide contribution of BRCA1/2 genes to HGSOC and BC morbidity, although the spectrum of their PVs is a subject of ethnicity-specific variations. The data on founder BRCA1/2 alleles may be considered when adjusting the BRCA1/2 testing procedure to the ethnic origin of patients.