Breast Cancer In Women Research Articles

Pattern of Breast Cancer in Women at Child-bearing Age, its Risk Factors and Clinicopathological Evaluation in Tertiary Level Hospital

Background: Carcinoma breast is the leading cancer in female in Bangladesh, increasing significantly due to urbanization and adoption of western life style. Objective: This study aimed to systematically understand the pattern of breast cancer, its risk factors and clinicopathological evaluation in women at their childbearing age. Methods: A cross sectional observational study, data was collected from 50 patients of histopathologically confirmed breast cancer in the department of Surgery, Combined Military Hospital, Dhaka from 2022 to 2023. Results: The majority of the cases were 41-45(42%) years age with mean presentation was 43.55 (SD-/+9.63) years. Invasive ductal carcinoma was the most common subtype 86%, followed by ductal carcinoma in situ (8%). Of the cases 2% were nullipara and 46% had two children. Median age of at 1st birth was 21 years. A significant proportion (16%) had family history of breast cancer. 98% patients gave history of breast feeding. Conclusions: Breast cancer is increasingly occurring in younger age groups in Bangladesh, results suggested a mixture of different factors in women like age of menarche, age of first child birth, parity, history of breast feeding and family history poses higher risk for breast cancer. J Rang Med Col. March 2024; Vol. 9, No. 1:16-21

Investigation of the Relationship Between Breast Cancer Awareness and Health Literacy in Female Textile Workers

Introduction: The level of breast cancer awareness among women may vary depending on their level of health literacy. Aim: This study aims to investigate the relationship between breast cancer awareness and health literacy among female textile workers. Methods: This is a descriptive and correlational study. The study population consisted of women employed as workers in a textile company. The sample included 360 female workers as participants. The 'Information Form', the 'Breast Cancer Awareness Scale', and the 'Health Literacy Scale' are the data collection instruments used in the study. The study data were analyzed using SPSS 22.00 and G*Power 3.1 software packages. Percentage, frequency, independent samples t-test, ANOVA, and regression analyses were used to evaluate the data. Results: The results showed that 73.6% of the participants did not perform regular breast self-examination, and 79.7% had never undergone mammography. Significant positive correlations were observed between women's breast cancer awareness and the functional, interactive, and critical sub-scales of health literacy (p

Abstract PO3-02-09: Breast cancer in women under the age of 40 years.A south Wales UK reflection on incidence, tumour biology and outcomes over 10 years

Abstract Introduction: The incidence of breast cancer in the under 40-year-old age group is approximately 7% (Anders et al., 2009). Studies suggests that the management of Breast cancer in adolescent and young women is more challenging, with this age group under-represented in clinical trials. We investigated the management and outcomes of a cohort of 98 patients seen between 2013 and 2023 in the Hywel Dda NHS University Health Board, Wales, UK. Methods: A retrospective review was performed. Demographic, surgical and outcome data for patients under the age of 40 years was collated and analysed. Results: The cohort size was 98, representing 2.45% of the breast cancer population treated in the Health Board during this timeframe. The age of the cohort ranged from 23 years to 40 years, 12 out of 98 (12.24%) were under 30 years. Mean age was 35.28 years. Unfortunately, 8.16% (8/98) of the cohort died between 12 months to 96 months. Two patients were lost to follow up. Tumour biology results confirmed that most of the cohort had invasive ductal carcinoma (IDC), with 13.27% Grade 1, 37.76 % Grade 2 and 40.82% Grade 3. There were 4 (4.08%) invasive lobular carcinomas (ILC) in the cohort, 2 Grade 2 and 2 Grade 3. The remaining tumour groups were, 1 case of DCIS (Grade-2 intermediate grade), Grade-1 mucinous carcinoma, 1 Grade-1 ductal-lobular breast cancer and 1 medullary carcinoma. 10.20% of the cohort had triple negative cancers (ER, PR, Her-2 negative) and 10.20% were ER, PR, HER2 positive [Triple positive]. 40.82% metastatic axillary lymph nodes involvement on histology either on presentation or following sentinel node biopsy. Operative details confirmed that the 51.02% (50/98) of the cohort underwent mastectomy. 10 out of those 50 patients underwent contralateral risk reducing mastectomy .46 patients had breast conservation surgery. One patient is awaiting surgery, the other has been diagnosed with metastatic breast cancer at diagnosis. Patients received both neoadjuvant and adjuvant chemotherapy depending on initial assessment and MDT discussion [ACP, FEC, Taxane and platinum-based chemotherapy, Anti Her-2]. NAC was provided for all HER-2+ patients. Endocrine treatment and ovarian function suppression, and adjuvant Radiotherapy was also given. Some patients had a complete pathological response to NAC; however, some did not respond well. In addition, 10.20% of the cohort underwent bilateral salpingo-oophorectomy during their treatment and follow up. Genetic assessment confirmed that 3/98 (3.06%) of the cohort were BRCA2 positive, one BRCA1 carrier, 2 patients were BRCA negative, two have been referred for genetics assessment and two still awaiting consultation with genetics. In one patient somatic mutation was found in PTEN, BIRC3, HRAS, TP53, PMS, (5 gene panel). In one patient, panel was reassuring. PALB-2, TP53 was also reassuring in one patient. One patient who passed away at the age of 34 did not have any alteration in 5 gene panel. Three patients developed other malignancies during the 10-year period: 1 uterine, 1 cervix, 1 papillary thyroid cancer. 6/98 (6.12%) developed metastatic disease and one developed a local recurrence. One patient developed metastasis while pregnant, and by contrast one patient gave birth to a baby after stopping her endocrine treatment. One patient who passed away had no response to neoadjuvant chemotherapy (NAC). Discussion: The results from the cohort confirm that the incidence of TNBC and triple positive cancers is like that found in the general breast cancer population (10-15%). Our engagement with the genetics team has increased since the initial 2013 cohort. There is now an established system for referrals for young women with breast cancer. It is probably not surprising that other primary invasive cancers were found, whilst on follow up. Citation Format: Sohail Khan, Saira Khawaja, Yousef Sharaiha, Asma Munir, Anita Huws. Breast cancer in women under the age of 40 years.A south Wales UK reflection on incidence, tumour biology and outcomes over 10 years [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 PO3-02-09.

Abstract PO5-03-08: Detection and quantification of triple-negative breast cancer (TNBC) across ethnicities through analysis of cell-free DNA (cfDNA) methylation

Abstract Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype contributing to race-related outcome disparities in breast cancer. These disparities are partly explained by the higher burden of TNBC in Black women, less access to new mammography technologies, and further compounded by limited efficacy of screening mammography in early detection of TNBC (Newman L & Mitchell E, J Natl Med Assoc 2023). To better understand these disparities, we compared results from the Galleri® multi-cancer early detection (MCED) test and the tumor methylated fraction (TMeF) tumor quantification algorithm in a population of TNBC patients across different stages and self-reported ethnicities (SRE). Methods: Within the case-control Circulating Cell-free Genome Atlas third substudy, we performed MCED testing and TMeF estimation in 507 women with breast cancer, 84 of whom had TNBC. The MCED test detects methylation patterns associated with circulating tumor DNA (ctDNA) to identify a common cancer signal and predict a cancer signal of origin. Tumor methylated fraction (TMeF) is an estimate of ctDNA abundance using machine learning models trained on whole-genome bisulfite sequencing of tumor biopsy tissue. We used SRE to compare results between non-Hispanic Black and White participants and those of other (Hispanic, Asian, Pacific Islander) or unreported ethnicities for both cancer detection by MCED test and ctDNA abundance estimation by TMeF. Results: In Black women, 19 (49%) of 39 diagnosed breast cancers were TNBC, compared to 58 (15%) of 396 breast cancers in White women and 7 (13%) of 52 breast cancers in women of other or unreported ethnicities. The MCED test did not detect Stage I TNBC (Table 1). In patients with Stage II-IV TNBC, the MCED test successfully detected a cancer signal in 16 (94%) of 17 Black women, 31 (72%) of 43 White women, and 6 (100%) of 6 women of other or unreported ethnicities (Table 1). When we examined the TMeF in these patients using a two-way ANOVA, we found a significant difference in mean TMeF by cancer stage (p < 0.001) but no significant difference in mean TMeF between SRE groups (p = 0.09) with the distribution of TMeF (Table 2). The ANOVA additionally found a significant interaction between cancer stage and SRE (p < 0.001) that could represent an impact of stage on TMeF that varied by SRE or differences in cancer stage distribution by SRE. Conclusions: In this pilot study, we observed that MCED testing was effective in detecting Stage II, III, and IV TNBC across SRE. These findings, in combination with the association of estimated ctDNA abundance with cancer stage but not patient SRE, provide hypothesis-generating evidence that analysis of methylation signals from across the genome can provide meaningful TNBC screening/detection information, independent of self-reported race/ethnicity. Table 1. MCED cancer detection rate by stage and SRE among TNBC patients. Table 2. Tumor methylated fraction (TMeF) by stage and SRE among TNBC patients. Citation Format: William Cance, Edison Liu, Margaret Antonio, Timothy Shaver, Stephannie Shih, Bong Chul Chu, Kathryn Kurtzman, Lisa Newman. Detection and quantification of triple-negative breast cancer (TNBC) across ethnicities through analysis of cell-free DNA (cfDNA) methylation [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 PO5-03-08.

Abstract PO5-09-09: Incidence of Breast Cancer in Hispanic Women Across the US: A Focus on Texas

Abstract Introduction Breast cancer (BC) is one of the most common cancers affecting the female population in the United States, particularly among the Hispanic community. According to the CDC, the incidence rate of new breast cancer cases in Hispanic women is 95.6 per 100,000 annually, and the mortality rate is 13.7 per 100,000 women annually. Texas is home to one of the largest Hispanic communities in the US. By analyzing the prevalence, mortality, and access to healthcare services in Texas, we can shed light on the unique aspects of breast cancer within the Hispanic population. Overall, this study will provide valuable insights and identify potential avenues for reducing disparities and improving healthcare outcomes for Hispanic women affected by breast cancer. Materials and methods This study used comparative data from State Cancer Profiles on the CDC and NIH databases. The database was used to generate an overall comparison of breast cancer in Hispanic women across different US states. Comparison factors analyzed include incidence, mortality, insurance, and screening efforts. Significant differences were noted especially in Texas. Graphs and quantitative data for comparison factors were generated. This data is from 2015-2019 unless noted. Results The incidence of breast cancer in Hispanic women in Texas (TX) is 93.5 (Age-Adjusted Incidence Rate-cases per 100,000) with a CI of (92.2-94.8). The incidence of BC in Hispanic women in the US averages 99.0 with a CI of 98.7-99.9. From the incidence data, Hispanic women in Texas have a lower overall incidence of BC compared to the rest of the Hispanic females in the US. When analyzing the mortality rate, Hispanic women in TX have an Age-Adjusted Death Rate (deaths per 100,000) of 15.2 (CI of 14.7-15.8). In the US, Hispanic women have an Age-Adjusted Death Rate (deaths per 100,000) of 13.0 (CI of 13.4-13.9). To analyze preventative measures, a graph reporting mammogram use in 2020 by state was gathered. In TX 2020, the estimated age-adjusted prevalence of mammograms among Hispanic females from 50-74 years old was 75.0% (CI of 67.0%-81.7%). Nationally, the age-adjusted prevalence among Hispanic females 50-74 years who reported mammogram screening in 2 years was 79.7% (CI of 76.6 – 82.4). As for Texas insurance rates in 2020, Hispanic women under 65 years old, 27.4 % reported being uninsured. In comparison, other ethnicities such as African American (non-Hispanic) women, 16.5% reported to be uninsured, and white (non-Hispanic) women in Texas 11.8 % reported to be uninsured. Additionally, to further analyze if the lack of preventative measures was causing women to have a higher mortality rate, the instance of late-stage diagnosis of BC in Texan Hispanic women was analyzed. The age-adjusted incidence rate of late-stage breast cancer in Hispanic women was reported to be 33.4 (CI of 32.6-34.2) and the national incidence of late-stage BC in Hispanic women is 35.0 (CI of 35.1-35.8). Conclusion Even with Texas having one of the largest Hispanic communities, Hispanic women with breast cancer in Texas are faced with obstacles that lead to an increase in their mortality rate. As seen in the results, Hispanic women have less incidence of BC (including late stage) than their equivalent across the US but Hispanic women in TX have higher mortality rates in comparison. This is additionally accompanied by a decrease in insured women and a decrease in the utilization of cancer screenings. Lack of access to affordable healthcare and lack of regulatory cancer screenings cause Hispanic women to meet their premature death. Further analysis of the effects of affordable health care or further molecular investigation of this population is encouraged to research to fully conclude the reason behind this population's disparities. Citation Format: Catalina Esguerra, Kemely Santos Barbosa, Roy Khalife, Anthony Magliocco. Incidence of Breast Cancer in Hispanic Women Across the US: A Focus on Texas [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 PO5-09-09.

Abstract PO3-13-10: Proteogenomic characterization of primary invasive breast tumors from young women compared to matched tumors from older women

Abstract Introduction: Breast cancer (BC) in women < 40 years old accounts for ~5% of BC diagnosed in the U.S. However, young women have more aggressive tumors and worse outcomes, including higher rates of recurrence and lower disease-free and overall survival, compared to older women. To better understand mechanisms for these disparities, an integrated proteogenomic study of tumors from young (< 40) and older (≥ 60) women was performed through the Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) program. Methods: 34 pairs of retrospectively collected, untreated primary breast tumors from young and older women, matched by immunohistochemistry (IHC) subtype and race, were selected from the Clinical Breast Care Project. Median patient follow-up was 7 years. Tumor cells were enriched by laser microdissection and analyzed using RNA sequencing, whole genome sequencing, global proteomics, phosphoproteomics, and reverse phase protein array (RPPA). Molecular and clinical data from tumors from young and old patients in the TCGA-BC and METABRIC studies, matched by IHC subtype and race, were used to corroborate findings from our cohort. Results are presented comparing young women and their tumors to their older counterparts. Results: Young women have worse clinical outcome measured by progression-free interval. Despite matching for IHC subtypes, tumors from young women are enriched for intrinsic basal-like subtype, BRCA1/2 germline mutations, and had fewer invasive lobular BCs. Differentially enriched molecules and pathways: A number of significantly differentially expressed genes (DEGs) and proteins were detected, which were able to separate luminal subtypes of BC by patient age. IRS1 and IRS2 were enriched at both transcript and protein levels; IRS1 has been reported to promote tamoxifen resistance. We observed limited overlap of DEGs between the APOLLO, TCGA, and METABRIC datasets. In contrast, 14 of the 28 significantly upregulated Cancer Hallmark pathways were also enriched in TCGA-BC and METABRIC datasets; suggesting targeting pathways, vs genes, may be more effective for therapeutic intervention. Integrated pathway/network analysis: Integrated pathway analysis of RNA and protein levels identified 5 Hallmark pathways upregulated in younger women, including ER response and proliferative pathways, and 6 downregulated immune-response pathways; 10 of the 11 were supported by the public datasets. Immune scores were also lower. Kinase substrate enrichment analysis identified 4 kinases with increased activity in tumors from young women. ESR1/ER: We identified for the first time a significant reduction of ER protein expression while confirming previously reported lower ESR1 gene expression and copy number variations. Surprisingly, integrated pathway analysis identified elevation of early and late estrogen responses in young women. ER activation, indicated by phosphorylated ER (pS118) normalized to total ER protein, was elevated in LumA tumors from young women. Conclusions: This first-ever integrated proteogenomic study shows that BC in young women is enriched for more aggressive molecular subtypes and for genes that promote tamoxifen resistance, exhibits lower immune pathways and immune scores, and shows enhanced ER responses despite lower gene and protein expression of ER. These findings may contribute to the understanding of the molecular mechanisms underlying worse outcomes of BC in young women, and offer new insight to therapeutic strategies. Disclaimer: The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views, opinions or policies of USUHS, HJF, the DoD or the Departments of the Army, Navy or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. Citation Format: Praveen Kumar Raj Kumar, Jianfang Liu, Anthony Soltis, Nicholas Bateman, Qingrong Chen, Lori Sturtz, Brenda Deyarmin, Mariaelena Pierobon, Tamara Abulez, Anupama Praveen-Kumar, Xijun Zhang, Trinh Nguyen, Chunhua Yan, Ying Hu, Kate Guion, Jeffrey Hooke, Albert Kovatich, Leigh Fantacone-Campbell, Brad Mostoller, Leonid Kvecher, Stella Somiari, Patricia Steeg, Sheila Rajagopal, Kathleen Darcy, Jerry Lee, Clifton Dalgard, Thomas Conrads, Emanuel Petricoin, Daoud Meerzaman, Matthew Wilkerson, APOLLO Research Network, Xiaoying Lin, Craig Shriver, Stanley Lipkowitz, Hai Hu. Proteogenomic characterization of primary invasive breast tumors from young women compared to matched tumors from older women [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 PO3-13-10.

Abstract GS02-13: Pregnancy after breast cancer in young women with germline BRCA pathogenic variants: results from an international cohort study

Abstract Background: Oncofertility counseling in BRCA carriers has unique challenges due to a possible negative impact of germline pathogenic/likely pathogenic variants (PVs) on reproductive potential and the indication to undergo risk-reducing bilateral salpingo-oophorectomy. While previous studies demonstrated the safety of pregnancy in women with prior breast cancer (BC) history, limited evidence exists in BRCA carriers specifically. We report the results of the largest study to date investigating likelihood of pregnancy after BC, reproductive and disease outcomes specifically in BRCA carriers. Methods: This was an international, multicenter, hospital-based, retrospective cohort study including young BRCA carriers with history of BC (NCT03673306). Eligible patients were women harboring germline PVs in BRCA1 and/or BRCA2 and diagnosed with stage I-III invasive BC at the age of ≤ 40 years between January 2000 and December 2020. BRCA healthy carriers or patients with BRCA variants of unknown significance, non-invasive BC, lack of follow-up, prior ovarian cancer or other malignancies without history of BC were excluded. Primary endpoints were pregnancy rate and disease-free survival (DFS). Overall survival (OS), BC specific survival (BCSS), pregnancy, fetal and obstetric outcomes were secondary endpoints. To mitigate the impact of guaranteed time bias, two survival analyses were performed: 1) Extended Cox model with occurrence of pregnancy as a time-varying covariate; 2) Case-control analysis by matching 1:3 patients with and without a pregnancy for type of BRCA PV, hormone receptor status, nodal status and year at diagnosis; moreover, each control had to have a disease-free interval longer than the time occurring between BC diagnosis and conception of the matched case. Results: From 78 centers worldwide, 4,732 patients were included, of whom 659 had at least one pregnancy after BC (pregnancy cohort) and 4,073 did not (non-pregnancy cohort). Patients in the pregnancy cohort were significantly more likely to carry BRCA1 PVs, to be younger at BC diagnosis, to have node-negative and hormone receptor-negative (HR-) BC (all p< 0.01). Pregnancy rate at 10 years was 22% (95% CI 21%-24%) overall, 18% (95% CI 16%-21%) and 26% (95% CI 24%-26%) in patients with HR+ and HR- BC, respectively (p< 0.01). Median time from BC diagnosis to conception was 3.5 years (IQR 2.2-5.3 years), significantly longer in patients with HR+ than HR- BC (4.3 vs 3.2 years, p< 0.01). Among 659 patients with a pregnancy after BC, 45 (6.8%) and 63 (9.6%) experienced an induced abortion or a miscarriage, respectively. Of the 517 (78.5%) patients with completed pregnancy, 54 (10.4%) had twins and 406 (78.5%) delivered at term (delivery ≥37 weeks). Among the 571 babies born, 5 (0.9%) had congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in DFS was observed between the pregnancy and non-pregnancy cohorts (unadjusted HR 0.97, 95% CI 0.82-1.15, p=0.74; adjusted HR [aHR] 0.99, 95% CI 0.81-1.20, p=0.90). Patients in the pregnancy cohort showed significantly better BCSS (HR 0.53, 95% CI 0.38-0.74, p< 0.01; aHR 0.59, 95% CI 0.41-0.86, p< 0.01) and OS (HR 0.52, 95% CI 0.38-0.72, p< 0.01; aHR 0.58, 95% CI 0.40-0.85, p< 0.01). Similar results were obtained in the case-control analysis. Subgroup analyses of survival endpoints according to patient, tumor and treatment characteristics will be presented at the conference. Conclusions: In this global study, 1 out of 5 young BRCA carriers conceived within 10 years after a BC diagnosis, higher than rates previously reported in unselected young BC populations. Pregnancy following BC in BRCA carriers did not appear to adversely impact maternal prognosis or fetal outcomes. These findings should be incorporated into oncofertility counseling of young BRCA carriers with BC. Citation Format: Matteo Lambertini, Eva Blondeaux, Elisa Agostinetto, Anne-Sophie Hamy-Petit, Hee Jeong Kim, Camila Chiodi, Rinat Bernstein-Molho, Florentine Hilbers, Katarzyna Pogoda, Estela Carrasco Lopez, Kevin Punie, Jyoti Bajpai, Michail Ignatiadis, Halle Moore, Kelly-Anne Phillips, Angela Toss, Christine Rousset-Jablonski, Fedro Alessandro Peccatori, Tiphaine Renaud, Alberta Ferrari, Shani Paluch-Shimon, Robert Fruscio, Wanda Cui, Stephanie Wong, Claudio Vernieri, Kathryn Ruddy, Maria Vittoria Dieci, Alexios Matikas, Mariya Rozenblit, Cynthia Villareal Garza, Laura De Marchis, Lucia Del Mastro, Fabio Puglisi, Maria Del Pilar Estevez-Diz, Kenny A. Rodriguez-Wallberg, Bela Mrinakova, Sarah Meister, Luca Livraghi, Florian Clatot, Rinat Yerushalmi, Carmine De Angelis, Rodrigo Sánchez-Bayona, Icro Meattini, Natalia Cichowska-Cwalińska, Martine Berlière, Mahmoud Salama, Ugo De Giorgi, Amir Sonnenblick, Hatem Azim, Ann Partridge. Pregnancy after breast cancer in young women with germline BRCA pathogenic variants: results from an international cohort study [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 GS02-13.

Abstract PO1-08-11: The survival rate of hereditary breast cancer in young women of Kazakh population

Abstract Background The study focused on determining survival rates between breast cancer patients with various germinal mutations and those without mutations among Kazakh women. Methods The study included 222 female patients of Kazakh ethnic group diagnosed with stage I-IV stage breast cancer at the age up to 40 years old. DNA samples were tested by next-generation sequencing on the MiSeq Illumina platform using Trusight Cancer kit for the analysis of 94 genes and 287SNPs. Information about dates of diagnosis and death retried from cancer registry system. Survival analyses were performed and compared mutation carriers and non-carriers subgroups. The 5-year survival was calculated using the Kaplan-Meier method. Results Next generation sequencing test identified 11 various pathogenic mutations in 57(25.7%) of overall 222 patients. The 5-year survival analysis for mutation carriers were 72.1%and 82.1% for non-carriers, with no statistically significant difference(P0.232). When stratified by mutational type, the 5-year survival rates were 71.8% for BRCA1 carriers, 81.3% for BRCA2, 53.35% for TP53 and 50% for moderate risk gene PALB2 mutation. These findings suggest that mutations in certain genes may be associated with differences in survival outcomes. Conclusions In breast cancer patients of Kazakh population similar to the world prevalence and predictive value of germline mutations have been found. A subcohort of mutation carriers and non-carriers demonstrated no significant difference in 5-year survival rate which may be associated with an early onset of disease, high-risk predictor of poor prognosis. Long-term survival and detailed PFS will be published according to information of follow-up visits and the cancer register system. Citation Format: Dilyara Kaidarova, Nazgul Omarbayeva, Aliya Abdrakhmanova, Oxana Shatkovskaya, Dilyar Omarov. The survival rate of hereditary breast cancer in young women of Kazakh population [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 PO1-08-11.

Abstract PO3-09-05: Potential novel treatments for high-risk subsets of breast cancer in postpartum and African American women

Abstract Semaphorin 7a (SEMA7A) is a neuroimmune molecule first recognized for its roles in axonal guidance and inflammation. More recently, SEMA7A has emerged as a driver of tumor progression in multiple types of cancer including lung, glioblastoma and breast. Our studies have focused on the roles of SEMA7A in promoting tumor cell growth and survival as well as invasion and metastasis in mouse models including xenograft and syngeneic. Using patient samples and datamining we have shown that SEMA7A can predict for recurrence in women with postpartum breast cancer (PPBC), or breast cancers diagnosed within 10 years of recent childbirth, and SEMA7A mRNA expression in TCGA is highest in young and African American (AA) women with BC, who typically have poor prognosis. Additionally, our analysis of the Cancer Genome Atlas (TCGA) breast cancer (n=593) and METABRIC cohorts (n=2,136) revealed that SEMA7A is increased in invasive disease and in the top 9% and 27% of upregulated genes (p=1.09E-19&p=0.009), respectively. Additionally, ~1.2 (TCGA) and ~1.1 (METABRIC) fold increases in SEMA7A mRNA conferred significantly decreased 5-year survival rates (p=0.009&p=0.002) and SEMA7A was in the top 4% of mRNAs upregulated in patients who died within 5 years of diagnosis 20,24-26. Cumulatively, these results suggest that identifying therapeutic vulnerabilities of SEMA7A+BC, or direct targeting of SEMA7A, could improve prognosis for these high-risk populations. We have identified several targets in pre-clinical models of SEMA7A+BC that include clinically available, FDA approved drugs, as well as novel inhibitors that exhibit efficacy. In published studies, we have shown that venetoclax, a Bcl-2 inhibitor, reverses ER+SEMA7A+BC resistance to endocrine therapy in mouse models. In unpublished studies, we have extended our observations in ER+SEMA7A+BC to show that alpelisib and a novel PI3K kinase inhibitor, GCT-007, both inhibit growth of human and mouse mammary tumor cells. Furthermore, in models of ER-SEMA7A+BC where we have shown cells to be resistant to chemotherapy, we have utilized age matched cell lines from AA and CA women to dissect the downstream pro-survival signaling that is mediated by SEMA7A and we have shown that anti-PD-1 and anti-PD-L1 therapies are efficacious in reducing tumor growth in vivo. Finally, we have developed a novel monoclonal antibody-based therapy that directly targets SEMA7A signaling via pro-survival pathways and inhibits tumor growth in vivo and in vitro. Collectively our results suggest that SEMA7A+BC should be identified clinically, and alternative treatments advised for this high-risk subset of breast cancer. Citation Format: Traci Lyons, Lyndsey Crump, Rachel Steinmetz, Kelsey Kines, Heather Fairchild, Alan Elder. Potential novel treatments for high-risk subsets of breast cancer in postpartum and African American women [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 PO3-09-05.

Abstract PO1-14-09: Age-related remodeling of the systemic and breast microenvironment promotes a tumor-permissive locale for ER+ breast cancer in older women

Abstract Introduction: The peak incidence of ER+ breast cancer occurs in women around the age of 70. Compared to younger cohorts, we and others have shown that older patients with ER+ breast cancer have an enrichment of luminal disease and experience fewer recurrences, suggesting overtreatment. Differences in the biological phenotypes of tumors in older women remain poorly understood and treatment remains challenging as older patients are underrepresented in clinical trials. In this study, we hypothesized that aging alters both local and systemic hormones and inflammatory cytokines, creating a permissive environment for tumor formation and growth. To address this hypothesis, we employed a systems biology approach across multiple model systems and tissue samples. Methods: Our study included specimens from two cohorts of patients: (1) n = 90 women without breast cancer obtained from the Komen Tissue Bank, from whom we obtained matched plasma and non-cancerous breast tissue (n = 30 across age groups comprising of young donors (35-45yo), middle-aged donors (55-69yo), and older donors (≥ 70yo); and (2) n = 115 women with ER+ breast cancer (n = 25 young patients, n = 57 middle-aged patients, and n = 33 older patients) obtained from our institutional biobank, including matched plasma, tumor tissue, and tumor-adjacent tissue. From each of these sets of specimens, we measured estrogen disposition using mass spectrometry, a 22-plex panel of inflammatory markers, and transcriptomic changes using RNA-seq. Using scRNA-seq and multiplexed IHC, we further characterized the immune changes that occur with age. Lastly, we used an aged, carcinogen-induced ER+ tumor model in F344 rats (obtained from the NIA) to model tumor development and growth. Results: In the plasma, estradiol (E2) drastically decreased in post-menopausal women, leaving estrone (E1) as the predominant circulating estrogen in older women. However, the breast tumor microenvironment (TME) showed comparable levels of E1 and E2 across age groups. Multi-class concordance analysis of breast cancer tissue from RNA revealed significant increases in gene expression of the HSD17B7 enzyme and decreases in HSD17B2 enzyme across age, likely elevating local E1-to-E2 conversion and yielding high local E2 levels despite low circulating levels specifically in older women. In older patients with ER+ breast cancer, there was a significant increase in a chemokine network characterized by CCL2 and CXCL9 within the TME. scRNA-seq revealed enrichment of inflammatory M2-like macrophages in the aged TME. Immune dysfunction and decreased immunosurveillance in older patients manifested with widespread decreases in the presence of cytotoxic lymphocytes and decreased pathway enrichment of key immune pathways, such as JAK/STAT and IFNy signaling. mIHC analysis revealed decreases in CD4 and CD8 T cells and increases in M2-like macrophages in older patients in both tumor and stromal regions. Lastly, in the carcinogen-induced F344 rat model, aged rats (~ 24mo, human equivalent 60-70yo) had a shorter tumor-free interval than the younger rats (~ 4-6mo, human equivalent 20-30yo), likely due to increases in tumor-promoting inflammation and decreased immune surveillance. Ongoing mechanistic work is focused on macrophage-patient derived organoid co-cultures evaluating the functional relevance of E2, CCL2, and CXCL9 in shaping the aged TME. Conclusions: Our study of systemic and local breast hormones and cytokines in both healthy individuals and breast cancer patients showed that older women with ER+ breast cancer harbor different systemic and local environments compared to younger women. The aged TME is characterized by high E2, cytotoxic lymphocyte depletion, and immune dysfunction, creating a permissive environment for tumor formation. Future translational work should be aimed at chemo-preventative strategies to reduce the age-related chronic inflammation and immune dysfunction. Citation Format: Neil Carleton, Jian Zou, Sanghoon Lee, Dixcy Jaba Sheeba John Mary, Ruxuan Li, Jennifer Atkinson, Ziyu Huang, Hatice Osmanbeyoglu, Peter Lucas, Emilia Diego, Michael Lotze, George Tseng, Jagmohan Hooda, Ioannis Zervantonakis, Priscilla McAuliffe, Steffi Oesterreich, ADRIAN LEE. Age-related remodeling of the systemic and breast microenvironment promotes a tumor-permissive locale for ER+ breast cancer in older women [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 PO1-14-09.

Abstract PO1-02-14: Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort

Abstract Background Compared to middle-aged women, older women have a higher risk of breast cancer death. Whether the increased risk of breast cancer death is present in all subgroups of older adults with breast cancer, or negligible in the subgroups receiving adequate surgical and oncological treatment, has been debated. We studied long-term prognosis by age and subtype, adjusting for stage, treatment, socioeconomic status and comorbidity, clarifying which subgroups of older patients that are at increased risk of breast cancer death. Methods In a nation-wide cohort of 45,949 women aged ≥60 years at diagnosis of breast cancer 1997-2014, we estimated crude probabilities of breast cancer death and from other causes using competing risk methods. Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) with 95% confidence intervals (CI. Results In this large population-based cohort study of older women with breast cancer, we found an increasing risk of breast cancer death with increasing age at diagnosis, both at 5- and 10-year follow up. The strong association between age and breast cancer death was found for all breast cancer subtypes, being most prominent in Her2-positive breast cancer. The age effect was also significant in Luminal A breast cancer where treatment opportunities are not necessarily affected by age. High-risk tumors were equally common in all age groups above 60 years. In multivariable analysis, stage, subtype, grade and treatment were important explanatory variables to the age-related differences in survival, while comorbidity and socioeconomic status contributed minorly. After adjustments, older age remained an independent risk factor for both overall and breast cancer survival. Older women with triple-negative (60-79 years) or Her2-positive (60-84 years) tumors had a 5-year risk of breast cancer death exceeding the risk of death by other causes. Conclusions Older women had a significantly higher risk of breast cancer death irrespective of breast cancer subtype, also in Luminal A disease where treatment opportunities are not necessarily affected by age. Table 3. Crude probabilities of breast cancer specific death and death by other cause (competing cause of death) at 5, 10 and 15 years. Table 4. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) Table 5. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) by age at diagnosis and subtype. Citation Format: Amelia Chiorescu, Anna L V Johansson, Antonis Valachis, Alexios Matikas, Jan Frisell, Lars Holmberg, Irma Fredriksson. Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort [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 PO1-02-14.

Abstract PO3-09-09: Interventions to improve adherence to oral endocrine therapy for prevention or treatment of breast cancer in African American women of low socioeconomic status

Abstract Introduction: Adherence to oral endocrine therapy (OET) for the prevention and treatment of hormone receptor-positive breast cancer (BC) is important as they reduce the risk of new or recurrent BC. OET adherence is greatly compromised in women of lower socioeconomic status (SES). We have recently reported that patients belonging to the African American race, with longer time on OET, and using OET in the prevention setting are more likely to be non-adherent to OET. Therefore, our study aims to design unique patient-centered interventions and pilot test their feasibility, acceptability, and effectiveness in improving OET adherence in African American women of low SES. Patients and Methods: This prospective study includes adult, African American women on OET for either the prevention or treatment of BC at Harris Health System in Houston, Texas, serving the underserved patient population with low SES. The first intervention is a motivational interviewing (MI) based telephone intervention consisting of an initial phone call followed by five monthly follow-up calls with an MI-trained pharmacy student. The second intervention is a theatre-based educational video with a script developed by a local African American playwright, featuring African American women. Three African American BC survivors with experience in taking OET consulted with the study team to convey their BC journey and explain challenges with taking OET. They provided feedback on the script and production of the educational video. Informed consent was obtained verbally via phone in the MI intervention and electronically for the educational video intervention. Individuals in both intervention groups were compensated with Walmart eGift cards. Pre- and post-intervention adherence was measured using the proportion of days covered (PDC) over 6-12 months and compared using a paired t-test. Participants also complete a survey at the end of the interventions to determine their acceptability. The survey responses were summarized descriptively. Results: For the MI intervention initiated in 20 patients, the median age and BMI of study participants was 61 years (range: 49-71) and 30.8 (range: 22.3-57.8) respectively. All participants identified their ethnicity as non-Hispanic or Latino. The majority of participants had hypertension (n=13, 65%) and/or hyperlipidemia (n=11, 55%) with depression (n=3, 15%) and diabetes (n=8, 40%) being less common. The most common stage of BC cancer was stage I (n=9, 45%), followed by stage II (n=4, 20%), stage 0 (n=3, 15%) and then stage III (n=2, 10%) and IV (n=2, 10%). Letrozole was the most common OET (n=13, 65%), followed by tamoxifen (n=3, 15%), anastrozole (n=2, 10%) and exemestane (n=2, 10%). Most participants were not on a CDK 4/6 inhibitor (n=18, 90%). The median number of years on therapy was 2.8 (0.6-4.5). The median pre-intervention PDC for OET was 0.7 (range: 0.2-0.9). The MI intervention is expected to be complete by October 2023 for all patients. For the educational video intervention, 7 out of the anticipated 25 participants have been enrolled in the intervention. All patients were taking OET for BC treatment and not prevention. Letrozole (n=3, 43%) and anastrozole (n=3, 43%) were the most utilized OET, followed by exemestane (n=1, 14%). While 5 participants (71%) in this intervention reported not missing any OET doses in the past week, 2 patients (29%) reported missing all 7 doses within the past week. After watching the educational video, most participants (n=6, 86%) reported that they strongly agreed to take their OET regularly. The recruitment of study participants for this intervention is ongoing. Conclusion: In this study, we report that MI and educational video interventions are feasible. The interventions and analysis of their effectiveness and acceptability are ongoing. Citation Format: Camille Johnson, Ann Adigwe, Nicole Ekezie, Bilqees Fatima, Zahra Majd, Keith Houk, Tejal Patel, Rob Shimko, Onyebuchi Ononogbu, Susan Abughosh, Meghana Trivedi. Interventions to improve adherence to oral endocrine therapy for prevention or treatment of breast cancer in African American women of low socioeconomic status [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 PO3-09-09.

Abstract PO2-08-03: Developing a polygenic risk score for precision prevention of estrogen receptor-positive (ER+)/HER2- breast cancer in Brazilian women

Abstract Polygenic risk scores (PRS) quantify the genetic risk of diseases based on risk alleles in genomic loci identified in genome-wide association studies (GWAS). As individuals of European ancestry are overrepresented in GWAS, PRS performance may vary in individuals of different ancestries. Brazil is the largest and most populated country in Latin America, with around 43% of admixed individuals, and data on breast cancer PRS performance for this population is lacking. We aimed to evaluate the performance of a breast cancer PRS with 313 SNPs generated with Europeans in Brazilian population. In this case-control study, we expect to include 1000 women age >= 18 years old with current or previous diagnosis of ER+/HER2- breast cancer. Germline DNA samples are genotyped with Illumina Infinium Global Screening Array-24 v3.0 chip. Controls are healthy woman previously genotyped with Global Screening Array-24 v1.0 chip. We selected the 313 SNPs PRS for ER+/HER2- breast cancer from PGS Catalog for evaluation. Quality control, imputation, PRS calculation and statistical analysis were performed in PLINK v2.0, Michigan server, PGS Catalog and R, respectively. We present the preliminary results for 1347 women (504 cases and 843 controls) included until March of 2023. After quality control and imputation, we calculated PRS for 1212 subjects (475 cases and 737 controls). Out of 313 SNPs, 211 were validated in our samples. For ER+/HER2- breast cancer, the odds ratio per SD of the 211-variant PRS (PRS211) was 1.363 (95% confidence interval [CI]: 1.211 to 1.537). Compared with women with average risk (40th-60th PRS percentile), women in the top 10% of PRS211 had a 1.623-fold increased risk (95% CI: 1.047 to 2.522). The area under the receiver operating characteristic curve of 0.581. Our preliminary results indicate that a PRS derived from European-ancestry population correlates with ER+/HER2- breast cancer in admixed Brazilian population, although with attenuated performance. Further work is needed to better characterize PRS risk stratification in admixed populations. Citation Format: Marina Candido Visontai Cormedi, Álison Luís Eburnêo Pereira, Fernanda Borchers Coeli-Lacchini, Sabrina Baroni, Lívia Mara Torres Bueno, Evelyn Ayumi Onga, Victor Girelli Piloto De Oliveira, Fabiana De Oliveira Buono, Aline Fares, Tatiana Strava Correa, Iasmin Alves Chirichela, Fernanda Peria, Romulado Barroso-Sousa, Rodrigo Santa Cruz Guindalini, Taisa Manuela Bonfim Machado Lopes, Rosimeire Aparecida Roela, Maria Aparecida Azevedo Koike Folgueira, Daniel Guimarães Tiezzi, Leandro Machado Colli, Liane Rapatoni. Developing a polygenic risk score for precision prevention of estrogen receptor-positive (ER+)/HER2- breast cancer in Brazilian women [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 PO2-08-03.

Abstract PO5-07-01: A novel clinical risk score that can accurately predict the survival of young breast cancer patients: A UAE-based cohort study

Abstract Introduction: Breast cancer (BC) in women below the age of 40 accounts for approximately 7% of all BC cases. According to studies, BC in younger women is more likely to have negative tumor characteristics and outcomes compared to older women. The rate of early-onset breast cancer in the United Arab Emirates (UAE) is higher than in the Western population (24%, previously reported). Young breast cancer patients in the UAE have worse adverse features, including a higher grade, a larger tumor size, and lymph node involvement, as we reported previously. Therefore, combining several clinical indicators to predict recurrence risk in our unique, heterogeneous young breast cancer group is needed. Aim:The aim of this study is to develop a statistical machine learning model that can predict survival and the risk of recurrence in a young breast cancer population seen and treated in a large-volume tertiary cancer center in the United Arab Emirates (Tawam Hospital). Methods: Early-onset breast cancer patients from a retrospective observational cohort study were included in this study (N = 904). A broad range of clinical data was collected. A multivariate ridge Cox regression model was performed using age, histology, molecular type (ER,PR,HER-2 status), T-stage, N-Stage, M-stage, grade, and BMI, and the interaction term age*BMI at the time of diagnosis. The primary outcome was time-to-death. A novel breast cancer risk score (BCRS) was developed as the linear predictor of the fitted-ridge Cox regression model. Breast cancer patients were categorized into low, medium, and high risk using the 33th and 66th centiles of the novel BCRS. A univariate Cox regression model was performed with a categorized BCRS as a predictor of time-to-death. Hazard ratios (HR) with a 95% confidence interval (95% CI) were estimated. Kaplan-Meier (KM) curves were plotted and compared using the log-rank test. Time-dependent sensitivity and specificity were computed at five- and ten-year follow-ups, respectively. Statistical analyses were performed in R version 4.2.3. Results: The median age was 36 years (IQR: 32–38), and 64% were Arabic. Fifteen percent had an event with a median duration of follow-up of 15.4 years (95% CI: 13.6–17.1). The estimated HR of the categorized novel BCRS in a univariate Cox regression model was 1.968 (95% CI: 1.075- 3.601) and 8.040 (95% CI: 4.695–13.769) for the intermediate and high-risk groups as compared to the low-risk group, respectively. KM curves show a clear separation in terms of survival between the three risk groups, p< 0.0001 (Figure 1). A cutoff value of -1.733 gives a sensitivity of 93.8 and 90.6 with corresponding specificities of 31.42 and 31.31 at five- and ten-year follow-up, respectively. Conclusion: This is the first study in the region that uses clinical data that combines several clinical characteristics and aims to design a statistical machine learning model to predict the risk of death from breast cancer. Our novel model can be used in daily clinical practice to identify high risk breast cancer patients and aid clinical decision-making in patients with breast cancer. However, further validation studies are needed. Figure 1:KM curves of breast-cancer survival for patients with low-risk (BCRS in [-2.32, -1.63], black curve), intermediate-risk (BCRS in [-1.64, -1.25], red curve), and high-risk BCRS in [-1.26, 1.41], green curve). Citation Format: Aydah Al-Awadhi, Mohammed Hourani, Mawada Hussein, Fatima Alkindi, Lina Wahba, Abla AlAgha, Alaa Shoqeir, Mouza AlShebli, Atlal Abusanad, Amar Ahmad. A novel clinical risk score that can accurately predict the survival of young breast cancer patients: A UAE-based cohort study [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 PO5-07-01.

Abstract PO5-08-11: Genetic Landscape of Early Breast Cancer in an Ashkenazi Jewish Cohort

Abstract Background: The Ashkenazi Jewish (AJ) population exhibits a distinctive mutation profile in BRCA1 and BRCA2 (BRCA1/2), characterized by 3 common founder mutations: BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. These 3 mutations are associated with 10% of invasive breast cancer (BC) cases among AJ women. However, the frequency of non-founder pathogenic variants in BRCA1/2 and other BC-related genes in AJ women with BC remains unclear. Methods: This retrospective study included AJ patients diagnosed with stage I-II human epidermal receptor growth factor 2 negative BC between 2004-2022 at the Weill Cornell Breast Center. We collected clinicopathological characteristics and genetic information to determine the frequency of predisposing mutations in BC and non-BC related genes in AJ patients with early BC. We also analyzed the clinicopathological characteristics and outcomes of patients with and without germline mutations in these genes. Results: The study included 232 self-identified AJ patients, with 98% being females. The median age at BC diagnosis was 62 years (IQR: 50-70). Stage I and II cancers accounted for 68% and 32% of cases, respectively. Hormone receptor positivity (HR+) was observed in 71% of patients, while 29% had triple-negative tumors. Genetic testing was performed on 88% (n=203) of the patients, while 5% of patients declined to undergo genetic testing. Among the tested patients, 12% (n=25/203) had pathogenic variants in BRCA1 or BRCA2, with 44% and 16% of these corresponding to the BRCA1 and BRCA2 founder mutations, respectively. Testing beyond BRCA1/2 genes was conducted on 154 patients, and only 6% (n=9/154) were found to have pathogenic variants in CHEK2, while no mutations were detected in other prevalent BC-related genes, including PALB2 and ATM. Fourteen-percent of patients had pathogenic mutations in other genes including APC, CFTR, FH, DIS3L2, FANCC, MUTYH, NF1 and VHL. The frequency of pathogenic BRCA1/2 variants was inversely proportional to the age at BC diagnosis: 50% (n=8/16), 21% (n=8/39), 15% (n=6/40), and 3% (n=3/108) of patients diagnosed at age < 40, 40-49, 50-59, and >60 years, respectively, had a pathogenic variant in either BRCA1 or BRCA2. The frequency of founder mutations varied according to age at diagnosis: 63%, 75%, 17%, and 100% for patients aged < 40, 40-49, 50-59, and >60 years, respectively. Patients with BRCA1/2 mutations exhibited higher-risk clinicopathological features compared to those without mutations, including a higher proportion of high histological grade (88%), and triple-negative tumors (76%). Mastectomy was the primary surgical treatment for 56% and 23% of patients with and without BRCA1/2 mutations, respectively. No difference in disease-free survival was found between patients with and without BRCA1/2 mutations with a median follow up of 3 years (IQR: 1-4). Conclusions: In our cohort, 17% of AJ patients with early BC carried a pathogenic variant in a BC-related gene, with BRCA1/2 being the most commonly affected genes. The proportion of pathogenic variants in BRCA1/2 showed an inverse correlation with the age at BC diagnosis, reaching up to 50% in patients diagnosed under the age of 40. These findings contrast with the lower prevalence of pathogenic variants in BRCA1/2 (38%) reported in the existing literature for this age group. Additionally, 8% of patients had pathogenic variants in other tested cancer genes carrying a genetic predisposition to colorectal cancer (CRC). These findings contribute to our understanding of the genetic landscape of early BC in the AJ population and emphasize the importance of comprehensive genetic testing, particularly among young patients. These results also suggest the need for earlier and more frequent CRC screening in a population of BC patients that may not be adhering to recommended guidelines. Furthermore, our study provides insight into how this genetic landscape may vary when analyzing late-stage BC in women of AJ heritage. Citation Format: Laura Munoz Arcos, Eleonora Nicolò, Maira Pires, Letizia Pontolillo, Leticia Varella, Tessa Cigler, Eleni Andreopolu, Anne Moore, Ashley Schreier, Carlos Munoz-Zuluaga, Lisa Newman, Georgia Syrnioti, Massimo Cristofanilli. Genetic Landscape of Early Breast Cancer in an Ashkenazi Jewish Cohort [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 PO5-08-11.

Abstract PO3-02-06: Predictive Factors for adjuvant radiation use in patients >70 years with pT1N0 HR+ breast cancers

Abstract Introduction: In 2004 the CALGB 9343 study reported that women >70 years of age with pT1NO hormone receptor positive breast cancer received no meaningful benefit from breast irradiation following lumpectomy. Although there was a modest reduction in local recurrence, there was no improvement in rates of mastectomy for local recurrence, distant metastases, 5-year overall survival (OS) and breast cancer specific survival therefore concluding that it was reasonable to omit radiation therapy in this group. An update of the CALGB 9343 study in 2013 with 10-year follow-up came to the same conclusion. Previous analysis of the National Cancer Database (NCDB) and the SEER database showed, however, that the majority of women with these characteristics were still receiving radiation therapy. We conducted this retrospective analysis from NCDB to identify factors associated with the use of radiation in this population. Methods: We reviewed the NCDB database and collected records of all breast cancer patients aged >70 years, who had hormone positive (HR+), pT1N0 disease between the years of 2004-2019. They were separated into radiation and non-radiation cohorts and then stratified based on ethnicity, age groups, insurance status, income quartiles, education quartiles, areas of residence, tumor size, comorbidities, diagnosis to treatment time, treatment facility type and geographic location. We then compared mortality between the two cohorts and completed a multivariate analysis to determine the demographic and clinical factors associated with the likelihood of receiving radiation. SAS was used for analysis and p-value < 0.05 was deemed as statistically significant. Results: 147,611 patients met the criteria of age > 70, pT1N0, HR+ treated with surgical lumpectomy. The majority of them were white, aged 70-75y, had Medicare, were in higher education and income quartiles and lived in metro areas (Table 1). 57.9% of the total study population received radiation. The possibility of receiving radiation decreased as age increased beyond 75 years. Uninsured patients, Medicare patients, those with comorbities, higher educational status as well as those who lived 20+ miles away from their treatment facility and treated at urban centers in central or south Atlantic areas were less likely to receive radiation. Those treated at Comprehensive community cancer programs and middle Atlantic areas were more likely to receive radiation. The possibility of radiation also progressively increased with tumor size. However, there were no differences observed when stratified by race, income status or chemotherapy use (Table 2). We also noted a small overall survival advantage for the radiation cohort (HR 0.77, p-value < 0.0001) which could be explained by the fact that patients without comorbidities were more likely to receive radiation. Discussion: Our results provide a real-world estimate of radiation use in pT1N0 HR+ early-stage breast cancer in women > 70 years. The major predictors of radiation use included younger age, low co-morbidities, insurance and institutions providing care. Lack of awareness about recent updates or concern about local recurrence could be contributing to the continued use of radiation. Although there are minor differences when stratified by demographics, it is concerning that the overall trend of radiation use has not significantly decreased over time. Since there is currently no data to support the routine use of radiation in this patient group as evidenced by randomized controlled trials, it is prudent to avoid radiation. This approach would help reduce healthcare costs, patient inconvenience and associated morbidity. Table 1 Baseline characteristics Table 2 Factors affecting radiation use Citation Format: Suma Sri Chennapragada, Runhua Shi, Shivani Sharma, Gary Burton. Predictive Factors for adjuvant radiation use in patients >70 years with pT1N0 HR+ breast cancers [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 PO3-02-06.

Abstract PO1-10-02: Breast cancer among transgender and non-binary patients on gender affirming hormone therapy: a single institution experience

Abstract Background: Estrogen exposure is a known risk factor for the development of breast cancer in women. Less clear is the risk posed by gender affirming hormone therapy (GAHT) in both transgender men and transgender women. We aimed to characterize the breast cancers that have arisen in our institution’s transgender patient population including biomarker profile, method of diagnosis, and stage at diagnosis. Methods: For this retrospective cohort study, patients from the Mount Sinai Health System were identified using the electronic medical record from 2016-2023. A cohort of transgender or non-binary patients with breast cancer was established by using ICD-10 codes for carcinoma in situ of breast (D-05) and malignant neoplasm of breast (C-50) and a diagnosis or medical history encompassing gender identity disorders (ICD-10-CM: F64) or a chief complaint related to transgender health. Chart review enabled selection of patients who have a history of GAHT. Patients with incomplete medical records were excluded from analysis. Results: 14 patients met criteria and were included for final analysis. Mean age at diagnosis was 51.7 (31-65) years and 86% (12/14) were at or above 40 years of age at diagnosis and eligible for routine screening mammography. The cohort encompassed six trans men (assigned female at birth), seven trans women (assigned male at birth), and one genderqueer person (assigned female at birth). Family history was not significant for most of the cohort. Two patients had a first-degree relative with a history of breast cancer; both were BRCA negative. Four patients (29%) were diagnosed via screening mammography; six patients (43%) were diagnosed after palpating a breast or axillary mass; and four patients (29%) had not undergone screening but were diagnosed via breast imaging mandated prior to planned chest masculinization surgery. At time of initial presentation, the diagnostic stage was DCIS in five patients (36%); LCIS in one patient (7%); stage 1 cancer in four patients (29%); stage 2 cancer in three patients (21%); and breast implant-associated anaplastic large cell lymphoma in one patient (7%). 50% (7/14) of patients had an active or past prescription for testosterone-based GAHT, and 50% (7/14) patients had an active or past prescription for estrogen-based GAHT. Mean duration of all GAHT prior to diagnosis was 16.6 years (mean duration of estrogen-based GAHT was 27.6 years and mean duration for testosterone-based GAHT was 5.7 years). Biomarker profiles were available for twelve patients; 8/12 (67%) patients were diagnosed with estrogen receptor (ER) positive cancer, four (33%) with ER negative cancers. Of patients on estrogen-based GAHT, three presented with ER+ and four presented with ER- cancers. 10/14 patients had bilateral mastectomies and 4/14 had lumpectomies. Discussion/Conclusion: The mode of cancer detection suggests that screening mammography is under-utilized among transgender and non-binary patients who use GAHT. This represents a health care disparity involving a vulnerable patient population. The biomarker profile among this population demonstrates that both estrogen-responsive and estrogen-nonresponsive cancers can arise in the setting of prior or ongoing gender affirming estrogen or testosterone. Citation Format: Nithya Krishnamurthy, Ethan Ravetch, Christina Weltz. Breast cancer among transgender and non-binary patients on gender affirming hormone therapy: a single institution experience [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 PO1-10-02.

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 PO5-25-09: rs2242652 POLYMORPHISM OF THE hTERT GENE IN WOMEN WITH BREAST CANCER

Abstract Introduction: Breast cancer is the most common neoplasm in women around the world. There are several risk factors for this cancer: sex, age, body mass index (BMI), hormone therapy, family history, genetic mutations, among several others. The vast majority of breast tumors are characterized as carcinomas and may originate from ducts or lobules. Immunohistochemistry is related to the expressions of the estrogen receptor (ER) and progesterone receptor (PR), as well as the expression of the human epidermal growth factor receptor 2 (HER2), cell proliferation or the absence of any expression from receptors on the tumor membrane. The telomeres protect the chromosomes natural endings from suffering DNA loss. Telomerase is a ribonuclear protein complex (RNA and protein) that neutralizes telomeres' shortening. Recurrent point mutations in the TERT telomerase promoter have been identified in several cancers, and the rs2242652 polymorphism is a single nucleotide change, and has been described as associated with breast cancer risk. Objective: The objective of this study is to analyze the TERT rs2242652 polymorphism in breast cancer women and to test the correlation of such data with the prognosis and various clinical variables. Methods: The study was conducted as an observational clinical study of women with breast cancer. A blood sample was collected from the patient and PCR was performed to extract the DNA and to analyze the telomerase polymorphisms in this population. To ensure a more descriptive analysis, the data was used in the construction of tables and graphs, that were then studied in a qualitative manner. The associations were analyzed through direct correlation tests and were followed by comparisons of categorization groups. Results and discussion: Fifty-four women presented polymorphism of the telomerase hTERT gene rs2242652. They were divided into two groups according to the A or G allele that confer the GA/AA and GG gene variants. It was found that the GA/AA group had a trend towards more aggressive tumors, presenting 33% triple negative and 22% of tumors with HER2 overexpression, different from the GG group: 19% triple negative and 10% HER2 overexpression. More aggressive T4 tumors, were more expressive in the GA/AA gene variant group representing 20% of the patients, whereas in the GG group they represented only 8%. Conclusion: The data found in this study on the telomerase TERT gene polymorphism rs2242652 with breast cancer refers to a tendency found in tumors that have a more severe prognosis, to associate with the gene variant linked to the A allele of this gene, however a larger sample number is required for statistical confirmation. Citation Format: Miriam Alvares, Elisa Mascarenhas, Joao Matos. rs2242652 POLYMORPHISM OF THE hTERT GENE IN WOMEN 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 PO5-25-09.

Abstract PO4-16-04: Decoding the immune landscape of breast cancer (BC) during pregnancy (PrBC): Impact of hormone receptors (HR) and tumor-infiltrating lymphocytes (TILs) phenotype on gene expression signatures

Abstract Introduction: PrBC is an uncommon malignancy with aggressive behavior. Its pathogenesis involves distinct immune mechanisms associated with maternal-fetal tolerance and tumor-host immunoediting. PrBC displays specific patterns of TILs with increased CD8+ cells. Gaining a comprehensive understanding of the molecular processes underlying this immune synergy is crucial for enhancing PrBC patients’ clinical management. Here, we sought to identify dysregulated immune-related genes in PrBC and explore their association with HR status and TILs. Methods: A total of n=75 PrBC (age range 26-43 years) and n=67 age-matched early-onset breast cancer (EOBC) in non-pregnant women (controls; age range 28-43 years) were selected from our Institutional registry. For all cases TILs were quantified according to the International TILs Working Group recommendations and profiled by IHC for CD4 and CD8. RNA was extracted from representative FFPE tissue blocks to perform the expression analysis of 395 genes involved in tumor-immune interactions using a targeted NGS panel (Oncomine™ Immune Response Research Assay, Thermofisher). Samples with >1,000,000 mapped reads and >800,000 valid reads were considered adequate. R package DESeq2 software 1.38.3 was used for sequencing depth differences normalization and differential gene expression analysis. Differentially expressed genes (DEGs) were identified based on a significant p-value (p< 0.05). Results: The comparison between PrBC and EOBC revealed a total of n=7 DEGs. All of these genes were upregulated and belonged to distinct superfamilies, including Cancer/Testis (CT) Antigen (MAGEA1/3, XAGE1B), Interferons/Cytokines (IFNA17, IFNB1), Chemokines (CXCL13), and Immunoglobulin (PECAM1/CD31). Notably, the upregulation of Chemokines in respect to EOBC was observed exclusively in HR+ PrBC, whereas triple-negative (TN) PrBC did not exhibit this pattern compared to the control group. Hence, the upregulation of ALOX15B, an enzyme involved in fatty acid peroxidation, was specific to TN PrBC. The immune signatures showed significant variations between PrBC and EOBC also based on TILs density and subpopulations. Indeed, the upregulation of CT genes (MAGEA1, XAGE1B) was exclusively observed in PrBC cases characterized by low TILs levels and prevalence of CD8+ or CD4+ cells. Finally, CD4+ TILs were absent or low in PrBC with upregulated Interferons, Cytokines, Chemokines, and Immunoglobulin genes, but present in cases with increased expression of CT and KLRF1 (NK cells). Conclusion: These findings highlight the heterogeneity and distinct molecular characteristics of PrBC and EOBC. The upregulation of specific immune-related gene families, such as CT and Chemokines, in different PrBC subtypes may suggest their potential role as actionable biomarkers (e.g. MAGEA, a well-known oncogene and potential immunotherapy target). The differences in immune signatures and TILs subpopulations further emphasize the importance of the immune microenvironment in PrBC biology and behavior. Future studies could delve deeper into the clinical implications of these gene expression patterns and explore their relevance in personalized treatment strategies for PrBC. Citation Format: Konstantinos Venetis, Elham Sajjadi, Chiara Frascarelli, Mariia Ivanova, Marianna D'Ercole, Concetta Blundo, Massimo Giroda, Eugenia Di Loreto, Giovanna Scarfone, Stefano Ferrero, Paolo Veronesi, Viviana Galimberti, Fedro Alessandro Peccatori, Nicola Fusco, Elena Guerini-Rocco. Decoding the immune landscape of breast cancer (BC) during pregnancy (PrBC): Impact of hormone receptors (HR) and tumor-infiltrating lymphocytes (TILs) phenotype on gene expression signatures [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 PO4-16-04.