Family History Of Breast Cancer Research Articles

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

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

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

Triple-Negative Breast Cancer in a Young 23-Year-Old Woman with BRCA Mutation A about A Case and Literature Review

Triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative and HER2 negative) is a particularly high-risk breast cancer which does not receive specific therapy targeting these proteins. We report the case of a 23-year-old patient diagnosed with triple-negative breast cancer of the left breast with a family history of breast cancer and carrying a BRCA1 mutation. The classification of breast cancer based on genomic data is required to allow us to optimize therapies and improve the management of breast cancer patients.

Abstract PO1-09-03: Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes

Abstract Rapid developments in cancer genetics and hereditary cancer risk assessments have enabled the identification of individuals at elevated risk for hereditary malignancies to guide enhanced cancer screening and prevention efforts. Multigene panel testing has emerged as the standard approach as emphasized in the National Comprehensive Cancer Network (NCCN) guidelines. The purpose of this study was to investigate the frequency of other pathogenic mutations identified through multigene panel testing in individuals who previously tested negative for germline BRCA1/2 and assess the clinical impact of panel testing. Patients either previously diagnosed with breast cancer or with a family history of breast or ovarian cancer that had also been seen by Oncology Genetics at a single institution and tested negative for BRCA1/2 genes but had not undergone prior multigene panel testing were invited via a letter to return for an additional genetic counseling visit to discuss multigene panel testing. Patients were also able to opt-in to a survey component of the study and received an email to fill out the Multidimensional Impact of Cancer Risk Assessment (MICRA) and Cancer Worry Scale (CWS). Surveys were completed prior to the initial genetic counseling appointment and repeated after discussion of the multigene panel test results. A total 24 women met with a genetic counselor of which 22 (92%) had a personal history of breast cancer, 1 (4%) had a family history of breast cancer, and 1 (4%) had a family history of ovarian cancer. The mean age was 52.6 years (range, 42-68) and 100% of women were Caucasian. Of the 24 women, 17 (71%) completed multigene panel testing. Of the women that underwent testing, 7 (41%) had negative results, 6 (35%) had variants of unknown significance (VUS), and 4 (24%) had a pathogenic mutation identified in another gene (CDKN2A, CHEK2, and CFTR). There was no significant change in MICRA or CWS scores after multigene panel results were reviewed in the 9 patients that completed both pre- and post-genetic testing surveys. The mean/median summary MICRA scores pre- and post-counselling were 30 (SD 12.4), median 26 (min 18, max 56), and 21.2 (SD 15.4), median 21 (min 3, max 43), respectively (p=0.19, Wilcoxon signed ranks test). The mean/median summary CWS scores pre- and post-counselling were 14.3 (SD 5), median 15 (min 7, max 24), and 13.6 (SD 2.59), median 14 (min 10, max 17), respectively (p=0.53, Wilcoxon signed ranks test). Of the 4 patients with newly identified pathogenic mutations, 2 started new screening protocols and 1 underwent a prophylactic mastectomy. In conclusion, multigene panel testing identified pathogenic mutations in a subset of individuals who previously tested negative for BRCA1/2 genes leading to changes in clinical management. The completion of multigene panel testing did not lead to a significant increase in MICRA or CWS scores. Key limitations of this study include a small sample size and an all Caucasian population. Citation Format: Devon Miller, Stephanie Pritzl, Angela Tess, Jessica Gooding, Lisa Barroilhet, Lori Dubenske, Kari Wisinski. Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes [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 PO1-09-03.

Abstract PS10-09: Development of an absolute risk prediction model for premenopausal breast cancer in an international consortium

Abstract Risk prediction models that have been developed for overall breast cancer risk are based on a limited number of premenopausal cases in individual cohorts. As some risk factors differ in their associations with pre- versus postmenopausal breast cancer, a distinct risk prediction model is needed for premenopausal breast cancer. We developed a risk prediction model for premenopausal breast cancer using 779,601 participants and 9,665 incident cases from 18 prospective studies within the Premenopausal Breast Cancer Collaborative Group (PBCCG), across North America (N=9), Europe (N=6), Australia (N=1), and Asia (N=2). Data were split, within each cohort, into training (2/3) and testing (1/3) datasets. Individual risk was assessed in five-year intervals, using variables reported at the start of the time interval. Cox proportional hazards regression was used to model risk factors in a backwards-selection method, stratified by cohort: age at menarche, age at first birth, parity, breastfeeding (months), height (cm), BMI (kg/m2), BMI at age 18, recent weight change (kg), alcohol consumption (drinks/week), first-degree family history of breast cancer, and personal history of benign breast disease. To enable the use of information from all cohorts despite differences in missing variables by design, cohorts were grouped by available variables and risk models were fit for each group. In cohorts with incomplete data, model coefficients were adjusted based on the correlation of covariates with the missing variables in the complete case dataset. Coefficients were meta-analyzed with inverse variance weighting to obtain final coefficients. Discrimination was evaluated in the testing dataset by calculation of the c-index. Work is ongoing to calibrate the model based on five-year absolute risk using GLOBOCAN continent- and age-specific incidence rates to represent baseline risk. The final model included age at menarche, parity, height, BMI, BMI at age 18, first-degree family history of breast cancer, and history of benign breast disease. Young adulthood BMI and BMI (at start of the 5-year risk interval) were associated with a decreased risk (Hazard Ratio (HR) (95% confidence interval (CI)) per 5 kg/m2 = 0.87 (0.81-0.93) and 0.90 (0.86-0.95), respectively) as was parity (HR (95% CI) = 0.92 (0.90-0.94)). Height was associated with increased risk (HR (95% CI) per 10 cm = 1.14 (1.07-1.21)), while history of benign breast disease and family history were associated with larger increases in risk (HR (95% CI) = 1.64 (1.30-2.06) and 1.76 (1.63-1.90), respectively). Model discrimination was higher than that reported for women under 50 years in existing breast cancer risk prediction models considering clinical factors (AUC (95% CI) = 0.61 (0.59-0.62)). Calibration of absolute 5-year risk is ongoing. Several factors driving risk prediction of postmenopausal breast cancer have similar influence on risk of premenopausal breast cancer, while family history has a stronger influence on premenopausal breast cancer risk. Our model demonstrates acceptable discrimination and will enable individual 5-year absolute risk prediction for premenopausal breast cancer. Citation Format: Kristen Brantley, Michael Jones, Minouk Schoemaker, Hazel Nichols, Anthony Swerdlow, Robert MacInnis, Roger Milne, Tess Clenenden, Yu Chen, Xiao-Ou Shu, Wei Zheng, Woon-Puay Koh, Jian-Min Yuan, Cari Kitahara, Martha Linet, Dale Sandler, Bernard A Rosner, Peter Kraft, A. Heather Eliassen. Development of an absolute risk prediction model for premenopausal breast cancer in an international consortium [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 PS10-09.

Abstract PO1-08-10: Impact of Oncologist-Led Genetic Counseling and Testing on Prophylactic Mastectomy Rates Among Multi-Ethnic Women with Operable Breast Cancer

Abstract Introduction: Approximately 5-10% of breast cancers are attributed to an inherited pathogenic variant (PV) in breast cancer predisposition genes, such as BRCA1 and BRCA2. Identifying women with hereditary breast cancer syndromes is critical to inform risk-appropriate screening and prevention strategies. For example, contralateral prophylactic mastectomy (CPM) has been shown to reduce the risk of new breast primaries without a demonstrated survival benefit. In a prior study, we found that women with pathogenic/likely pathogenic (P/LP) variants were over four times more likely to undergo CPM compared to those with benign/likely benign (B/LB) variants. In recent years due to expanded indications for genetic testing and social distancing during the COVID-19 pandemic, oncologist-led genetic testing and telehealth genetic counseling has gradually replaced in-person genetic counseling visits. We aimed to understand how changes in the delivery of genetic counseling and testing services impacted CPM rates among multi-ethnic women with operable breast cancer in the post COVID-19 period. Methods: We conducted a retrospective cohort study among 1,080 women diagnosed with unilateral breast cancer who underwent germline genetic testing between 2013 and 2022 at Columbia University Irving Medical Center (CUIMC) in New York, NY. The pre COVID-19 period was defined as 2013-2019 and the post COVID-19 period as 2020-2022. Demographics, including age, race/ethnicity and marital status, and clinical characteristics, such as year of diagnosis, breast cancer stage, tumor hormone receptor status, family history of breast cancer, and genetic test results, were extracted from the electronic health record (EHR). We used univariable and multivariable logistic regression analyses to estimate the odds ratio (OR) and 95% confidence interval (95% CI) associated with each variable and receipt of CPM. Results: Among 1080 evaluable women, mean age at diagnosis was 51.2 years old (SD, 12.3) with 39.6% non-Hispanic White, 27.8% Hispanic, 11.4% non-Hispanic Black, 9.0% Asian, and 12.2% multi-racial/other. Within the overall study population, 12.1% of women had P/LP variants and 21.4% had variants of unknown significance (VUS) results. Non-Hispanic Whites and Blacks had the highest frequency of P/LP variants, whereas VUS results were more common among Hispanics and Asians (see Table). Twenty-three percent of women in the study population underwent CPM. In multivariable analysis, younger age at diagnosis, more advanced stage breast cancer, family history of breast cancer, Hispanic race and P/LP results on germline genetic testing were associated with increased CPM rates. Hispanic women were over 60% more likely to undergo CPM compared to non-Hispanic White women (adjusted OR=1.63, 95% CI=1.07-2.47). No significant change in CPM rates was observed in the post-COVID era compared to the pre-COVID era. Conclusion: We aimed to understand how the transition to telehealth and oncologist-led genetic testing affected CPM rates. Although we did not observe a change in CPM rates in the post-COVID era, Hispanic women had significantly more VUS results and were over 60% more likely to undergo CPM compared to non-Hispanic White women. In future studies, we hope to improve risk communication of genetic test results and the risks and benefits of CPM, particularly in vulnerable and underserved populations. Table 1 Genetic testing results and rates of contralateral prophylactic mastectomy stratified by race/ethnicity in women diagnosed with operable breast cancer and undergoing germline genetic testing from 2013-2022 at Columbia University Irving Medical Center, New York, NY Citation Format: Alissa Michel, Kelly Luo, Vicky Ro, Matthew Fine, Meghna Trivedi, Wendy Chung, Roshni Rao, Tarsha Jones, Elana Levinson, Carrie Koval-Burt, Donna Russo, Ilana Chilton, Rita Kukafka, Katherine Crew. Impact of Oncologist-Led Genetic Counseling and Testing on Prophylactic Mastectomy Rates Among Multi-Ethnic Women with Operable 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 PO1-08-10.

Abstract PO1-08-08: Hereditary cancer genetic testing in Puerto Rican females

Abstract Background: Puerto Rico is a Caribbean Island and unincorporated United States territory with a population of approximately 3.2 million. The incidence of breast cancer in Puerto Rico is estimated at 57.5 per 100,000 females with a mortality rate of 13.0 per 100,000 females. A recent study of hereditary breast and ovarian cancer syndrome across countries in the Caribbean reported a combined positive detection rate of 14.2% using a similar multi-gene panel to the one described here. Positive rates ranged from 5.5% to 28.3% per country, but sample sizes were limited, ranged from 61 to 298 participants per country, and did not include Puerto Rico. To provide insight into the incidence of inherited tumor predisposition syndromes in less studied populations, we analyzed the demographics and germline genetic findings for a cohort of Puerto Rican females largely ascertained based on a personal and/or family history of breast cancer. Methods: This retrospective study includes 949 consecutive female individuals who underwent genetic testing at a single clinical laboratory (PreventionGenetics LLC) using a multi-gene panel test of 29 genes associated with hereditary cancer. Clinical information was obtained from health care provider-completed test requisition forms. Next Generation Sequencing (NGS) with copy number variant (CNV) detection was performed on patient-derived DNA using the Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA) and Sanger sequencing as necessary. Results: The median age at testing was 55.5 years and ranged from 19.1 to 90.0 years of age. Of the total cohort, 713 (75.1%) individuals had a personal history of breast cancer with or without additional cancer types; 43 (4.5%) individuals had non-cancerous breast findings, and 49 (5.2%) individuals had a personal history of other types of cancer(s). The remaining 144 (15.2%) individuals did not specify a personal history, but the vast majority did indicate a family history of cancer (n=133; 93.8%). Comparably, 572 (60.3%) of the individuals with a personal history of cancer or of non-cancerous breast findings reported a family history of cancer. The median age at onset for breast cancer was 53 years (n=472; range=24-89 years). A total of 90 (9.5%) individuals had a pathogenic (P) or likely pathogenic (LP) and 3 (0.3%) of individuals harbored the APC I1307K risk variant. Of the 90 individuals with positive findings, 31.1% had a P/LP variant in BRCA2, 28.0% in MUTYH, 11.8% in CHEK2, 7.5% in BRCA1, in 6.5% BRIP1, and 11.8% in ATM, CDKN2A, MSH6, NBN, PALB2, RAD51C, RAD51D, and RET. The most frequently reported pathogenic variants were MUTYH p.Gly396Asp (n=20), BRCA2 p.Glu1308* (n=16), and BRCA2 p.Asn1933Lysfs*29 (n=6). A recurrent pathogenic deletion of the upstream and exon 2 region of BRCA1 was also identified in three individuals. The indeterminate and negative rates were 36.5% (n=346) and 53.7% (n=510), respectively. Conclusion: Although the present study was limited to biological females and included individuals with broader personal and family cancer histories, the positive rate is within range of those reported for other countries in the Caribbean. Interestingly, P/LP variants have been reported to be enriched in BRCA1, BRCA2, and PALB2 across other Caribbean countries; however, this was not mirrored in the pattern of positive findings for this cohort of Puerto Rican females and may suggest a distinct background for hereditary cancer predisposition in this population. Further studies are needed to understand the landscape of germline variants in this population to ensure proper surveillance and risk mitigation is applied. Citation Format: Hannah Cox, Deborah Hartzfeld, Shawn Gessy, Christina Zaleski, Jerry Machado. Hereditary cancer genetic testing in Puerto Rican females [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 PO1-08-08.

Abstract PO3-20-08: Case Studies on Detecting Ductal Carcinoma in Situ Using Contrast-Enhanced Spectral Mammography and Predictive Indicators for Underestimation

Abstract Purpose: To introduce clinical cases of ductal carcinoma in situ (DCIS) underestimation focusing on additional benefits of contrast-enhanced spectral mammography (CESM). Background: DCIS, a noninvasive breast cancer, is often underestimated during diagnosis. Predicting which cases will upgrade to invasive cancer is crucial. CESM offers superior diagnostic performance compared to mammography and mammography with targeted ultrasound (US). Its low-energy images improve microcalcification conspicuity, enable accurate tumor extent measurement, and provide information on enhancements associated with nonmass microcalcifications. Enhanced areas on CESM can be easily compared with mammographic microcalcifications, for they are obtained during the same session. Indicators heralding DCIS underestimation 1. Detectability: underestimated DCIS is more likely to be detected on CESM and mammogram than pure DICS, whereas detection rates do not statistically differ on US and MRI. 2. Lesion type: underestimated DCIS mostly presents as enhancing mass or nonmass lesions on CESM and calcifications on low-energy conventional mammography. 3. Disease extent: on CESM, pure DCIS show smaller tumor extent than the underestimated ones. 4. CESM gray value (CGV) of the lesion on recombined image: the pure DCIS types show lower mean, standard deviation, maximum, and difference values, whereas the underestimated types demonstrate lower minimum values, and vice versa. Case 1: Screen detected pure DCIS without postsurgical upgrade in an asymptomatic 44-year-old woman. US-guided core biopsy yielded DCIS, intermediate nuclear grade with necrosis. Postsurgical pathology confirmed a 1.5 cm pure ductal carcinoma in situ, intermediate nuclear grade with necrosis. (A) US shows a 1.3 cm irregular hypoechoic mass in the right breast. (B) Routine mammography demonstrates no definite abnormality in the right breast. (C) CESM shows a 1.2 cm irregular enhancing mass in the upper central portion of right breast and CGV was 2034 AU. (D) Contrast-enhanced MR images show a 2.1 cm irregular enhancing mass in 12 o’clock direction of the right breast. Case 2: Screen detected DCIS with postsurgical upgrade to microinvasive ductal carcinoma in a 64-year-old woman with nonspecific discomfort in her right breast. US-guided core biopsy yielded DCIS, high nuclear grade with necrosis. Postsurgical pathology confirmed a 2.8 cm sized microinvasive ductal carcinoma, high nuclear grade, histologic grade 3 with necrosis. (A) US demonstrates a 1.9 cm irregular hypoechoic mass with calcifications in 9 o’clock direction 2.1 cm from the nipple in the right breast. (B) Right magnification view shows a 2.5 cm-extent segmentally distributed fine pleomorphic calcifications in the right breast. (C) CESM shows a 3 cm irregular enhancing mass with calcifications in the right breast, and CGV was 2045 AU. (D) Contrast-enhanced MR images shows a 2.3 cm irregular enhancing mass in the right breast. Case 3: Screen detected DCIS with postsurgical upgrade to invasive ductal carcinoma with DCIS in a 47-year-old woman who had a family history of breast cancer. US-guided core biopsy yielded DCIS, intermediate nuclear grade with necrosis. Postsurgical pathology confirmed a 0.2 cm invasive ductal carcinoma with 2.4 cm DCIS. (A) US demonstrates a 2.3 cm irregular hypoechoic mass in the left breast. (B) Routine mammography shows asymmetry in the upper portion of the left breast. (C) CESM shows a 3 cm enhancing mass in the left breast, and CGV of the lesion on MLO-recombined image was 2072 AU. (D) Contrast-enhanced MR image shows a 6 cm irregular enhancing mass in the upper portion of the left breast. Conclusion: CESM provides added advantages over mammography and breast US in detecting underestimated DCIS, and it is comparable to breast MRI. Key indicators to consider include detectability, enhancing lesion, larger tumor extent, higher mean CGV on CESM. Citation Format: Minji Song, Hee Jung Shin. Case Studies on Detecting Ductal Carcinoma in Situ Using Contrast-Enhanced Spectral Mammography and Predictive Indicators for Underestimation [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 PO3-20-08.

Abstract PO2-25-11: Incidence of Breast Cancer in Louisiana Compared to the United States

Abstract Aside from skin cancer, breast cancer is the most common cancer in American women. More specifically, one in eight women will develop breast cancer during their lifetime. Breast cancer is classified into subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). ER+/PR+/HER2- tumors are the most common form of breast cancer and are typically associated with risk factors including older age, nulliparity, obesity following menopause, alcohol and tobacco use, sedentary lifestyle, and hormone therapy. ER-/PR-/HER2+ tumors comprise approximately 15-20% of breast cancers and are caused by overexpression of the HER2 gene. These tumors have similar risk factors to ER+/PR+/HER2- tumors, except for age. Women with HER2+ breast cancer are likely to be younger compared to ER+PR+/HER2-. Tumors lacking hormone receptors are classified as ER-/PR-/HER2-, otherwise known as triple-negative breast cancer (TNBC). TNBC represents 10%-20% of breast cancers and carries a poorer prognosis, shorter survival, and unresponsiveness to hormone therapy compared to other forms of breast cancer. TNBC has been associated with African American race, socioeconomically deprived population, younger age at diagnosis (most frequently in women ages 40-50), more advanced disease stage, higher grade, high mitotic indices, family history of breast cancer and BRCA1 mutations. The primary aim of this study is to compare incidence of ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2- (TNBC) in Louisiana to the national population. The Louisiana Tumor Registry (LTR) was utilized to obtain state and national level data. The LTR is a participant of the National Cancer Institute’s Surveillance, Epidemiology and End Results Program, and the Centers for Disease Control and Prevention’s National Program of Cancer Registries. Our study evaluated women in Louisiana diagnosed with ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2- from 2010-2019. The populations were subdivided by age at time of diagnosis. Data was subdivided into ages 0-49, and >50. Rates were calculated per 100,00 and age-adjusted to the 2000 United States Standard Population (19 age groups - Census P25-1130). A p-value of < 0.05 indicates a significantly different rate in Louisiana comparative to the United States (SEER). Our results are as follows. Unexpectedly, Louisiana has a significantly lower rate of ER+/PR+/HER2- cancer in women ages 0-49 and ages >50 compared to the United States. Based on epidemiological risk factors, Louisiana should have a much higher rate of ER+/PR+/HER2- comparative to the United States population. Louisiana has a significantly higher rate of ER-/PR-/HER2+ cancer in women ages >50 and ER-/PR-/HER2- (TNBC) in women ages 0-49 and ages >50 compared to the United States. These findings are discordant with traditional epidemiologic studies regarding breast cancer and require further investigation. Breast Cancer Incidence Rates1 by Age from 2010-2019 in Louisiana and the United States Table 1: Breast Cancer Incidence Rates in women ages 0-49 and ages >50 from 2010-2019 in Louisiana Compared to the United States. Citation Format: Avery Daily, Julie Cupp, Krystle Trosclair. Incidence of Breast Cancer in Louisiana Compared to the United States [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 PO2-25-11.

Abstract PO2-29-03: Factors Affecting the Mammography Sensitivity and the Quality of the Breast Cancer Screening Program in the State of São Paulo, Brazil

Abstract Background: Previous researches found that false-positive mammogram results during breast cancer screening are related to age, family history of breast cancer, body mass index, and breast density. In Brazil, there is limited data available on possible factors that may influence the sensitivity of mammography and, consequently, the overall quality of the breast cancer screening program. Aims: This study aims to conduct a sensitivity analysis comparing the results of screening mammograms with diagnosis of breast cancer, taking into account factors that could impact this sensitivity. Methods: All mammogram and biopsy results in the state of São Paulo in 2013 were obtained from the Brazilian Breast Cancer Information System (SISMAMA) database. We obtained information on age (< 50, 50-59, 60-69, or 70+ years), type of lesion (solid, cyst, or calcifications), lesion size (< 10mm, 11-20mm, 21-50mm, or >50mm), lesion boundaries (defined or undefined), lesion characteristics (regular or irregular), and breast density (fatty/predominant fatty or dense/predominant dense). In addition, we evaluated the hormonal therapy usage (yes or no), radiotherapy treatment (yes or no), ethnicity (caucasian, asian, or black), education (illiterate, completed elementary school, completed high school, or completed higher education), skin type (retracted, thickened, or normal), and type of mammogram (simple or computerized). Our analysis focused on mammograms classified as BI-RADS 4, BI-RADS 5, and those with inconclusive results, which subsequently led to a biopsy for diagnosis. We conduct statistical analysis using SPSS v.29 software. To assess the agreement between mammograms and biopsy results (sensitivity), we calculated the proportion of true positive results. We compared the sensitivity across different strata of variables using the Chi-Square test and the V-Cramer measure. Results: A total of 6,064 women with BI-RADS 4, BI-RADS 5, or inconclusive mammogram results underwent biopsy procedures for breast cancer diagnosis. Among these cases, 3,414 (56.3%) were false positives, 1,765 (29.1%) were true positives, and 885 (14.6%) were inconclusive results. The sensitivity of mammographic screening was not significantly associated with ethnicity, education, type of mammogram, skin type, or previous radiotherapy. However, a higher proportion of false positive results was linked to high breast density (71.2%), irregular lesions with defined boundaries (87.5%), particularly calcifications (68.7%) smaller than 10 mm (67.5 %). True positive results, on the other hand, were associated with solid (87.1%) and irregular lesions with undefined boundaries (82.1 %), often larger than 50 mm (57.2%) in fatty breasts (82.7%). A notable proportion of inconclusive results was associated with the presence of dense/predominant dense breasts (88.4%) and irregular lesions with undefined boundaries (87%), particularly solid lesions (89.8%) ranging from 21 to 50 mm in size (60.8%). False positive and inconclusive results were more prevalent among women under 50 years old (79.8%) and those using hormonal therapy (54.8%) compared to true positives. This study has certain limitations, including the availability of data related to lesion density and morphology, as well as body mass index in the SISMAMA database, all of which can potentially impact mammography sensitivity. Furthermore, a notable limitation was a substantial number of missing values for ethnicity and education in the SISMAMA dataset. Conclusion: We identified associations between false-positive and inconclusive results on screening mammograms and factors such as age, breast density, lesion size, lesion types, and hormonal therapy. These results provide valuable information about potential factors that may affect the accuracy of mammography interpretations. Therefore, they must be taken into consideration when planning a breast cancer screening program. Citation Format: Alice Câmara, Lise Cury, Victor Filho. Factors Affecting the Mammography Sensitivity and the Quality of the Breast Cancer Screening Program in the State of São Paulo, Brazil [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 PO2-29-03.

Abstract PO4-03-09: Profile of circulating natural killer cells in stage III triple negative breast cancer before and after neoadjuvant chemotherapy

Abstract Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. The treatment for locally advanced disease is based on neoadjuvant chemotherapy and immunotherapy, with complete pathological response (pCR) serving as a predictor of disease-free survival. Although the presence of immune cell infiltration in the tumor has a favorable prognostic impact, there is a lack of predictive biomarkers for complete pathological response to neoadjuvant chemotherapy (NAC). Objective: to analyze the profile of circulating Natural Killer (NK) cells and NK subpopulations (NK FAS+ and NK PD1+) in association with the occurrence of complete pathological response after neoadjuvant chemotherapy in women with clinical stage III TNBC. Methods: This was a longitudinal prospective and translational cohort study, including women aged 18 to 60 years with stage III TNBC diagnosed between March 2015 and July 2017, with a follow-up of 24 months. A comparison control group consisted of 30 healthy women aged 18 to 60 years without prior or current cancer diagnosis and no family history of breast cancer. Peripheral blood samples were collected before NAC and before surgery. Flow cytometry was used to analyze the percentage levels of NK cells and NK subpopulations (NK FAS+ and NK PD1+). The Shapiro-Wilk test was initially applied to assess the normality of quantitative variables. The non-parametric Mann-Whitney test was used for comparison between two groups. The statistical significance level was set at p< 0.05. Overall survival (OS) was estimated using the Kaplan-Meier method. Statistical analysis was performed using GraphPad Prism v9.5.1. Results: The median age was 45 years. Stage IIIA was identified in 28% of the patients, while IIIB was observed in 72%. Regarding pathological response, 14 patients (48%) achieved pCR, while 15 patients (52%) had a non-complete pathological response (non-pCR). The 2-year OS was 86%, with no median reached. Higher percentage levels of NK cells, NK FAS+, and NK PD1+ were observed in the patient group compared to the control group, with significant differences. There was a significant increase in the percentage levels of NK cells after NAC compared to pre-NAC levels, and a reduction in NK PD1+ levels. NK cell levels were significantly higher in patients with stage IIIA compared to stage IIIB, while NK FAS+ levels were lower. NK cell and NK FAS+ subpopulation levels were significantly higher in patients who achieved pCR compared to non-pCR patients, with no difference in NK PD1+ cell levels. Conclusions: Elevated levels of circulating NK cells and NK FAS+ subpopulation collected from peripheral blood before NAC may serve as potential biomarkers for pCR in patients with TNBC. Citation Format: Luiz Jose de Barros Batista, Jurema Telles, Candice Santos, Ariani Souza, Marcelo Salgado, Leuridan Torres. Profile of circulating natural killer cells in stage III triple negative breast cancer before and after neoadjuvant chemotherapy [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 PO4-03-09.

Abstract PO5-08-01: Investigating the Link between APC I1307K Mutation and Breast Cancer in Arab Population

Abstract Background: Identifying asymptomatic individuals with an increased risk of hereditary breast cancer may significantly enhance early detection and prevention strategies and may inform treatment decision of patients who carry such variants. The APC I1307K missense mutation is known to be unrelated to conditions such as familial adenomatous polyposis (FAP), attenuated FAP, or gastric adenocarcinoma. However, individuals of Ashkenazi Jewish ancestry who carry this variant, have increase risk of colon cancer compared to the general population. The association of this variant with other cancer types, such as breast cancer, and in individuals of other ancestries, like Arabs, remains unknown. In this study, we investigate the potential association between APC gene (I1307K variant) and breast cancer risk. Method: Over a course of 18 months, all newly diagnosed patients with solid tumors were offered to participate in a universal germline genetic screening study, utilizing a standard 21-gene or an investigational 84-gene panel testing. A retrospective analysis was conducted on the 153 patients within the study group who carry the APCI1307K missense variant irrespective of cancer type. Patients were classified as meeting the criteria or not meeting the criteria of the National Comprehensive Cancer Network (NCCN) v.1.2020. Data were extracted from electronic medical records and our institutional cancer registry. Descriptive statistics test was employed. Results: Among the screened cancer patients (n=3400), 153 (4.5%) were tested positive for the APC I1307K missense mutation are included in this analysis. Median age at cancer diagnosis was 52 (range,19-80) years, and 99 (64.7%) were female. Breast cancer was the most common primary tumor (n=67, 43.8%) followed by colorectal (n=38, 24.8%), lung (n=7, 4.6%) and pancreatic cancer (n=6,3.9%). Among the 67 breast cancer patients included, 16 (23.9%) were not eligible for genetic testing as per the NCCN guidelines, and were tested as part of the universal genetic testing study. Among the patients with breast cancer, 53 (79.1%) had screening colonoscopy and 9 (17.0%) were found to have polyps (range, 1-3); 8 (88.9%) were low-grade dysplasia, while the other 44 (83.0%) had completely normal colonoscopy. On the other hand, among the 38 patients with colorectal cancer, 21 (55.3%) had tumors presenting as polyps, or exhibited concomitant polyps (range, 1-3), or displayed abnormalities in the background that were polypoid in nature. Notably, 24 (63.2%) of patients with colorectal cancer, have a family history of breast cancer. Conclusions: APC I1307K variant is unexpectedly common among our cohort of Arab patients. Individuals who carry this variant may face an elevated risk of developing breast cancer; potentially contributing to hereditary and familial cases, and such patients are at higher risk for colorectal cancer, too. Citation Format: Baha' Sharaf, Hira Bani Hani, Anas Zayed, Maha Barbar, Ahmad Hushki, Rashid Abdel-Razeq, Mohammad Titi, Reem Al-Halalsheh, Suleiman Mahafdah, Hikmat Abdel-Razeq. Investigating the Link between APC I1307K Mutation and Breast Cancer in Arab 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 PO5-08-01.

Abstract PO5-20-12: A Case of Bilateral Breast Cancer in a patient on Ocrelizumab

Abstract Background: Ocrelizumab is an anti-CD20 B cell depleting monoclonal antibodies that was FDA approved in 2017 for Relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis based on two large phase III trials (OPERA I and ORATORIO)1. In these trials, patients being treated with Ocrelizumab developed more malignancies compared to placebo. Among these cancers, breast cancer was prominent occurring in about 0.5-0.8% of the patients in the Ocrelizumab group as opposed to 0% in the placebo group. Here we present a case of bilateral breast cancer in a patient with Multiple Sclerosis (MS) treated with Ocrelizumab. Case Presentation A 66-year-old woman with a long-standing history of relapsing-remitting multiple sclerosis (MS) presented to us with concerns of bilateral masses on a screening mammogram. She was diagnosed with MS 30 years prior to presentation and was initially treated with multiple immunomodulators. However, she had progression of disease and was started on Ocrelizumab two years prior to presentation. She was up to date with her screening mammograms which had been unrevealing till now. Family history was significant for breast cancer in her grandmother in her 70s. Her annual mammogram screening showed bilateral irregular masses. A subsequent right breast ultrasound showed three breast masses(1cm, 0.5cm and 0.5cm respectively) and her left breast showed a 0.5 cm mass. Biopsy from the right breast showed invasive ductal and lobular carcinoma(ER+, PR+, HER2-) and that from the left breast showed invasive lobular carcinoma(ER+, PR+, HER2-).She underwent bilateral mastectomies and sentinel lymph node biopsies. The surgical margins and lymph nodes were negative for malignancy hence radiation was not warranted. Genetic testing revealed one pathogenic variant in MSH3 but was negative for BRCA1 and 2. Since her Oncotype dx score was low, adjuvant chemotherapy was not offered. She was started on aromatase inhibitor and her Ocrelizumab was permanently discontinued. Discussion Ocrelizumab is one of the immunomodulator drugs for MS with a probable mechanism being B-cell depletion. The mechanism of how it causes breast cancer is unknown. However, suggested theory is that B cell inhibitors can increase the risk of breast cancer by inhibiting the potentially protective role of the B cells. The B cells are thought to play a role in the tumor micro-environments as antigen presenting cells and activators of natural killer and cytolytic T cells targeted toward lysis of tumors. Also, B cell presence, specifically CD20 B cells, is linked to a better prognosis in breast cancer. One study has also pointed out the importance of timing of anti-b cell therapy in relation to cancer morbidity. Treatment of mice with Anti-CD20 therapy prior to tumor challenge did not result in cancer metastasis. Whereas post tumor challenge, there was increased tumor cell survival and metastasis. Our patient although had a family history of breast cancer, did not have a genetic mutation that could have contributed to her breast cancer. Her breast cancer developed after her therapy with Ocrelizumab hence raising suspicion for causation. With rise in the use of immunosuppressive therapies, further data is needed to delineate pathogenesis. Women with MS have lower all-cause survival after breast cancer diagnosis than women without MS. Hence it is important to identify any risk factors or therapies that might be associated with increased risk of cancer. Citation Format: Kriti Mehra, Mohamad Hejazi. A Case of Bilateral Breast Cancer in a patient on Ocrelizumab [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 PO5-20-12.

Abstract PO5-23-05: The Impact of Bi-Annual Diagnostic Imaging on Detecting Ipsilateral Breast Recurrence in Patients Undergoing Breast Conserving Surgery for Breast Cancer

Abstract Introduction: Breast conserving surgery (BCS) represents the preferred option for surgical treatment for a majority of patients with early-stage breast cancer who are eligible for this approach. When compared with mastectomy approaches, BCS provides patients with equivalent survival while preserving the affected breast. It is necessary to achieve clear surgical margins as positive lumpectomy margins are associated with an increased risk for ipsilateral breast tumor recurrence. With advances in imaging techniques, as well as effective systemic therapy and contemporary radiation therapy, local recurrence after BCS has decreased and overall survival for patients has improved. Retrospective studies have quantified the recurrence rate in unifocal breast cancer as 8 - 15% at 20 years. The NCCN recommends annual mammography at least 6 months after post-lumpectomy radiation therapy, but there is little data regarding more frequent surveillance after lumpectomy in the early post-operative setting. The purpose of this study was to evaluate the impact of short interval surveillance mammography on the detection of early in-breast recurrence in patients undergoing BCS. Methods: Our IRB-approved Breast Cancer Database was queried for patients enrolled from 11/2009 to 6/2023 who underwent breast conservation surgery for a diagnosis of in situ or invasive breast cancer in this retrospective analysis. Per our institutional protocol, patients were recommended to undergo diagnostic mammography of the treated breast(s) every 6 months for 2 years after BCS. After the initial 2 year period, bilateral mammography was performed annually in the absence of other indications. Additional supplemental imaging such as breast ultrasound and MRI were performed at physician discretion and based on patient risk and breast density. Variables of interest included the presence of pathogenic germline mutations, family history of breast cancer, and disease characteristics. Our primary endpoint was ipsilateral breast tumor recurrence. Results: Of 2491 patients who underwent breast conservation surgery for in situ or invasive breast cancer, 191 (7.7%) developed recurrent disease, including ipsilateral and contralateral recurrence, and distant disease, in the study period. A total of 83 (3.2%) patients developed ipsilateral breast recurrence during the entire study period. Of those, 19 (22.9%) were detected within the first two years after surgery. Six of the 19 patients (31.6%) had their recurrences detected on yearly diagnostic mammography while 6 (31.6%) patients had their recurrences detected on interval 6-month unilateral diagnostic imaging. In both groups, 5/6 recurrences were invasive disease after an original diagnosis of invasive cancer, and the remaining patient had recurrent DCIS. The remaining 7/19 patients (36.8%) had their ipsilateral recurrences detected on palpation or other diagnostic imaging. In this group as well, there was one case of recurrent DCIS, with the remaining 6 cases representing recurrent invasive cancer. Of the 19 patients with ipsilateral recurrences, none had pathogenic germline mutations. 4 of the 19 patients (21%) had positive margins after their initial lumpectomy surgery with re- excisions required to achieve clear margins. Conclusion: Interval diagnostic surveillance imaging every 6 months after breast conserving surgery identified almost one-third of the ipsilateral breast tumor recurrences that occurred within the first 2 years after surgery in our population. While our numbers are small, the relationship of re-excision lumpectomy surgery to subsequent risk for local recurrence has been described by others, and bears further study. Particularly in view of our observation that the majority of in-breast recurrences were invasive, our data supports the practice of more frequent imaging follow up in the first 2 years after breast conserving surgery. Citation Format: Pabel Miah, Laura Fiedler, Anthony Baez, Athanasios Sevdalis, Alyssa Marmer, Charles DiMaggio, Linda Pak, Richard Shapiro, Karen Hiotis, Deborah Axelrod, Amber Guth, Freya Schnabel. The Impact of Bi-Annual Diagnostic Imaging on Detecting Ipsilateral Breast Recurrence in Patients Undergoing Breast Conserving Surgery for 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 PO5-23-05.

Abstract PO5-27-04: The epidemiological profile and lifestyle of non-village indigenous women from Amazonas, Brazil and the likely impact on breast cancer mortality

Abstract Introduction: The high and growing incidence of breast cancer is a reality in almost every continent. However, the low mortality from this neoplasm among indigenous people of Amazonas, Brazil, is an intriguing fact (table 1). Inspite having a lower life expectancy at birth, the magnitude of low mortality is even greater. Indigenous women have gradually integrated into the non-indigenous community, and the reality of low mortality from breast cancer may be at risk of not existing in the future if the justification is in their reproductive epidemiological profile and lifestyle. Objective: This work seeks to find variables that can justify the fact that indigenous women from the Amazon region die less from breast cancer when compared to non-indigenous women. To achieve this, we evaluated reproductive epidemiological factors and lifestyle in non-village indigenous women and compared them with the same data in non-indigenous women. Methods: This is a cross-sectional study consisting of a convenience sample in which all indigenous people treated at the Mastology Outpatient Clinic of the Getúlio Vargas University Hospital of the Federal University of Amazonas were invited to participate from September 2020 to March 2023. There were 126 women: 39 non-village indigenous people who have lived in Manaus for more than 5 years and are integrated into society, 47 non-village indigenous people who live in riverside and interior populations of Amazonas - or in Manaus for less than 5 years - and 40 non-indigenous individuals. A questionnaire in interview format was administered with the objective of evaluating epidemiological and reproductive aspects such as age, education, BMI, menarche, parity, age at first pregnancy, breastfeeding, use of hormonal medications as well as lifestyle factors including smoking, alcohol consumption, dietary habits, physical activity, use of herbs, roots and seeds for therapeutic purposes and practice of religious devotional habits. Results: There was no difference in age, BMI, education, menarche and parity between the interviewed patients, nor in the assessment of the consumption of milk, sugar, fruits, vegetables and legumes, smoking habits, alcohol intake or physical activity between the groups. Indigenous women living in Manaus had a lower age at first pregnancy when compared to non-indigenous women. The variable “breastfeeding time” did not reach statistical significance but demonstrated a very close index (p 0.058) and a tendency to suggest that indigenous people, regardless of their place of residence, breastfeed for a longer duration. Non-indigenous women had a longer history of using hormonal medications when compared to indigenous women living in Manaus. Regarding meat consumption habits, indigenous women living in riverside and interior populations showed higher percentages of sporadic consumption of beef, sporadic consumption of wild animals, and daily consumption of white meat compared to non-indigenous people. On the other hand, non-indigenous women had a higher percentage of never having consumed wild animal meat when compared to the two other groups. Among indigenous women from riverside populations, there was a lower percentage of religious practices. The consumption of herbs, roots or seeds for therapeutic purposes was more commonly observed among indigenous people living in Manaus when compared to non-indigenous people. Conclusion: No epidemiological or lifestyle variables were found in both groups of indigenous people that justify the low mortality from breast cancer in these women. However, although the variable “breastfeeding time” did not reach statistical significance, it demonstrated a very close index (p 0.058) and a tendency to suggest that indigenous people, regardless of their place of residence, breastfeed for a longer duration. This could be a potential explanation for the low mortality from this disease among indigenous women. Table 1: Participation of breast cancer deaths in the total number of deaths in women over 20 years of age in the State of Amazonas Source: prepared by researchers Table 2 - Menarch, parity (childbirth and miscarage), breastfeed, Family history of breast cancer, image exam Table 3: Red and white meat consumption Citation Format: Maria Riselda Vinhote Da Silva, Lilian Cristina De Souza Guimarães, Afonso Nazário, Mariana Guimaraes De Oliveira Castro. The epidemiological profile and lifestyle of non-village indigenous women from Amazonas, Brazil and the likely impact on breast cancer mortality [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 PO5-27-04.

Abstract PO5-17-06: Prevalence of BRCA Mutations: A Predictive Model in a High-Risk Population of BC Patients at a Tertiary Care Center

Abstract Background: Breast cancer (BC) is a prevalent cancer in Saudi Arabia, with the majority of cases being sporadic. However, 25-30% of cases are associated with hereditary factors. Germline BRCA mutations are the most common mutations linked to hereditary BC predisposition syndromes, with a reported frequency of up to 11% in Saudi Arabia. Methods: This retrospective cohort study was conducted at a single institution in Saudi Arabia. Medical records of BC cases were reviewed where BRCA testing was performed, typically in patients with triple negative BC, hormone-positive (HR+) BC in younger premenopausal patients under the age of 45, or those with a personal or family history of BC. Patients meeting these criteria were diagnosed and treated at a tertiary care center in Saudi Arabia,between 2018 and 2021. The association between BRCA positivity and proposed risk factors was evaluated using chi-square analysis. Multivariate analysis was performed using logistic regression to assess the association between independent significant risk factors and BRACA+. Results: 482 cases of breast cancer were reviewed, with 412 testing negative for mutations and an overall BRCA positivity rate of 13.7%. Among BRCA positive patients, 62% had a positive family history (p-value < 0.001), and they tended to be younger, with a median age of 38 compared to BRCA negative patients with a median age of 42 (p-value = 0.01). Of the 469 female patients, 62 (13%) were BRCA positive, and of the 12 male patients, 3 (25%) were BRCA positive. Among the BRCA positive patients, 73% had BRCA1 mutations, and 26% had BRCA2 mutations. No patients with lobular BC tested positive for BRCA mutations. The odds ratio for BRCA positivity in triple negative BC was 3.6 (95% CI 2.1-6.2, p-value < 0.001). The odds ratio for BRCA positivity in HR+ cases was 2.5 (95% CI 1.4-4.2, p-value = 0.001). In HR+ cases, 4.6% had BRCA1 mutations, and 5% had BRCA2 mutations. In ER- cases, 20% had BRCA1 mutations, and 1.2% had BRCA2 mutations. Multivariate analysis revealed that increasing the age of diagnosis by one year reduced the chance of having BRCA positivity by 5% (p-value = 0.009). Having a positive family history increased the risk of BRCA positivity with an OR of 8 (95% CI 4-15.8, p-value < 0.001), and triple negative BC increased the risk of BRCA positivity with an OR of 4.1 (CI 2.2-7.5, p-value < 0.001). The model performance was evaluated using an AUC of 0.80. Conclusion: This study highlights the high prevalence of BRCA mutations in a high-risk population of BC patients. The proposed predictive model identified younger age, triple negativity, and a positive family history as independent predictors, with an AUC of 0.8. The study's predictive model suggest that these factors may be useful in identifying patients who are at increased risk of carrying BRCA mutations and could benefit from genetic counseling and testing. Citation Format: Kausar Suleman, Khalid Al-Khatib, Emaan Haque, Tusneem El Hassan, Abdullah Al Suwaidan, Sabah Alaklabi, Taher Twegieri, Adhar AlSayed, Dahish Ajarim, Meshari Al Zahrani, Syed Saad Akhtar, Osama Al Malik, Amal Al Hefdhi, Wafa Khayal, Sitah Al Zughaibi, Asma Tulbah. Prevalence of BRCA Mutations: A Predictive Model in a High-Risk Population of BC Patients at a Tertiary Care Center [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 PO5-17-06.

Abstract PO2-09-08: Biological and non-biological predictors of breast cancer disease-free survival among young Black females

Abstract Introduction: Young Black females bear a disproportionate burden of breast cancer (BC) deaths compared to White females yet remain underrepresented in clinical studies. We sought to discover predictors of disease-free survival (DFS) in a cohort of young Black females with BC. Methods: Black females diagnosed with invasive BC ≤ age 50 from 2005 to 2016 were recruited through the Florida and Tennessee state cancer registries. Participants were asked to complete a questionnaire, medical records release, and tissue/tumor release. Saliva was also requested for germline DNA extraction. For the primary outcome of BC DFS, univariate analyses were conducted using the following variables: proportion of West African ancestry, RNA expression based on PAM50 analyses, body mass index (BMI), social determinants of health (i.e., employment and insurance), immunohistochemistry (IHC) subtype, treatment category (i.e., chemotherapy, radiation, and surgery), and BC family history. Multivariate analyses were conducted using backward selection among these variables to analyze in the reduced model. Results: Of 701 consented, 687 participants with early-stage disease were included in the analysis; 14 participants with stage 4 disease at diagnosis were excluded. Among the 687 participants, the median age at diagnosis was 44, 28% had triple-negative breast cancer (TNBC), 13% were deceased, and 5% had recurrent disease. Clinically, participants with TNBC and lymph node involvement had worse BC DFS (p=0.001 and p=0.0002, respectively). Socio-economically, full-time employement was associated with higher BC DFS (p=0.0003). Among those for whom global ancestry data were available (n=551), multivariate analysis showed an association between increased percent of West African ancestry and worse BC DFS with HRIQR=1.23*, which approached significance (p=0.085). Additional subgroup analyses among those with hormone receptor-positive (HR+) (estrogen and/or progesterone receptor positive) BC (n=431) showed that participants with private insurance had better BC DFS (HR=0.45; p=0.05), while those with lymph node involvement had worse BC DFS (HR=2.07; p=0.001). Among HR+ participants with available ancestry data (n=349), worse BC DFS was associated with increased West African ancestry (p=0.05) and lymph node involvement (p=0.08). When ancestry was included in the model, private insurance was no longer associated with BC DFS in this HR+ subgroup (p=0.31). Other predictors analyzed did not reach statistical significance. Conclusion: Our findings confirm prior established adverse predictors of BC DFS, such as TNBC with lymph node involvement and the protective effect of full-time employment. We also found a novel association with West African ancestry among patients with HR+ breast cancer. Although further large-scale studies are needed, results from this cohort of young Black females with BC and highlight the critical need to support research to understand biological and non-biological factors contributing to BC DFS and develop targeted strategies to improve survival outcomes. * HRIQR is the ratio of hazard rates corresponding to upper and lower quartiles of percent West African (interquartile range (IQR): 70.0%-80.8%). Citation Format: Sonya Reid, Run Fan, Lindsay Venton, Anne Weidner, Ann Tezak, Mya Roberson, Susan Vadaparampil, Xuefeng Wang, Sean Yoder, Marilin Rosa, Jibril Hirbo, Jennifer Whisenant, Jennifer Pietenpol, Sheila Rajagopal, Brian Lehmann, Fei Ye, Tuya Pal. Biological and non-biological predictors of breast cancer disease-free survival among young Black females [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 PO2-09-08.

Abstract PO1-20-11: Delay in Diagnosis of Locally Advanced Breast Cancer during Lactation “Case Report”

Abstract A 38-year-old breastfeeding female with no family history of breast or gynecological cancer presented to her PCP with a 4-month history of galactorrhea and enlarged left-sided breast mass. On physical exam, a 4-inch round complex, nonmobile, non-tender mass in the left breast and bloody-to-pink discharge from the nipple was present on the exam. Diagnostic mammogram and US revealed BIRADS 5, microcalcifications consistent with DCIS, 4-cm mass, with a positive lymph node (LN), and needle core biopsy of both breast and LN, showed DCIS and metastatic carcinoma, respectively. Further workup did not show distant or skeletal metastatic disease. Therefore, a diagnosis was made, and the patient was provided a clinical-stage cT3, cN2, cM0, ER+, PR-, and HER2+. The patient completed neoadjuvant therapy with TCHP and underwent a left lumpectomy with sentinel LN biopsy. Additionally, pathology diagnosis showed scant residual DCIS (10mm) and no metastatic disease in the LN. After that, the patient completed adjuvant radiotherapy and was placed on adjuvant therapy with trastuzumab and pertuzumab. In conclusion, any breast abnormality reported by a pregnant or breastfeeding woman should not be neglected and assumed that it is a regular and physiological change until proven otherwise. Future proposals include guidelines for managing abnormal breast findings during pregnancy. Citation Format: Jesus Flores Banda, Kavitha Donthireddy. Delay in Diagnosis of Locally Advanced Breast Cancer during Lactation “Case Report” [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 PO1-20-11.

Abstract PO4-09-08: Perceptions and Experiences of Black Women on Family History Sharing and Genetic Testing for Hereditary Breast and Ovarian Cancer

Abstract Black women experience significant disparities in morbidity and mortality related to hereditary breast and ovarian cancer (HBOC). Early identification of women with HBOC is essential for proactive screening and timely diagnosis. However, evidence suggests that Black women receive genetic testing for HBOC at lower rates than their White counterparts. We conducted in-depth qualitative interviews with 107 Black women with a personal or family history of breast or ovarian cancer, to understand their perceptions of their familial risk of HBOC and interest in genetic testing. In phase 1 of this study, participants were recruited from the networks of patient support organizations and historically Black sororities representing mostly highly educated and well insured patients. In phase 2, participants were recruited from a family medicine safety net clinic in Jacksonville, FL for socioeconomic diversity. Participants in both cohorts frequently expressed a lack of awareness about their family cancer history and identified many barriers to family disclosure of a cancer diagnosis. These include a culture of silence around medical issues and a belief that personal difficulties should be kept to oneself. Practical and cultural barriers to family history sharing were magnified among those with lower socioeconomic status. Many participants in both cohorts indicated a strong desire to understand their own risk of HBOC. They also expressed interested in genetic testing to proactively mitigate risk to themselves and future generations. Understanding of the potential relevance of HBOC testing to one’s personal health and post-test actionability was variable across both groups, although perceptions of genetic testing were generally favorable. These findings suggest that culturally tailored educational materials and alternative clinical modalities to collect family health history may be beneficial to improve timely identification of Black women who meet NCCN Guidelines for HBOC testing. Specifically, greater attention should be given to addressing barriers that led to underestimation of HBOC risk among patients experiencing disparities driven by adverse social determinants of health. Citation Format: Kirsten Riggan, Jane Yap, Ewan Cobran, Michele Halyard, Sarah James, Marion Kelly, Daphne Phillips, Megan Allyse. Perceptions and Experiences of Black Women on Family History Sharing and Genetic Testing for Hereditary Breast and Ovarian 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 PO4-09-08.

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

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