Genetic testing for cancer risk is a vital tool for preventive care, yet its association with the uptake of evidence-based cancer screening remains unclear. This study examined the association between cancer-risk genetic testing and cancer screening uptake using data from the Health Information National Trends Survey (2017 and 2020), a nationally representative sample of US adults. We focused on the United States Preventive Services Task Force (USPSTF)-recommended screening tests for colorectal (CRC), breast, and cervical cancers. Multivariable logistic regression models, adjusted for sociodemographic and clinical factors, were used to assess the relationship between cancer screening uptake and cancer-risk genetic testing. The analysis included 6,629 respondents (mean age 48.5 years; 50.7

Introduction: Hereditary breast cancer is most commonly caused by inherited mutations in the BRCA1 or BRCA2 genes, which significantly increase the risk of breast and ovarian cancers. Methods: Denaturing High-Performance Liquid Chromatography (DHPLC) and DNA sequencing were used to analyze BRCA1 mutations, missense variants, polymorphisms, haplotypes, and large genomic rearrangements in ninety-nine African American (AA) patients from high-risk families. Sorting Intolerant From Tolerant (SIFT) analysis was applied to predict the functional impact of amino acid substitutions. Potential effects on splicing were evaluated by examining disruption of conserved exonic splicing enhancer (ESE) elements or canonical splice site sequences. Results: DHPLC and sequencing analysis identified a deleterious protein-truncating BRCA1 mutation, 5296delGAAA, in two unrelated patients diagnosed with bilateral and early-onset breast cancer, both with extensive family histories of breast and ovarian cancers. A second pathogenic variant, IVS16+6T>C, was detected in two additional patients with early-onset or bilateral breast cancer and a strong familial history. Three missense variants (Ile379Met, Glu1210Lys, Glu1794Asp), predicted to be deleterious by SIFT, were identified, including two exon 22 variants (Gln1785His and Glu1794Asp) likely to affect splicing. A rare silent variant, 884G>A (Glu255), located in an alternative exon 11 ESE, was identified in one patient and is predicted to abolish tissue-specific splicing. Multiple coding and non-coding polymorphisms were detected, and haplotype analysis revealed two predominant BRCA1 haplotypes among 64% of AA patients, suggesting population-specific allele distributions. MLPA analysis of 26 patients heterozygous for the BRCA1 exon 11 Pro871Leu polymorphism revealed a novel large deletion encompassing exons 1a, 1b, and 2, extending into the promoter region. This deletion, supported by linkage disequilibrium analysis, represents the first report of such a mutation in an AA family. Preliminary MLPA screening of an additional 40 patients and 2 cancer-free controls identified a potential exon 17 duplication in one case, warranting further investigation. Conclusion: These findings highlight the complexity and diversity of BRCA1 alterations in AA breast cancer patients and underscore the importance of comprehensive genetic screening in this population to enhance risk assessment and guide clinical management.

Abstract Introduction: Liquid biopsies offer a novel approach to diagnose, predict cancer outcomes, and monitor treatment response by analyzing tumor-derived substances. Circulating cell-free microRNAs (miRNAs) show clinical promise as biomarkers within prostate cancer (PCa) and have been implicated with PCa prognosis and outcomes. However, their potential for monitoring and assessing radiotherapy (RT) treatment response remains understudied. Understanding miRNA expression changes during RT is crucial, as they impact RT efficacy by directly affecting genes and proteins within RT-response pathways. Aim: This study aimed to profile the expression of three oncogenes, miR-17-5p, miR-20b-5p, and miR-106a-5p and to determine their association with PCa risk groups in patients receiving proton therapy (PT). Patients and Methods: Plasma was obtained from the University of Florida Health Proton Therapy Institute Outcomes Tracking Protocol biobank. Plasma was collected from men diagnosed with localized PCa without metastatic disease at three time points: prior to PT (PRE-PT), at 4 weeks following the start of PT (4WKSPD1), and at 8 weeks following the start of PT (8WKSPD1). The pilot study consisted of 38 patients, with 23 categorized as low-risk and 15 categorized as high-risk for PCa. MiRNA expression levels were evaluated using reverse transcription-polymerase chain reaction and quantified using the Livak method. Results: The study revealed a downregulation of miR-17-5p in response to PT, with median gene expression levels decreasing from 0.73 at PRE-PT to 0.587 at 8WKSPD1. Low-risk PCa patients also showed distinct miRNA expression changes with all three miRNAs (miR-17-5p, miR-20b-5p, and miR-106a-5p) downregulated from 0.953, 1.037, and 1.010 at PRE-PT to 0.398, 0.216, and 0.298 at 8WKSPD1, respectively. Statistical analysis using a Kruskal-Wallis test followed by a Dunn's post-hoc test identified significant differences (p=0.035) specifically between PRE-PT and 8WKSPD1 for miR-17-5p. Conclusion: The study revealed that PT led to a time-dependent reduction in miRNA levels, indicating a higher responsiveness in low-risk compared to high-risk PCa patients. This differential response highlights miR-17-5p, miR-20b-5p, and miR-106a-5p as potential PT response biomarkers, with clinical implications for personalizing PCa treatment. These results underscore the necessity for further validation of these miRNAs to maximize their clinical utility. Citation Format: Johnny Velasquez, Curtis Bryant, Nancy Mendenhall, Luisel Ricks-Santi. Attenuation of circulating miR-17-5p, miR-20b-5p, and miR-106a-5p in low-risk prostate cancer patients following proton therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 471.

Quadruple-negative breast cancer (QNBC) is a triple-negative breast cancer (TNBC) subtype that lacks expression of the androgen (AR) receptor. Few studies have focused on this highly aggressive breast cancer, portending worse survival rates. We aimed to determine the following: (1) QNBC’s molecular and clinical characteristics and compare them with other subtypes and (2) QNBC’s association with clinicopathological factors and prognostic markers. We performed immunohistochemical evaluations of ARs on tissue tumor microarrays from FFPE tumor blocks of invasive ductal breast carcinomas in 202 African American women. Univariate analysis was performed using the chi-square test, with survival rates calculated using Kaplan–Meier curves. Overall, 75.8% of TNBCs were AR-negative. Compared to the luminal subtypes, TNBC and QNBC tumors were likely to be a higher grade (p < 0.001); HER2+/AR- and QNBCs were also larger than the other subtypes (p < 0.001). They also expressed increasing mean levels of proteins involved in invasion, such as CD44, fascin, and vimentin, as well as decreasing the expression of proteins involved in mammary differentiation, such as GATA3 and mammaglobin. We found no association between QNBC and stage, recurrence-free survival, or overall survival rates. The high prevalence of TNBC AR-negativity in these women could explain observed worse outcomes, supporting the existence of the unique QNBC subtype.

Breast cancer (BCa) is a prevalent form of cancer in women, exhibiting varying rates and distribution across different ethnic groups. Among these groups, African American (AA) women have the highest incidence of BCa and the lowest levels of Vitamin D (VD). Numerous studies have explored the connection between variations in the VDR gene and BCa risk, particularly in different populations, but research on the AA population remains limited. Epigenetic modifications, including specific microRNAs (miRNAs), can influence gene expression without altering the genetic code and have been implicated in cancer initiation and progression. Our hypothesis suggests that VDR gene variations may increase BCa risk in AA women and that changes in miRNA expression profiles could contribute to BCa development. Using data from the 1000 Genome Project, we identified five VDR gene variants with significant frequency differences between AA and European-American (EA) populations. We genotyped 404 African American BCa cases and controls for five variants using TaqMan® assays. SNPstats assessed their association with BCa risk. The rs1544410 variant's recessive model (A/A) showed a decreased BCa risk in AA (odds ratio 0.33, 95% CI: 0.15-0.73, p-value 0.0041). Conversely, the rs2853563 variant's recessive model (A/A) was linked to an increased BCa risk (odds ratio 4.04, 95% CI: 1.49-10.95, p-value 0.0022). We investigated miRNA expression influenced by VD in HCC1806 Triple-Negative Breast Cancer (TNBC) cell lines with the A/A allele for rs2853563. nCounter® Nanostring technology assessed miRNA profiles after calcitriol treatment. Our results indicated that calcitriol treatment led to reduced expression of six miRNAs, four of which are associated with tumor suppression in the presence of the AA genotype in TNBC cell lines. These findings suggest that specific VDR genotypes could have a potential effect on the miRNAs expression which could potentially serve as markers for cell proliferation in TNBC.

Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer mortality and the incidence is projected to increase by 2030. Despite recent advances in its treatment, African Americans have a 50-60% higher incidence and 30% higher mortality rate when compared to European Americans possibly resulting from differences in socioeconomic status, access to healthcare, and genetics. Genetics plays a role in cancer predisposition, response to cancer therapeutics (pharmacogenetics), and in tumor behavior, making some genes targets for oncologic therapeutics. We hypothesize that the germline genetic differences in predisposition, drug response, and targeted therapies also impact PDAC disparities. To demonstrate the impact of genetics and pharmacogenetics on PDAC disparities, a review of the literature was performed using PubMed with variations of the following keywords: pharmacogenetics, pancreatic cancer, race, ethnicity, African, Black, toxicity, and the FDA-approved drug names: Fluoropyrimidines, Topoisomerase inhibitors, Gemcitabine, Nab-Paclitaxel, Platinum agents, Pembrolizumab, PARP-inhibitors, and NTRK fusion inhibitors. Our findings suggest that the genetic profiles of African Americans may contribute to disparities related to FDA approved chemotherapeutic response for patients with PDAC. We recommend a strong focus on improving genetic testing and participation in biobank sample donations for African Americans. In this way, we can improve our current understanding of genes that influence drug response for patients with PDAC.

Background: Diagnosed invasive breast carcinomas in African American patients are more aggressive compared with those in Caucasian patients and diagnosed at later stages of the disease with higher grade tumors. Despite advances in breast cancer systemic treatment, new prognostic and predictive biomarkers are still needed. Therefore, potential biomarkers were chosen to correlate with different subtypes, recurrence, and survival of invasive breast cancer in a cohort of African American women. Methods: Eight protein biomarkers (ER, PR, HER2, Cyclin A2, Cytokeratin 5, Vimentin, Bcl2, and Ki-67) were evaluated using tissue microarrays (TMAs) and immunohistochemistry (IHC). The IHC results from TMAs were analyzed by both supervised and unsupervised clustering methods. The predictive clusters for the supervised and unsupervised methods were compared for agreement with the empirical classification. Kappa values were used to determine the overall percent correct clusters and agreement between specific clusters. Chi-square statistics was used to examine the association between hierarchical and multinomial logistic clustering methods. Results: Five subtypes of breast tumors with distinct protein expression patterns were identified among the studied 166 breast tumors. Luminal B tumors have been distinguished from luminal A tumors by staining for cell cycle proteins Cyclin A2 and Ki-67, which promote cell proliferation. Forty-nine percent were stained positive for Cyclin A2, 39.2% positive for Ki-67, and 37% positive for both Cyclin A2 and Ki-67. The age of patients did not show any significant effect whether five (p-value= 0.576) or eight (p-value= 0.605) biomarkers were used, which indicating that age did not have any influence on the classification of the subtypes. Ninety percent of the thirty triple negative tumors were positive for Cyclin A2 or Ki-67 or both. Six-year overall survival was better for luminal A tumors (76%) than luminal B tumors (71%). Likewise, six-year relapse-free survival was better for luminal A tumors (76%) than luminal B tumors (29%). Conclusion: Discovery of molecular markers such as Cyclin A2 and Ki-67, and subtypes that are most prevalent in African Americans could lead to a better understanding of the factors contributing to higher morbidity and mortality in this group and to aid in decision-making to offer earlier treatment.

Introduction: Radiotherapy (RT) is a treatment option for men with Prostate Cancer (PCa). While minimizing damage to proximal healthy tissue, RT can still result in severe toxicities. Studies have shown that exposure to ionizing radiation leads to changes of miRNA expression at the cellular level, making cells more radioresistant or radiosensitive which could result in toxicity, recurrence, and metastatic spread. Importantly, RT induced miRNA changes have been found to be associated with RT response in clinical contexts and may serve as diagnostic tools to assess PCa risk stratification that inform precision medicine approaches. However, miRNAs have not been assessed in patients treated with proton therapy (PT), a type of particle-based RT which purports improved dose distribution and reduced toxicity. This is attributed to the proton’s unique ability to deposit most of its energy at a narrow bragg peak with minimal energy deposition beyond the peak, into surrounding organs. Because miRNAs are ubiquitous in the human body, they are stable in many environments including the bloodstream and are becoming attractive biomarkers of treatment response, including RT. Still, blood-derived biomarkers for diagnosis, prognosis, and therapy response is an emerging field and there remains a lack of standardization and normalization of sample preparation and protocol for isolating human derived miRNA from plasma. The objective is to optimize RNA isolation procedures so that it is achievable to accurately identify miRNA biomarkers in PCa patients undergoing PT. Methods: The results of 2 RNA isolation kits were compared. To assess the effectiveness of each optimization strategy performed, a number of metrics were used to quantitate and determine the quality of the RNA: fluorometry (Qubit 2.0 and 4.0), spectrophotometry (nano-drop), and qRT-PCR amplification (Taqman). Results: Fluorometry methods were not sensitive enough for RNA quantification for either kit. Of the two RNA isolation kits, Kit A outperformed Kit B in every metric output when 100 uL of plasma was initially used. Furthermore, amelioration of metric output was observed when the original starting plasma amount of 100 uL was increased to 200 uL in Kit A. Nanodrop quantities ranged from 8.85 - 32.65 ng/uL and -72.82 - 4.98 ng/uL using Kit A and Kit B, respectively. The quality (260/280 ratios) ranged from -7.65 - 3.17 and -41.65 - 6.13 for Kit A and Kit B, respectively. Taqman amplification was achieved for both kits. Conclusions: Although total RNA isolation was effectively performed, there is a need for properly optimizing miRNA detection in these blood-based biopsies. Enhancing miRNA detection to determine treatment outcomes may result in miRNA’s becoming a powerful predictive biomarker. The goal is to utilize miRNAs as a diagnostic tool for real time monitoring of individualized therapy response, detecting developing metastases, and predicting relapse. Citation Format: Johnny I. Velasquez, Andrew Bass, Moein Rajaei, Curtic Bryant, Nancy Mendenhall, Luisel Ricks-Santi. Optimization of miRNA isolation from plasma biopsies of proton therapy prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6707.

GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin, and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Markers with improved specificity and sensitivity are warranted given the high prevalence of triple negative breast cancer in the group.

Even after radiation treatment, prostate cancer (PCa) patients receiving radiotherapy (RT) are still at risk for disease progression and recurrence. Predicting outcomes associated with cancer treatment is critical to PCa survivorship given that the 5-year survival rates for local and regional stage PCa is nearly 100%. Radiogenomics is a promising field of research focused on identifying genomic markers that can provide clinically useful prognostic predictions regarding radiation response and can potentially serve as the basis for personalized RT where cancer management is tailored to fit each individual patient. Circulating cell-free (ccfDNA) DNA has been found to 1) be associated with radiation sensitivity or toxicity, 2) relapse or recurrence, and 3) risk for the development of metastases before, during or following photon RT. Proton therapy, alternative to photon therapy, is a promising treatment that can reduce excess radiation dose and, in turn, the risk for adverse events. However, few studies have been done to determine if ccfDNA can predict response in proton radiation, which purports superior dose distribution, avoiding healthy tissues, minimizing the exit dose, and potentially reducing overall toxicity. The overall aim of this study is to determine if the quantity of ccfDNA is associated with PCa risk groups. We hypothesized that PCa patients within the highest risk group have quantitatively increased levels of ccfDNA compared to those in low and intermediate risk groups. This study leveraged the University of Florida Health Proton Therapy Institute Outcomes Tracking Protocol biobank of PCa patients with plasma and serum collected before, during and after proton RT. Isolation of ccfDNA at baseline, during treatment, and following treatment was undertaken and ccfDNA quantities were compared among patients in the low, intermediate and high risk groups using ANOVA. Our results indicate that the quantity difference between baseline and day 14 of treatment (p=0.055), 2 weeks post-treatment (p=0.54), and 4 weeks post-treatment (p=0.002) was associated with risk group. There was trend towards increasing ccfDNA quantity, as risk group increased; however, there was no correlation between risk group and treatment times using the Pearson correlation. Our results were consistent in that high ccfDNA quantity was associated with PCa risk. This is the first study determining the application of ccfDNA quantity on prostate cancer outcomes in patients undergoing proton RT. Identifying the determinants of radiation-related adverse outcomes will help inform impending predictive genomic technologies and improve cancer-related outcomes and survivorship. Citation Format: Andrew Bass, Johnny Velasquez, Moein Rajaei, Curtis Bryant, Nancy Mendenhall, Luisel J. Ricks-Santi. Association of circulating cell-free DNA and prostate cancer risk groups in patients undergoing proton therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5594.

Background/Aim: The kisspeptin 1 (KISS1) gene encodes a precursor polypeptide which after proteolysis forms the kisspeptin-10 (KISS1) protein. KISS1, retains maximum physiological activity when it binds to its receptor (KISS1R), allowing KISS1 to effectively function as a suppressor of metastasis in melanomas and other types of cancer. The goal of this study was to evaluate the expression of KISS1 and KISS1R in breast carcinomas from African American (AA) women and correlate their association with clinicopathological features, including breast cancer subtypes, and outcomes. Materials and Methods: Tissue microarrays were constructed from formalin-fixed, paraffin-embedded surgical blocks from 216 AA patients. KISS1 and KISS1R expression was assessed using immunohistochemistry. Univariate analysis was used to determine the association between the expression of KISS1 and KISS1R, and clinicopathological characteristics. Pearson correlation was also determined between immunohistochemical H-scores, tumor size, and the number of positive lymph nodes. Kaplan–Meier estimates of overall and disease-free survival were plotted, and log-rank tests were performed to compare estimates among groups. Results: KISS1 protein expression was found to be higher in receptor-negative and triple-negative breast cancer (TNBC) compared to other subtypes (p<0.001). However, KISS1R expression was higher in non-TNBC tumors compared to other subtypes (p<0.001). Higher KISS1R expression was marginally negatively correlated with tumor size (p=0.077), and positively correlated with lymph-node positivity (p=0.056), and disease-free survival (p=0.092). Conclusion: Our study showed a significant inverse correlation between KISS1 and KISS1R in TNBC. This investigation implicates a role for KISS1 and KISS1R in the pathogenesis of TNBCs in AA women.

Expanded implementation of genetic sequencing has precipitously increased the discovery of germline and somatic variants. The direct benefit of identifying variants in actionable genes may lead to risk reduction strategies such as increased surveillance, prophylactic surgery, as well as lifestyle modifications to reduce morbidity and mortality. However, patients with African ancestry are more likely to receive inconclusive genetic testing results due to an increased number of variants of unknown significance decreasing the utility and impact on disease management and prevention. This study examines whole exome sequencing results from germline DNA samples in African American women with a family history of cancer including 37 cases that were diagnosed with breast cancer and 51 family members. Self-identified ancestry was validated and compared to the 1000 genomes population. The analysis of sequencing results was limited to 85 genes from three clinically available common genetic screening platforms. This target region had a total of 993 variants of which 6 (<1%) were pathogenic or likely pathogenic, 736 (74.1%) were benign, and 170 (17.1%) were classified as a variant of unknown significance. There was an average of 3.4±1.8 variants with an unknown significance per individual and 85 of 88 individuals (96.6%) harbored at least one of these in the targeted genes. Pathogenic or likely pathogenic variants were only found in 6 individuals for the BRCA1 (p.R1726fs, rs80357867), BRCA2 (p.K589fs, rs397507606 & p.L2805fs, rs397507402), RAD50 (p.E995fs, rs587780154), ATM (p.V2424G, rs28904921), or MUTYH (p.G396D, rs36053993) genes. Strategies to functionally validate the remaining variants of unknown significance, especially in understudied and hereditary cancer populations, are greatly needed to increase the clinical utility and utilization of clinical genetic screening platforms to reduce cancer incidence and mortality.

Introduction: Quadruple negative breast cancer (QNBC) is defined by the absence of androgen (AR), estrogen (ER), progesterone (PR) receptors and human epidermal growth factor (HER2) expression. This subset of triple negative breast cancer (TNBC) has been described as unique to African American (AA) women and represents about 67-90% of all TNBC. Yet, there are limited clinical and therapeutic studies focused on this new subset of breast cancer (BCa) that is highly aggressive and portends a worse survival compared to AR positive Bca subtypes. The objectives of our study were to 1) determine the molecular and clinical characteristics of QNBC and compare them with other BCa subtypes and 2) determine the association of QNBC with clinicopathological factors and prognostic markers. Materials and Methods: Tissue arrays were constructed from FFPE tumor blocks of invasive ductal breast carcinomas in 202 AAs, diagnosed at Howard University from 2000 to 2010. Two separate tissue cores of IDC represented each surgical case in the TMA and was linked to an Institutional Review Board-approved database of demographic and clinical data. Using a microtome, 5-µm sections were cut from the TMA blocks and mounted onto Superfrost Plus microscope slides. Sections were stained with a mouse monoclonal antibody against AR (Clone AR 441, DAKO). Immunohistochemistry for AR was considered positive if ≥10% of tumor cells showed nuclear staining. Bivariate analysis was performed via χ2 analysis and survival data was calculated via Kaplan-Meier curves (SPSS v28.0.0). Results: The most prevalent breast cancer subtype was luminal A (ER+ or PR+, HER2−; 43.5%), followed by TNBC (33.7%). Of the 67 TNBCs on the array, 63 had AR data; 33 (52%) of the TNBCs were AR negative. Greater than 70% of all tumors were stage I and II; and Grade 3 comprised 67.4% of the tumors. QNBC tumors were more likely to be higher grade (p<0.001) and larger in size (p=0.05) compared to other subtypes. There was also a trend for increased metastases in QNBCs (Luminal and HER2 tumors=11.2%; TNBC=13.3%; AR negative= 18.8%; and QNBC=20.8% (p=0.15)). Compared to TNBCs, QNBCs were larger (p=0.048), more likely to express markers associated invasion (Fascin, p=0.004) and reduced survival (Vimentin, p=0.014). There was a trend for increased expression of markers associated with metastases: Mammaglobin (expressed in 30.8% of TNBCs compared to 52.1% of QNBCs; p=0.17) and CD105 (expressed in 6.7% of TNBCs compared to 27.1% of QNBCs; p=0.097). There was no association between QNBC and stage, recurrence-free survival, or overall survival. Conclusion: In our study of AAs, a statistically significant association was noted between QNBC tumors and poorer prognosis. The high prevalence of AR negativity of TNBCs in AAs could explain observed worse outcomes and supports the existence of a unique subtype of Bca known as QNBC, worthy of scientific attention. Citation Format: Oluwadamilola Oladeru, Yasmine Kanaan, Tammy Naab, Luisel J. Ricks-Santi. Quadruple negative breast tumors in African American women express factors associated with worse prognosis compared to triple negative tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3682.

Mentoring continues to be a salient conversation in academia among junior and senior faculty and administrators. Mentors provide guidance and structure to junior faculty so that they can meet their academic and professional goals. Mentors also convey skills in balancing life and academic pursuits. Therefore, the purpose of this descriptive study was to provide additional insight from a training program called Leading Emerging and Diverse Scientists to Success (LEADS) regarding successful strategies and challenges of mentoring relating to lessons learned from the scholars and mentees' perspective. The LEADS program provided multiple training platforms to increase skills and knowledge regarding research to promote expertise in grant writing and submission for funding opportunities among diverse scientists. These findings reinforce the knowledge about the value of a mentor in helping define the research pathway of their mentee and underscoring the importance of mentoring.

In the original published version of this article, the figure captions for figure 3 and 4 were missing the final word: (B). The authors apologise for this error. Both the HTML and PDF versions of the article have been updated to correct the error. Annexin 2 protein expression is associated with breast cancer subtypes in African American womenBeyene et al.HeliyonFebruary 5, 2020In BriefProteins; Molecular biology; Cancer research; Pathophysiology; Epidemiology; Recurrence-free survival; Overall survival; Triple negative; Immunohistochemistry; HER2; Luminal B; Breast cancer; Annexin 2; Luminal A Full-Text PDF Open Access

Introduction: Amplification of chromosome 9p24.1 encoding PDL1, PDL2, and JAK2 (the PDJ amplicon) has been detected in 5-25% of triplenegative breast cancers (TNBC), and is associated with poor outcome and activation of the JAK/STAT pathway. Here, we have developed a robust multiplexed fluorescence in situ hybridization (FISH) assay for detection of 9p24.1 amplification, and assessed the frequency and cellular distribution of the PDJ amplicon in a cohort of African American (AA) women with TNBC. Methods: The FISH assay combines three chromosome 9 probes to simultaneously target JAK2 and PD-L1 (9p24.1, PDJ), chromosome 9q22, and the 9q34.1 regions. This enables discrimination of PDJ amplicons from whole chromosome 9p arm gains and from chromosome 9 ploidies that occur in the background of genomic instability in aneuploid cancer genomes. Fifty cells were scored for each probe and the average copy number was obtained. We defined PDJ amplification as PDJ>4, PDJ/9q22 ratio≥2, and/or PDJ/9q34.1 ratio≥2. The assay was benchmarked to array CGH of flow sorted TNBC tissue from Mayo Clinic Arizona (n=14). Tissue microarrays from TNBC PDX tumors (n=20) and from African American women with TNBC (n=87) were assessed. Results: Using selected TNBC tissue with known CGH data, the FISH assay tightly correlated with PDJ copy number in 13/14 cases. The discordant case was negative by CGH on a biopsy with low tumor content, but FISH positive on tissue section (PDJ >7.5 and a PDJ/9q22 ratio=4). Of 20 TNBC PDX tumors, 5 were amplified by FISH. Twelve of 87 (14%) of tumors had PDJ amplification by FISH, of which ten were from breast tissue and two were from lymph node. Of these 12, PDJ>4 (n=0), PDJ/9q22 ratio≥2 (n=6), and PDJ/9q34.1 ratio≥2 (n=10). Significant intratumoral variation was observed with the presence of single cells with >10 PDJ copies in 8/17 (47%) amplified and 0/90 non-amplified total cases. Conclusion: 9p24.1 (PDJ) amplification encoding JAK2, PD-L1, and PD-L2 is detected by three-color FISH in 14% of TNBC from African American women. Individual cells with ≥10 copies of PDJ was seen exclusively in 8/17 amplified cases. We identified 5 PDX tumors which may provide valuable preclinical models for the amplicon. The association of this biomarker with clinical outcome will be presented. Citation Format: Karen S. Anderson, Tammey Naab, Lori K Koslosky, Megan Anderson, Michael Lewis, Yasmine Kanaan, Ali Afsari, Luisel Ricks-Santi, Barbara A. Pockaj, Michael T Barrett. Tissue prevalence and cellular heterogeneity of 9p24.1 amplification in TNBC in African American women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-17.