Prevalence Of Triple Negative Breast Cancer Research Articles

Racial disparities among triple negative breast cancer clinical trial enrollees between 2010-2023.

1093 Background: Despite the social construct of race lacking biological significance, it plays a significant role in health disparities and necessitates examination to address social stratification and health inequities. Not reporting race in medical research neglects the reality of social stratification, injustices, and implications for population health. Additionally, excluding racial demographic data from research publications may conceal health disparities. This study focuses on Triple Negative Breast Cancer (TNBC) clinical trials, aiming to meta-analyze the inclusion of racial data and assess racial representation. Methods: A meta-analysis of 81 completed TNBC trials (2011-2023) from ClinicalTrials.gov was conducted. Demographic data on race and sex were extracted and analyzed using Microsoft Excel. Two independent reviewers extracted study-level data for a random-effects analysis. The primary outcome was identifying the prevalence of studies lacking racial data. The secondary outcomes are the prevalence of each racial category (White, Black, Asian, Hispanic/Latino, and Combined Other) among all TNBC clinical trials that reported demographic information. The Combined Other category includes American Indian, Native Hawaiian, more than one race, and unknown/unreported. Results: Of 81 trials, 29.63% did not report racial data. The remaining 57 trials (8,196 participants) revealed 73.98% White, 10.29% Asian, 7.85% Black, 8.02% Hispanic/Latino, and 4.12% "combined other" participants. U.S.-based trials (36 studies, 3,348 participants) showed 77.96% White, 12.03% Black, 4.51% Asian, and 4.96% Hispanic/Latino participants. Moreover, we conducted a comparative analysis between the racial distribution in U.S. clinical trials and the prevalence of TNBC in the U.S. population, utilizing the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Public Use Datasets (2010-2019). The analysis revealed a significant discrepancy with White (p<.001) participants being overrepresented, and Black (p<.001), Asian (p<.001), Hispanic/Latino (p<.001), American Indian (p<.001), more than one race (p<.02), and Other/Unknown (p<.001) populations being underrepresented. Conclusions: Globally, 29.63% of TNBC trials did not report racial data, raising concerns about generalizability. U.S.-based studies exhibited overrepresentation of White participants and underrepresentation of Black, Asian, Hispanic/Latino, American Indian, Native Hawaiian, and other categories. Notably, Black and Hispanic/Latino individuals, comprising a substantial portion of TNBC patients, were underrepresented. These findings underscore racial/ethnic disparities in breast cancer trial participation, warranting further investigation into recruitment barriers for equitable participation.

Intercontinental Comparison of Immunohistochemical Subtypes Among Individuals With Breast Cancer in South-East Asia and South America: A Scoping Systematic Review and Meta-Analysis of Observational Studies.

Breast cancer (BC) remains a significant global concern, particularly among developing countries in South-East Asia (SEA) and South America (SA). The socioeconomic burdens of oncologic care in those countries were often originated from limited accessibility on attainable therapeutic options and reliability on identifying essential information of cancer cells, i.e., immunohistochemical (IHC) subtyping to determine suitable approaches. The triple-negative breast cancer (TNBC) is among the most aggressive category in breast malignancy, therefore, requiring more specific molecular pathway blocking to exhaust the cells. However, large-scale epidemiological investigation on its rate among BC remains unavailable to date. This study aimed to describe the prevalence of TNBC in the SEA and SA continents since it may guide the future direction of oncologic research and trials. This review focuses on observational studies from the SEA and SA continents from the last decade. Each study represents its country or cities, period of observation, population size, and the TNBC-BC rate as the main outcomes. Therefore, we may also limit the reporting bias originated from same-patient data on the specific occasions. The analysis will be derived to SEA-SA comparison, plus SEA/SA-specific session as processed in Comprehensive Meta-Analysis (CMA) version 3.0. The statistical analysis will be performed in random effects model (REM) within 95% confidence interval (CI). From 46 studies included in the final analysis with a total enlisted population of 34,346 unique individuals with BC, the TNBC rate was higher in the SEA compared to the SA region (19.3% vs. 15.7%; P < 0.05 in 95% CI), with the highest prevalence observed in Vietnam (22.4%) and Peru (17.8%), if it was restricted on countries with two or more studies. Interestingly, both Laos and Argentina possessed significant differences compared to other countries within their respective continents, with the highest and lowest TNBC rates (P < 0.05). The IHC characteristics in SEA differ from those in the SA continent as mainly represented by TNBC prevalence, possibly shaping the course of future trials in the respective region based on IHC expressivity status.

Comparative analysis of breast cancer characteristics in young premenopausal and postmenopausal women in Ghana

Breast cancer is increasingly common among young women in Ghana. BCa is heterogeneous with unique traits that impact causes, prognostic, and predictive outcomes of patients before and after menopause. However, limited evidence exists on differences between young premenopausal (YPM) and postmenopausal cases in Ghana. This study compared breast tumour characteristics between YPM women (under 35 years) and postmenopausal women. We conducted a prospective cross-sectional study involving 140 BCa-diagnosed women at the Breast Care Clinic of Komfo Anokye Teaching Hospital (KATH), Kumasi from November 2019 to June 2021. Thirty-one (22.1%) of participants were YPM and 109 (77.9%) were postmenopausal. The median ages for YPM and postmenopausal were 32.0 (range: 25.0–35.0) and 57.0 (48.0–86.0) respectively. Invasive carcinoma was the most common histological type (97.1%). Left tumour location was the most frequent in both groups (51.6% for YPM and 51.8% for postmenopausal). Lumps detected were frequently in the outer upper quadrant in both groups (61.3% and 56.0%). The majority of the YPM women (80.7%) and postmenopausal women (87.0%) had stage III and IV diseases. Most YPM (64.5%) and postmenopausal women (64.4%) exhibited triple-negative breast cancer (TNBC). Both YPM 13 (56.6%) and postmenopausal participants 40 (56.3%) exhibited a predominantly partial response to neo-adjuvant chemotherapy but YPM women (21.7%) experienced disease progression than the postmenopausal women (12.7%). The study highlights consistent tumour characteristics and advanced clinical stages at diagnosis in both groups with a higher prevalence of TNBC. TNBC and HER2+ subtypes respond better to Anthracycline-based neoadjuvant chemotherapy. Establishing Breast Care Clinics in district and regional hospitals for early detection is crucial and further studies are warranted to understand the higher TNBC prevalence in black Africans and re-evaluate breast education programs to address the persistently late presentations.

Risk factors and survival of triple-negative breast cancer among breast cancer patients: Ten-year cross-sectional study in the southwestern Iranian population.

Breast cancer results from genetic and epigenetic mutations, contributing significantly to cancer-related morbidity and mortality. This study aimed to determine the prevalence and survival rates of triple-negative breast cancer (TNBC) among breast cancer patients in southwestern Iran over a ten-year period. This retrospective cross-sectional study aims to assess prognostic factors associated with survival in women diagnosed with breast cancer in Iran's southwestern region over a ten-year period (2007-2017). Data were collected from patients who visited the Clinical Oncology Department at Golestan Hospital in Ahvaz (the breast cancer center of the Southwestern country). The study enrolled women diagnosed with TNBC using a census method and data from medical records. The primary outcome (survival rates) and secondary outcomes (demographic data, diagnostic stages, and three receptors estrogen receptors [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2] status) were collected. Breast cancer was diagnosed in 2641 women over ten years; TNBC was diagnosed in 227 individuals (8.59%). Statistical analysis revealed a significant correlation between negative ER status and TNBC (p > 0.05). Furthermore, the prevalence of TNBC differed significantly from that of other types of breast cancer (p = 0.0001). The variables of age, HER2, PR, and TNBC grade did not differ significantly (p > 0.05). The overall disease-free survival rate over 5 years was 88.1%, while the rate for individuals without recurrence was 77.97%. This study highlights a differentially low incidence of TNBC in the southwestern part of Iran when compared to other regions; genetic or epigenetic influences may explain this discrepancy. ER-negative status is a crucial prognostic indicator in diagnosing TNBC. The incidence of this disease is expected to rise by 100% in 2 years and 77.97% in 5 years.

Abstract C118: Racial disparities in insurance coverage for supplemental breast cancer screening

Abstract Introduction and Purpose: Women with dense breasts have increased risk both for developing breast cancer and false-negative mammograms. Supplemental screening with breast MRI has been shown to shown to significantly increase cancer detection among women with dense breasts. In May 2023, Pennsylvania (PA) mandated insurance coverage of one supplemental screening study (breast MRI or ultrasound ) annually for women with dense breasts. Prior research suggests that Black women have lower breast density on average than white women based on subjective grading from the American College of Radiology Breast Imaging and Reporting Data System (BI-RADS), partially due to larger average breast size and higher body mass index (BMI) than white women. The purpose of this study was to estimate the potential impact of this supplemental screening law on different patient populations in a large health system. Methods: Women without prior breast cancer or known BRCA1/2 mutations who underwent mammographic screening at a large PA health system from April 2015-December 2017and completed a risk factor questionnaire were included (N=83,579). Under PA law, women must have either heterogeneously dense breasts plus &amp;gt;20% lifetime risk of breast cancer or extremely dense breasts to be eligible for insurance coverage for supplemental screening, both of which involve subjectively graded breast measurements. Breast cancer risk for each patient was estimated using the Gail model. The cancer detection rate (CDR) for mammographic screening was calculated as the number of cancers diagnosed within one year of a positive mammographic screen; the interval cancer rate was calculated as the number of cancers diagnosed within one year of a non-actionable screening mammogram per 1000 women. Logistic regression was used to calculate the odds of eligibility adjusted for age and BMI. Results: Black women were less likely to have extremely or heterogeneously dense breasts than white women (23.7% vs. 45.0%, p&amp;lt;0.001). Under PA law, 2.5% of Black women and 9.9% of white women would qualify for insurance coverage for supplemental screening (p&amp;lt;0.001). Only 0.2% of Black women and 2.3% of white women had heterogeneously dense breasts and &amp;gt;20% lifetime risk. Black women were more likely to have triple-negative breast cancer (TNBC) than white women (p&amp;lt;0.001). After adjusting for age and BMI, Black women remained 54% less likely to be eligible for supplemental screening than white women (OR=0.46, 95% 0.42-0.51, p&amp;lt;0.001).Conclusions: Black women are less likely to qualify for insurance coverage for supplemental breast cancer screening than white women under PA law. Given that Black women have lower prevalence of subjectively graded dense breasts and higher prevalence of TNBC, the new supplemental screening law is unlikely to meaningfully reduce racial disparities in breast cancer mortality. Methods to better assess breast cancer risk among Black women, particularly the risk of TNBC, are urgently needed to identify Black women that may benefit from supplemental screening. Citation Format: Mattia A. Mahmoud, Sarah Ehsan, Oluwadamilola M. Fayanju, Susan M. Domchek, Katherine L. Nathanson, Despina Kontos, Emily F. Conant, Anne Marie McCarthy. Racial disparities in insurance coverage for supplemental breast cancer screening [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C118.

A Study on the Factors and Prediction Model of Triple-Negative Breast Cancer for Public Health Promotion.

This study was conducted to identify the risk causes and predictive models based on the clinical features of patients with breast cancer classified as triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBCs) using Korean cancer statistics. A total of 2045 cases that underwent three types of hormone receptor tests were obtained from Korean cancer data in 2016. Research data were analyzed with the software SPSS Ver. 26.0. TNBC and non-TNBCs accounted for 12.4% and 87.6% of the data, respectively. Tubular and lobular tumors occurred most frequently in the external quadrant of the breast (C50.4-C50.5; 43.1%). Compared to non-TNBCs, the incidence of TNBC was the most common in patients under the age of 39 (19.5%), followed by those over the age of 70 (17.3%). Tumors larger than 2 cm accounted for 16.0%, which was higher than the number of tumors smaller than 2 cm. Cases in stage IV cancer represented 21.7% of the data. Additionally, 21.0% of the patients were in the SEER stage of distant metastasis, which was the most prevalent SEER (surveillance, epidemiology, and end outcomes) stage. Neoadjuvant therapy was administered more frequently, with a rate of 24.1%. In the logistic regression and decision-making tree model, the variables that affected TNBC were age, differentiation grade, and neoadjuvant therapy. The predictive accuracies of logistic regression and decision-making tree models were 87.8% and 87.6%, respectively. In a decision-marking tree model, the differentiation grades of TNBC affect neoadjuvant therapy, and neoadjuvant therapy affects the cancer stage. Therefore, in order to promote the health of breast cancer patients, it is urgent to apply an intensive early health check-up program for those in their 40s and 50s with a high prevalence of TNBC. For patients with breast cancer, in TNBC cases, except for poorly differentiated cases, neoadjuvant therapy must be applied first at all differentiation grades. The establishment of a policy system is necessary for the success of this process.

A Multiscale Spatiotemporal Epidemiological Analysis of Neighborhood Correlates of Triple-Negative Breast Cancer.

Women living in disadvantaged neighborhoods present with increased prevalence rates of triple-negative breast cancer (TNBC). This study takes a spatiotemporal epidemiological approach to understand the impact of socioenvironmental contextual factors on TNBC prevalence rates. We analyzed 935 TNBC cases from a major cancer center registry, between 2005 and 2017, to explore spatial and space-time clusters of TNBC prevalence rates at the census tract and neighborhood scales. Spatial regression analysis was performed to examine relationships between nine socioenvironmental factors and TNBC prevalence rates at both ecological scales. We observed spatial clustering of high TNBC prevalence rates along a north-south corridor of Miami-Dade County along Interstate 95, a region containing several majority non-Hispanic Black neighborhoods. Among the ecologic measures, the percent of a region designated as a brownfield was associated with TNBC prevalence rates at the tract-level (β = 4.27; SE = 1.08; P < 0.001) and neighborhood-level (β = 8.61; SE = 2.20; P < 0.001). Our spatiotemporal analysis identified robust patterns of hot spots of TNBC prevalence rates in a corridor of several disadvantaged neighborhoods in the northern half of the county. These patterns of TNBC align with the literature regarding at-risk groups and neighborhood-level effects on TNBC; however, remain to be validated in a population-based sample. Spatial epidemiological approaches can help public health officials and cancer care providers improve place-specific screening, patient care, and understanding of socioenvironmental factors that may shape breast cancer subtype through gene-environment and epigenetic interactions.

Immunohistochemistry-derived subtypes of breast cancer distribution in four regions of Ethiopia.

Different biological characteristics, therapeutic responses, and disease-specific outcomes are associated with different molecular subtypes of breast cancer (BC). Although there have been different studies on BC in the Ethiopian capital city of Addis Ababa, there have been few studies in other parts of the nation, and none have evaluated biological characteristics in other locations in the context of the extensive ethnic and genetic diversity found in Ethiopia. This study was carried out to evaluate the distribution of immunohistochemistry (IHC) subtypes of BCs throughout four Ethiopian regions. A total of 227 formalin-fixed paraffin-embedded (FFPE) tissue blocks were collected from tertiary hospitals in four Ethiopian regions between 2015 and 2021. The IHC staining was performed for subtyping, ER, PR, HER2, and Ki-67 proliferation markers. The mean age at diagnosis was 43.9 years. The percentage of ER and PR-negative tumors were 48.3% and 53.2%, respectively. The IHC subtypes showed the following distribution: 33.1% triple-negative breast cancer (TNBC), 27.6% luminal B, 25.2% luminal A, and 14.1% HER2 enriched. In multiple logistic regression analysis, grade III and HER2 positivity were associated with larger tumor size, and also originating from Jimma compared to Mekele. Patients with ER-negative, PR-negative, and TNBC were found in 48.3%, 53.2%, and 33.1% of cases, respectively, showing that half the patients could potentially benefit from endocrine treatment. A considerably high prevalence of TNBC was reported in our study, demanding additional research that includes genetic predisposition factors. Additionally, aggressive tumors were found in a high percentage of younger age groups, which must be considered when planning personalized treatment strategies.

Temporal Variation of Treatment Patterns and Survival Outcomes of Triple-Negative Breast Cancer Patients: A Real-World Experience From 2000 to 2014

BackgroundPrevious studies have reported a higher prevalence of triple-negative breast cancer (TNBC) in US Hispanic/Latina populations. However, survival outcomes and treatment approaches over time in Latin American females are scarcely reported. We aimed to evaluate the temporal variation in treatment patterns and overall survival (OS) outcomes of females with TNBC according to cancer stage. Materials and MethodsWe performed a single-center retrospective cohort study on 1840 females from 2000 to 2014. Patients were classified in 3 calendar periods (2000-2004, 2005-2009, and 2010-2014). The Kaplan-Meier method and multivariable regression analyses were employed. ResultsStage III cancer was identified in half of the population. Five-year OS estimates for cancer stages I, II, and IV remained unchanged across all calendar periods. However, we found worsening 5-year OS estimates in stage III females (49% in 2000-2004 and 31% in 2010-2014; P < .001). Despite increased uptake of overall use of neoadjuvant therapy in stage III females, the time from diagnosis to treatment initiation (P = .013) and time to complete the planned cycles (P < .001) increased over time. Fifty-sex percent of stage IV patients were untreated. Females aged ≥70 years were less likely to receive treatment. ConclusionsSurvival estimates were lower than those reported in high-income countries. Most females were diagnosed with advanced disease, and the OS for stage III females worsened over time. Our outcomes show difficulties in delivering timely neoadjuvant therapy in an overwhelmed healthcare system. Public health authorities should improve screening practices, develop regional clinical guidelines, and expand trial enrollment.

Antiproliferative Effect of Inorganic and Organic Selenium Compounds in Breast Cell Lines.

Triple-negative breast cancer (TNBC) is an aggressive, fast-growing tumor that is more likely to spread to distant organs. Among women diagnosed with breast cancer, the prevalence of TNBC is 20%, and treatment is currently limited to chemotherapy. Selenium (Se), an essential micronutrient, has been explored as an antiproliferative agent. Therefore, this study aimed to evaluate the effects of exposure to organic (selenomethionine, ebselen, and diphenyl diselenide) and inorganic (sodium selenate and sodium selenite) Se molecules in different breast cell lines. The compounds were tested at 1, 10, 50, and 100 μM for 48 h in the non-tumor breast cell line (MCF-10A) and TNBC derivatives cell lines (BT-549 and MDA-MB-231). The effects of Se on cell viability, apoptotic and necrotic processes, colony formation, and cell migration were analyzed. Exposure to selenomethionine and selenate did not alter the evaluated parameters. However, selenomethionine had the highest selectivity index (SI). The exposure to the highest doses of selenite, ebselen, and diphenyl diselenide resulted in antiproliferative and antimetastatic effects. Selenite had a high SI to the BT cell line; however, the SI of ebselen and diphenyl diselenide was low in both tumoral cell lines. In conclusion, the Se compounds had different effects on the breast cell lines, and additional tests are needed to reveal the antiproliferative effects of Se compounds.

High prevalance of triple negative markers in breast cancer patients in North Maharashtra

Breast cancer is the most prevalent cancer among women worldwide. The Bloom Richardson grading has been applied to most breast cancers. There are different biologic subtypes of breast cancer according to immunohistochemistry (IHC). Clinically, these subtypes are characterized on the basis of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Among them, Triple Negative Breast Cancer (TNBC) which lacks expression of the ER, PR, and HER-2-neu, is most aggressive form. TNBC cases have worse prognosis, require aggressive chemotherapy and are difficult to manage. The advent of neoadjuvant chemotherapy has highlighted the importance of IHC, Breast Ca and TNBC. The aim and objective of this study is to find prevalence of TNBC in Breast Cancer patients in North Maharashtra. This is a 3- Year ambiceptive analysis done to study the incidence of TNBC among Breast Cancer cases. Out of 58 Breast Cancer cases diagnosed in our institute, 30 cases in which IHC was done were included in this study. Postmortem breast cancer cases, core needle biopsies and mastectomies in which IHC was not done were excluded. Among 30 cases studied, 53.33% cases were TNBC, 23.33% cases were ER and PR positive, 10% cases were only HER-2-neu positive, 6.66% cases were only ER positive, 3.33% cases were only PR positive, and 3.33% cases were all three ER, PR and HER-2 neu positive. To conclude, India has considerably higher prevalence of TNBC, as compared to the Western countries. This finding has significant clinical relevance as it may have contributed to poor outcomes in patients with breast cancer in India. With advent of neoadjuvant chemotherapy, use of Modified Bloom- Richardson Grading &amp; IHC is of crucial importance. To understand the determinants of TNBC in India additional research is needed for diagnosis and treatment follow-up.

Abstract GS1-02: Racial disparity in tumor microenvironment and outcomes in residual breast cancer treated with neoadjuvant chemotherapy

Abstract Background: Black, compared to White women with localized breast cancer have higher mortality and worse distant recurrence free survival (DRFS). This has been attributed to social determinants of health and higher prevalence of triple negative breast cancer (TNBC) in Black compared to White women. Recent studies indicate that racial disparity in outcome is present in patients with estrogen receptor-positive (ER+), but not ER- disease, in particular in patients with residual disease after neoadjuvant chemotherapy (NAC). It has been shown that in some patients NAC may induce pro-metastatic changes in tumor microenvironment, such as increased density of tumor associated macrophages and portals for cancer cell dissemination to distant sites called TMEM doorways (TMEM score). TMEM score correlates with metastasis in patients with ER+/HER2- breast cancer. We hypothesized that racial disparity in DRFS in patients with residual ER+/HER2- disease is due to enhanced pro-metastatic components (macrophage and TMEM doorway density) in the tumor microenvironment post-chemotherapy in Black compared to White women. Methods: We performed a retrospective, multi-institutional study of TMEM score and macrophage density in the residual disease after NAC from 196 patients diagnosed with unilateral invasive ductal cancer of breast between 2004 and 2014. 99 patients self-identified as Black and 97 as White. TMEM doorways were visualized by triple immunohistochemistry for macrophages (CD68), tumor cells (panMena), and endothelial cells (CD31). The evaluation of TMEM score and macrophage density was done using automated image analysis. Tumor characteristics and patient survival were compared between Black and White patients. The relationship between TMEM score, macrophage density and DRFS was examined by log-rank test and multivariate Cox regression model. The covariates in Cox model included TMEM score, age (continuous), race (Black vs White), surgery type (mastectomy vs lumpectomy), tumor stage (T3 vs T1; T2 vs T1), lymph node status (positive vs negative), and tumor subtype (triple negative [TN] vs ER+/HER2-; other vs ER+/HER2-). Results: Black compared to White women were more likely to develop distant recurrence (49.5% vs 34%, p=0.04), receive mastectomy (69.7% vs 51.5%, p=0.014), and have higher grade (p=0.001). Tumors from Black patients had more macrophages and a higher TMEM score in the entire cohort (p=0.004; p=0.001 respectively) and in the ER+/HER2- subset (p=0.008; p=0.008 respectively), but not in the TNBC subset. High TMEM score was associated with worse DRFS in all patients (p=0.004) and in the ER+/HER2- (p=0.03), but not in TNBC. In multivariate Cox model, TMEM score was an independent prognostic factor in the entire cohort (HR, 1.92; 95%CI, 1.15-3.22; p=0.01) and trended towards significance in ER+/HER2- disease (HR, 2.13; 95%CI, 0.96-4.71; p=0.06). TN, compared to ER+/HER2- cancers had higher TMEM score (p=0.01), and macrophage density (p=0.001). Conclusion: Racial disparity in outcome in patients with localized breast cancer may be due to a more pronounced pro-metastatic response to chemotherapy in Black, compared to White patients with ER+/HER2- disease. Thus, higher prevalence of TNBC in Black patients may not be the controlling factor in racial disparity. Citation Format: Burcu Karadal, Gina Kim, Ved Sharma, Jessica Pastoriza, Isabelle Oktay, Yu Lin, Xianjun Ye, Jiyue Qin, Esther Cheng, Nurfiza Ladak, John Condeelis, Esther Adler, Paula Ginter, Timothy D’Alfonso, Xiaonan Xue, David Enterberg, Joseph Sparano, Maja Oktay. Racial disparity in tumor microenvironment and outcomes in residual breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-02.

Neighborhood and racial influences on triple negative breast cancer: evidence from Northeast Ohio.

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher recurrence rates and poorer prognoses and most prevalent among non-Hispanic Black women. Studies of multiple health conditions and care processes suggest that neighborhood socioeconomic position is a key driver of health disparities. We examined roles of patients' neighborhood-level characteristics and race on prevalence, stage at diagnosis, and mortality among patients diagnosed with BC at a large safety-net healthcare system in Northeast Ohio. We used tumor registry to identify BC cases from 2007 to 2020 and electronic health records and American Community Survey for individual- and area-level factors. We performed multivariable regression analyses to estimate associations between neighborhood-level characteristics, measured by the Area Deprivation Index (ADI), race and comparative TNBC prevalence, stage at diagnosis, and total mortality. TNBC was more common among non-Hispanic Black (53.7%) vs. non-Hispanic white patients (46.4%). Race and ADI were individually significant predictors of TNBC prevalence, stage at diagnosis, and total mortality. Race remained significantly associated with TNBC subtype, adjusting for covariates. Accounting for TNBC status, a more disadvantaged neighborhood was significantly associated with a worse stage at diagnosis and higher death rates. Our findings suggest that both neighborhood socioeconomic position and race are strongly associated with TNBC vs. other BC subtypes. The burden of TNBC appears to be highest among Black women in the most socioeconomically disadvantaged neighborhoods. Our study suggests a complex interplay of social conditions and biological disease characteristics contributing to racial disparities in BC outcomes.

Comparison of clinicopathological characteristics, disease free survival and recurrence in triple negative breast cancer(TNBC) with Non-TNBC

Introduction: TNBC is associated with high mortality, morbidity and low survival rates. This study is aimed to study difference in pathological characteristics, disease free survival and recurrence between TNBC and Non-TNBC. Materials and Methods: Total 208 patients, who are diagnosed cases of breast carcinoma visiting our out patient department between August 2020 and July 2022 were enrolled. Demographic details, details during the presentation, pathological characterstics including the HPE, grade and receptor status, modality of treatment were taken. Enrolled patients were followed up. At the end of the study period, 2 year disease free survival, overall survival, recurrence of malignancy were noted. 102 patients who lost followup, status unknown or who has not completed a period of 2 years after diagnosis of Breast carcinoma were excluded. 106 patients were nalised, details were entered in excel sheet. Patients were divided into TNBC and Non-TNBC group and compared. Results: Prevalence of TNBC in our study was 22.6. Tumor size is more at presentation in TNBC compared to Non TNBC. All patients with TNBC had positive nodes during presentation (100%Vs78%). Presence of metastasis at the time of diagnosis is more in TNBC group(20.8%Vs 8.5%). Both groups has Intraductal Carcinoma as the predominant variant. Most of the TNBC had poorly differentiated grade tumors when compared to Non-TNBC. TNBC has more local(38.8% Vs 18.7%) and metastatic(22.22% Vs 4%) recurrences. 2 year Diseases free survival was more in Non-TNBC group(77.33% Vs 38.88%). Conclusions: TNBC has overall lesser disease survival period, more local and metastatic recurrences. Stage at diagnosis in TNBC is more advanced. Hence TNBC has got poor prognosis and high mortality. Early diagnosis and treatment is the key in reducing the mortality and better prognosis.

Association of Community Cancer Centers: Institution-Directed Quality Improvement of Genetic Counseling and Testing for Community Oncology Patients with Breast Cancer

Hereditary breast cancer accounts for 10 percent of all breast cancers currently diagnosed in the United States. 1 About 30 percent of the known inherited breast cancers are associated with pathogenic (or likely pathogenic variants) in BRCA1/2, 2,3 the most understood germline mutations. These cancers occur earlier in life and more often in patients with cancer susceptibility genes. The mean age of patients with germline BRCA1/2 pathogenic variants who develop breast cancer is considerably lower, compared to the mean age of patients with sporadic breast cancer (42 years vs. 64 years, respectively), which clearly factors into decision making. There is a higher prevalence of triple-negative breast cancer (estrogen receptor [ER]−, progesterone receptor [PR]−, human epidermal growth factor receptor 2 [HER2]-) among those with a pathogenic BRCA1 variant, while individuals with a pathogenic variant in BRCA2 more commonly develop ER+ breast cancer and lower grade tumors. 4 Additionally, patients with a pathogenic variant in BRCA1/2 have a higher risk of developing a second primary breast cancer and other cancers, including pancreatic cancer, ovarian cancer in women, and prostate cancer in men. 3,4

Abstract LB561: Germline mutational profiling of TNBCs in an Indian cohort

Abstract Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. The high TNBC prevalence (&amp;gt;25%) in India as compared to the western population (10-15%) remains to be a challenge in clinical management. The association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. However, these studies are predominantly from germline profiling of TNBCs representative of western population. Therefore, we aimed to investigate the germline profiles of breast cancer patients in India using a multi-institutional TNBC cohort based on ACMG consensus multi-gene NGS panel. Of 193 TNBC patients, we identified 57 pathogenic mutations (diagnostic yield = 29.53%) from various genes of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. We observed a high prevalence of BRCA1 mutations (41/193, 21.24%) and BRCA2 mutations (8/193, 4.14%) in our cohort as compared to published literature. Additionally, 8 pathogenic mutations were also reported in non-BRCA cancer pre-disposing genes associated with the HR pathway like ATM, CHEK2, PALB2. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. The most common type of mutations was found to be frame-shift which may cause protein truncation and loss of function. Furthermore, we identified 48 variants of unknown significance (24.9%) of which about 7% were in the BRCA1/2 genes. Data mining from global databases like TCGA, Genome Asia indicated that the novel mutations were unique to the Indian population compared to the germline profiles of different ethnicities. Our study confirms the major contribution of BRCA1/2 genes in TNBCs as reported in the literature. A high percentage of the women were found to be associated with young age onset which may be attributed to BRCA mutations. We have also assessed the association of clinicopathological parameters such as tumor grade, stage, recurrence to the germline mutational status. Our analysis shows significant association of germline mutational status with family history thus underlin the importance of multi-gene panel testing as recommended by NCCN guidelines. Moreover, our results also emphasize the need for designing/implementing guidelines specific to Indian population. In summary our results indicate that Indian TNBCs have a high prevalence of BRCA1/2 mutations. Large scale studies in future are warranted to validate these preliminary findings. Citation Format: Chaitanyanand Koppiker, Ashwini Bapat, Siddharth Gahlaut, Naveen Luke, Jisha John, Rupa Mishra, Aishwarya Konnur, Namrata Namewar, Ruhi Reddy, Shaheen Shaikh, Rituja Banale, Smeeta Nare, Laleh Busheri, Asha Reddy, Ashraf Mannan, Sabarinathan Radhakrishnan, Selvi Radhakrishna, Santosh Dixit. Germline mutational profiling of TNBCs in an Indian cohort [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 LB561.

Triple-negative breast cancer prevalence in Africa: a systematic review and meta-analysis.

ObjectiveThe aggressive triple-negative breast cancer (TNBC) subtype disproportionately affects women of African ancestry across the diaspora, but its frequency across Africa has not been widely studied. This study seeks to estimate the frequency of TNBC among African populations.DesignSystematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.Data sourcesPubMed, EMBASE, African Journals Online and Web of Science were searched on 25 April 2021.Eligibility criteria for selecting studiesWe included studies that use breast cancer tissue samples from indigenous African women with sample size of eligible participants ≥40 and full receptor status for all three receptors (oestrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2)) reported.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias using the modified assessment tool by Hoy et al. (2012) for prevalence studies. A random-effects meta-analysis was performed, and data were pooled using the inverse-variance method and logit transformation. Pooled frequencies were reported with 95% CIs calculated with the Clopper-Pearson method and heterogeneity quantified with I2 statistic. GRADE assessed the certainty of the evidence.Results1808 potentially eligible studies were identified of which 67 were included in the systematic review and 60 were included in the meta- analysis. Pooled TNBC frequency across African countries represented was estimated to be 27.0%; 95% CI: 24.0% to 30.2%, I2=94%. Pooled TNBC frequency was highest across West Africa, 45.7% (n=15, 95% CI: 38.8% to 52.8%, I2=91%) and lowest in Central Africa, 14.9% (n=1, 95% CI: 8.9 % to 24.1%). Estimates for TNBC were higher for studies that used Allred guidelines for ER/PR status compared with American Society of Clinical Oncology(ASCO)/College of American Pathologists(CAP) guidelines, and for studies that used older versions of ASCO/CAP guidelines for assessing HER2 status. Certainty of evidence was assessed to be very low using GRADE approach.ConclusionTNBC frequency was variable with the highest frequency reported in West Africa. Greater emphasis should be placed on establishing protocols for assessing receptor status due to the variability among studies.

Abstract P3-07-08: Germline mutational profiling in Indian TNBCs

Abstract Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. The high TNBC prevalence (&amp;gt;25%) in India as compared to the western population (10-15%) remains to be a challenge in clinical management. The association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. However, these studies are predominantly from germline profiling of TNBCs representative of western population. Therefore, we aimed to investigate the germline profiles of Indian breast cancer patients using a multi-institutional TNBC cohort based on ACMG consensus multi-gene NGS panel. In our study cohort of 193 TNBC patients, we identified 57 pathogenic mutations (diagnostic yield = 29.53%) from various genes of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. We observed a high prevalence of BRCA1 mutations (41/193, 21.24%) and BRCA2 mutations (8/193, 4.14%) in our cohort as compared to published literature. Additionally, 8 pathogenic mutations were also reported in non-BRCA cancer pre-disposing genes associated with the HR pathway like ATM, CHEK2, PALB2. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. The most common type of mutations was found to be frame-shift which may cause protein truncation and loss of function. Furthermore, we identified 48 variants of unknown significance (24.9%) of which about 7% were in the BRCA1/2 genes. Data mining from global databases like TCGA, Genome Asia indicated that the novel mutations were unique to the Indian population compared to the germline profiles of different ethnicities. Our study confirms the major contribution of BRCA1/2 genes in TNBCs as reported in the literature. A high percentage of the women were found to be associated with young age onset which may be attributed to BRCA mutations. Further analysis to investigate the association of tumor size, tumor grade, survival analysis with mutational profiles is in process. Similarly, we are also assessing. family history to underline the importance of multi-gene panel testing as recommended by NCCN guidelines. Moreover, our results also emphasize the need for designing/implementing guidelines specific to Indian population. In summary our results indicate that Indian TNBCs have a high prevalence of BRCA1/2 mutations. Large scale studies in future are warranted to validate these preliminary findings. Citation Format: C B Koppiker. Germline mutational profiling in Indian TNBCs [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-07-08.

Triple Negative Breast Cancer Prevalence in Indian Patients over a Decade: A Systematic Review

Triple Negative Breast Cancer (TNBC) is an aggressive variant of breast cancer with penurious prognosis and limited therapeutic options. This subtype is characterised with higher incidence rate among the younger women, aggressive tumour behaviour, with early local recurrence and distant metastasis leading to poor outcomes.

Abstract PO-092: Racial survivial disparities in triple negative metastatic breast cancer (MBC)

Abstract Breast cancer racial survival disparity is often explained through late-stage presentation and the high prevalence of triple-negative breast cancer (TNMBC) and poor dose intensity of treatment among Black women. This study attempted to equalize disease factors through analysis of only women with triple-negative breast cancer and evaluating the course of care only through the TNMBC course. The racial differences of neighborhood deprivation index (NDI) and baseline depression, and anxiety symptoms at the diagnosis of TNMBC were examined. The aims of the study were to 1. Compare the time to first TNMBC disease progression and overall survival of women with TNMBC and compare by race. 2. Document NDI, baseline anxiety and depression at the diagnosis of TNMBC and compare by race. Methods: Retrospective review of patients deceased from TNMBC between November 1, 2016, through December 2019 at a National Cancer Institute-designated medical oncology breast cancer clinic. Overall survival (OS) and time to first disease progression (TTFP) calculated in days from metastatic diagnosis, anxiety and depression scores obtained through the Generalized Anxiety and Depression scores (GAD-7) and the Patient Health Questionnaire (PHQ-9) measuring depression. Both from self-report at the first TNMBC visit, higher scores indicating higher symptoms. NDI obtained from zip code (higher scores = more deprivation). Dose intensity of first treatment (DIFT) - percentage drugs received/prescribed. Analysis of variance, descriptive statistics, and independent t-tests used for comparative analysis; Hedge's g was calculated for effect sizes due to uneven sample sizes. Results: There were n=54 total patients, n=45- White, n=9 Black. Age - Black, 55.3 (SD 13.0), White 56.3(SD 12.9). NDI -Black 74.9 (SD 19.3), White 55.6 (SD 19.5), p=.009, Hedge's g =0.99. DIFT - Black .88%, White, .84% (p=.523). PFS first treat- Black, 13.8(SD 8), White 20.8 (SD29.6), p= .183, Hedge's g =0.26. Overall TNMBC survival -Black 26.1 months (SD 13.5), White 46.7 months (SD 53.6),p=.032, Hedge's g = 0.414. GAD - Black,9.3 (SD-9.5), White -6.14 (5.8), p=.307, Hedge's g - .48. PHQ - Black 5.7 (SD 7.0), White 4.2 (SD 5.1), and p=.59, Hedge's g= 0.25. Discussion: Despite equalizing the stage and subtype of MBC, there is a wide racial survival disparity that is not explained by the dose intensity of the first treatment. A possible explanatory pathway is that neighborhood deprivation, more severe among Black patients, may be causing high anxiety and mild depression, leading to worse overall TNMBC survival. These data provide the impetus to pursue stress from neighborhood deprivation as an etiology for TNMBC racial survival disparity. Obtaining measurement and markers of stress and depression over the TNMBC illness trajectory, better characterizing neighborhoods for multiple aspects of deprivation and seeking strategies to improve the support that neighborhoods can offer women with TNMBC may help to identify targets for mitigation of factors leading to poor TNMBC survival outcomes. Citation Format: Margaret Q. Rosenzweig, Bethany Nugent, Meaghan McQuire, Jian Q. Xhao. Racial survivial disparities in triple negative metastatic breast cancer (MBC) [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-092.