Rates Of Triple-negative Breast Cancer Research Articles

Abstract PO3-13-12: ER-positive/HER2-negative breast cancer in Adolescent & Young Adult (AYA) age group has a specific biological feature and worse outcome compared to other generations

Abstract Background: Adolescents & Young Adults (AYA) is commonly defined as patients younger than 40 years old. Breast cancer patients in AYA has been reported to have poor outcome compared to other generation, however, the clinicopathological and biological features of AYA breast cancer remains controversial partly because many previous studies did not consider the difference in subtypes by age. We aim to clarify the features of AYA compared with the other age group in ER-positive/HER2-negative breast cancer, assuming the effects of age-related hormonal status. Material and Methods: Each analyzed cohort were divided into four age groups; AYA (15-39yo), perimenopausal (40-55yo), menopausal (55-65yo), and old (65+yo). Clinicopathological and biological features were analyzed using gene set variation analysis and the xCell algorithm using mRNA expression profiles of large independent public databases (METABRIC; n = 1,903, GSE96058; n = 3,273). Results: We found that both clinical and pathological T-category of AJCC staging were larger in AYA and Old compared from the other groups. Pathological N-category as well as pathological Stage were higher in AYA. Nottingham histological grade 3 was significantly higher in the AYA compared with the other older groups. Among the subtypes, AYA breast cancer was significantly associated with higher rate of triple-negative breast cancer compared to the others, as expected. Considering the whole cohort, ER and PgR positivity trended to be lower, but HER2-positivity trended to be higher in AYA. Within the ER-positive/HER2-negative subtype, PgR positivity was higher in the AYA and Perimenopausal groups compared to others. AYA had poorer disease-specific survival than other groups (p = 0.010 and p = 0.002, respectively), as well as overall survival, especially compared to perimenopausal group. The survival difference was more pronounced in ER-positive/HER2-negative breast cancer patients. In biological analysis in ER-positive/HER2-negative subtype, we found that estrogen response late signaling level decreased as the age group gets older. AYA breast cancer had significant enrichment in cell proliferation-related gene sets (G2M checkpoint, E2F targets, and MYC target v1), other pro-cancerous gene sets (MTORC1, unfolded protein response, and PI3K/ACT/MTOR signaling), consistently in two cohorts (all p ≦ 0.028), when compared to the other age groups. Interestingly, the features were observed even in the small tumor size (T1/T2) subgroup. Furthermore, AYA breast cancer showed significantly high BRCAness (all p≦0.002) and DNA repair (all p≦0.023) compared to other age groups. The infiltration fraction of several immune cells: CD8+ T cells, M1 macrophages, regulatory T cells, helper type 2 T cells, were significantly higher, and M2 macrophages were significantly lower in AYA, consistently in two cohorts. Conclusion: ER-positive/HER2-negative breast cancer in AYA was highly proliferative with high immune cell infiltrations compared to other generations. This may be related to the difference in outcomes in each age group. Considering these unique features may enable us to fine tune treatment strategies for AYA. Citation Format: Masanori Oshi, Akimitsu Yamada, Mahato Sasamoto, Kei Kawashima, Yoshie Fujiwara, Shoko Adachi, Shinya Yamamoto, Kazutaka Narui, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe. ER-positive/HER2-negative breast cancer in Adolescent & Young Adult (AYA) age group has a specific biological feature and worse outcome compared to other generations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-12.

Abstract 1014: Disparities of triple negative breast cancer in Mississippi

Abstract Background: Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers nationwide with disparities of incidence and outcomes among races, geographic locations, and other factors. This study is aimed to analyze the differences in the rate of TNBC, patient conditions at time of diagnosis, and death from TNBC among women in Mississippi. Methods: A retrospective study was conducted to serially review breast cancer cases diagnosed in the University of Mississippi Medical Center during May 2016 to May 2023. The entire breast cancer population was then stratified by race. The rate of TNBC, age and BMI at time of diagnosis, the rate of expiration were compared between African American (AA) and Caucasian American (CA) women with breast cancer. Two-tailed Student’s T-test was used to calculate the difference in mean values, and Chi-Square Test was used to compare the difference in rates or percentages. The significant p value was set at p<0.05. Results: In total 291 women with breast cancer, AA patients were 195 (67.01%), CA patients were 88 (30.24%), and other were 8 (2.75%). The mean age of all patients was 58.3 years-old (ranged 24-97). The mean BMI was 31.19. The patients with TNBC were 109 (37.46%) in entire studied population. A total of 32 (1.6%) patients, including 14 TNBC and 18 non-TNBC were expired with an average age of 61.84 and an average survival time of 20 months from diagnosis to expiration. As compared to CA patient population, AA breast cancer patients had onset at younger age (58.08±0.88 vs. 59.18±1.36), had a higher BMI (31.79±0.62 vs. 28.25±1.05, p=0.017), higher percentage of TNBC (41.54% vs. 30.68%, p=0.082 and OR=1.605), and higher rate of expiration (11.28% vs, 9.1%). Also, as compared to CA expired patients with breast cancer, AA expired patients had higher BMI (29.57 vs. 28.61), shorter survival time (17.5 months vs. 19.4 months), and died at younger age (61.84-year old vs. 66.38-year old) with a higher proportion of TNBC subtype (54.6% vs 12.5%, p=0.045, OR=9.6). Conclusions: Breast cancer is greatly disparate racially between AA and CA and geographically between Mississippi and US national average. The disparities are manifested in the proportion of TNBC subtype, age at onset of breast cancer, BMI at time of diagnosis, and death rate. Citation Format: Navdeep Kaur, Javaria A. Khan, Jinghe Mao, Diva Melvin, Muhammad M. Hassan, Xinchun Zho. Disparities of triple negative breast cancer in Mississippi [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 1014.

Metal-Organic Framework-Based Nano-Activators Facilitating Microwave Combined Therapy via a Divide-and-Conquer Tactic for Triple-Negative Breast Cancer.

Aiming at the clinical problems of high recurrence and metastasis rate of triple-negative breast cancer, a divide-and-conquer tactic is developed. The designed nanoactivators enhance microwave thermo-dynamic-chemotherapy to efficiently kill primary tumors, simultaneously ameliorate the immunosuppressive microenvironment, activate the tumor infiltration of T lymphocytes, and enhance the accumulation and penetration of PD-1/PD-L1 immune agents, ultimately boosting the efficacy of immune checkpoint blocking therapy to achieve efficient inhibition of distal tumors and metastases. Metal-organic framework (MOF)-based MPPT nano-activator is synthesized by packaging chemotherapeutic drug Pyrotinib and immunosuppressant PD-1/PD-L1 inhibitor 2 into MnCa-MOF and then coupling target molecule triphenylphosphine, which significantly improved the accumulation and penetration of Pyrotinib and immunosuppressant in tumors. In addition to the combined treatment of microwave thermo-dynamic-chemotherapy under microwave irradiation, Mn2+ in the nano-activator comprehensively promotes the cGAS-STING pathway to activate innate immunity, microwave therapy, and hypoxia relief are combined to ameliorate the tumor immunosuppressive microenvironment. The released Pyrotinib down-regulates epidermal growth factor receptor and its downstream pathways PI3K/AKT/mTOR and MAPK/ERK signaling pathways to maximize the therapeutic effect of immune checkpoint blocking, which helps to enhance the antitumor efficacy and promote long-term memory immunity. This nano-activator offers a generally promising paradigm for existing clinical triple-negative breast cancer treatment through a divide-and-conquer strategy.

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 HER2-11: HER2-11 Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB)

Abstract Title: Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB) Background: Characterization of HER2 status has focused on HER2 overexpressing BC, which are uniquely sensitive to HER2-directed therapy. However, approximately 60% of BC traditionally characterized as HER2-negative express low levels of HER2 on immunohistochemistry (IHC). Although these ‘HER2-low’ cancers are insensitive to traditional HER2 blockade, a recent randomized clinical trial showed that antibody drug conjugates such as trastuzumab deruxtecan (T-DXd) are effective in this population. Given the heterogenity of low level HER2 expression and the impact of T-DXd on outcomes in this population, further data on the epidemiology and prognosis of HER2-low BC is needed. Methods: We conducted a retrospective cohort study of patients (pts) in the NCDB diagnosed from 2010 to 2019 with invasive BC classified as HER2-negative, and with HER2 IHC results available. We compared demographics and other clinical characteristics of HER2 0 vs HER2-low (defined as IHC score of 1+ or 2+) cases in this cohort. A logistic regression was used to quantify the independent association of demographic and clinical factors with HER2-low status, and odds ratios (OR) and 95% confidence intervals (CI) were reported. Overall survival (OS) was compared for HER2 0 vs HER2-low by receptor subtype and stage, and a multivariable Cox model was fit to also control for age, race/ethnicity, comorbidity score, treatment facility type, grade, and histologic type. In pts who received neoadjuvant chemotherapy (NAC), a logistic regression was used to determine if pathological complete response (pCR) rate was different between HER2-low and HER2 0 pts. Results: We identified 1,191,389 pts, including 394,937 HER2 0 and 796,452 HER2-low; median follow-up was 54 months with 84.1% of pts surviving. Hispanic and Black pts and pts with higher grade, non-ductal, triple-negative breast cancer (TNBC) and affect minority Hispanic and Black women (table 1). On multivariable analysis, TNBC (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.47 – 0.49), lobular (OR 0.74, 95% CI 0.73 – 0.75) and other non-ductal histology (OR 0.66, 95% CI 0.64 – 0.67) had lower likelihood of HER2-low status. Hispanic ethnicity remained associated with lower likelihood of HER2-low (OR 0.89, 95% CI 0.87 – 0.91), whereas Black race was associated with a slight increased likelihood of HER2-low status (OR 1.06, 95% CI 1.04 – 1.08). In multivariable survival analysis of TNBC patients, HER2-low BC was associated with improved OS for stage 2 (hazard ratio [HR] 0.93, 95% CI 0.90 – 0.96), stage 3 (HR 0.92, 95% CI 0.88 – 0.96) and stage 4 (HR 0.92, 95% CI 0.87 – 0.97) cancer. By contrast, survival analysis of hormone receptor positive cancer showed that HER2-low BC was associated with improved OS only for stage 4 disease (HR 0.96, 95% CI 0.92 – 0.99). In 62,667 pts receiving NAC, HER2-low status was associated with a lower likelihood of pCR (OR 0.88, 95% CI 0.84 – 0.92). Conclusions: HER2-low BC is most frequently HR+ with a ductal histology, and is associated with a lower likelihood of response to chemotherapy but an improved OS, especially for metastatic cases. This lower pCR in the HER2-low population could be explained by a higher proportion of these tumors being HR+. There are racial/ethnic differences in the incidence of HER2-low BC, largely mediated by differences in rates of TNBC, and fewer Black and Hispanic pts will be candidates for therapies targeting low level HER2 expression. Citation Format: Daniel Peiffer, Frederick M. Howard, Nan Chen, Olwen M. Hahn, Rita Nanda, Olufunmilayo I. Olopade, Dezheng Huo. HER2-11 Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB) [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 HER2-11.

Abstract P6-04-11: Improved quantitative fibrosis indices reveal diverse survivals of triple negative breast cancer patients

Abstract Background: The ability of cancer cells to metastasise influences the mortality rate of patients with cancer. Extracellular matrix (ECM) from stromal organization is associated with tumorigenesis and metastasis in breast cancer. It is proposed that morphological features of collagen, based on second harmonic generation (SHG) microscopy, within the tumour environment can be a quantitative image-based biomarker for to predict the survival rate of triple-negative breast cancer (TNBC) patients. To this, we have developed quantitative fibrosis indices by combining multiple collagen features in breast tumour to reveal the diverse survivals of TNBC patients. Method: The patients (n = 216) in this study were diagnosed with TNBC in Singapore from 2003 to 2015. Disease-free survival (DFS) and overall survival (OS) were defined as time from the point of diagnosis to recurrence or to death/the date of the last follow-up, respectively. The constructed tissue microarrays (TMA) of breast tumours were scanned by the SHG microscope (Genesis, HistoIndex Pte. Ltd., Singapore). 33 collagen parameters were quantified from each sample. These collagen parameters were used to build disease free survival (DFS) index, overall survival (OS) index for prediction of early recurrence (DFS< 1 year) and early death (OS< 4 years), respectively. Kaplan-Meier survival analysis was further performed to assess long-term survival of TNBC patients with high and low risk as stratified by the indices, tumour grade and tumour size. The indices were validated using leave-one-out method. Results: Both DFS-index and OS-index were created using 10 collagen parameters chosen by sequential selection methods. Due to insufficient follow-up time, 12 patients and 81 patients were excluded from the early recurrence analysis and early death analysis, respectively. The DFS-index could differentiate low-risk patients with DFS≥1 year (n=179) and high-risk patients with DFS< 1 year(n=25) (training p< 0.001; validation p=0.157) with a cut-off value DFS-index=0.880. The OS-index could differentiate the low-risk patients with OS≥4 years (n=101) and high-risk patients with OS< 4 years (n=34) (training p< 0.001; validation p=0.011) with a cut-off value OS-index=0.703. The log-rank test showed DFS-index (training p = 0.001; validation p=0.025) and OS-index (training p < 0.001; validation p=0.011) could be used for the prediction of disease-free survival and overall survival. Kaplan-Meier survival analysis revealed tumour size>20mm (DFS, p=0.605; OS, p=0.136) and tumour grade=3 (DFS, p=0.328; OS, p=0.768) had poor predictive value in this study. Conclusion: Quantitative assessment of fibrosis in breast cancer correlates with long-term survival of TNBC patients. This study used DFS-index and OS-index combined complex morphological collagen features and obtained better prediction results than tumour size and tumour grade. Table. The difference between low and high risk groups differentiated by developed indices, tumour size and tumour grade. Low-risk group has a longer DFS and OS months based on DFS-index and OS-index. Citation Format: Yayun Ren, Dean Tai, Ying Zhao, Puay Hoon Tan. Improved quantitative fibrosis indices reveal diverse survivals of triple negative breast cancer patients [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 P6-04-11.

Abstract C064: IGF-II regulates a critical mitochondrial protein, Magmas, with differential expression between African American and Non-Hispanic White women with TNBC

Abstract Breast cancer is the most common malignancy in women. Young African American (AA) women are affected by a higher incidence and mortality rate of triple-negative breast cancer (TNBC) compared to Non-Hispanic White (NHW) women. Currently, available treatment options are suboptimal, with a 5-year survival of less than 12% for metastatic TNBC. Our laboratory demonstrated that IGF-2 plays a pivotal role in the tumor aggressiveness of AA women. Moreover, tissues from AA women express high levels of IGF-2 and exhibit high activation of IGF-2 signaling pathways associated with tumorgenesis and chemoresistance. An emerging pathway linked to IGF-2 mediated chemoresistance and cell survival in TNBC is the regulation of mitochondrial and survival proteins. Mitochondrial Magmas is a mitochondrial protein found in all eukaryotic cells that is required for cell viability. It functions to transport nuclear proteins from the inner mitochondrial membrane to the mitochondrial matrix. Magmas can buffer increased reactive oxidative species (ROS) and promote survival of cancer cells. Overexpression of Magmas reduced ROS and enhanced cellular tolerance to oxidative stress; however, its downregulation raised cellular ROS and made cells more vulnerable to ROS-mediated death. Given the role of IGF-2 in regulating mitochondrial proteins, we investigated if IGF-2 regulated Magmas. We hypothesize that IGF-2 increases Magmas, and since AA women express higher levels of IGF-2, they will express higher Magmas levels. We used the CRL-2335 AA TNBC cell line and an IGF-2 knockdown of those same cells. Western blotting was used to detect the specific isoforms of IGF-2 and Magmas from cell lysates. Immunohistochemistry (IHC) characterized Magmas expression in paired, normal-tumor breast cancer tissues. Real time PCR was used to evaluate the expression of IGF2 and MAGMAS. The preliminary results showed that IGF-2 knockdown in CRL-2335 AA TNBC cells significantly decreased Magmas protein expression and its corresponding mRNA. In addition, tissue analysis demonstrated high levels of Magmas staining in TNBC tissue while little or no staining was detected in the normal tissues. Furthermore, tumor tissues of AA women showed significantly higher expression of Magmas as compared to tissues from NHW women. Targeting Magmas represents a novel and much needed tool to treat TNBC. Our team is currently validating Magmas as a target for Theranostics treatment, a promising emerging radiotherapy for TNBC patients. Citation Format: Jennifer D. Tran, Alfonso D. Duran, Qian-Wei Tan, Frankis G. Almaguel, Daisy De León. IGF-II regulates a critical mitochondrial protein, Magmas, with differential expression between African American and Non-Hispanic White women with TNBC [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C064.

Abstract A011: Whole genome sequencing of the Alabama Hereditary Cancer Cohort to identify African American breast cancer genetic risk variants

Abstract Regardless of having higher rates of triple-negative breast cancer (TNBC) and breast cancer-related deaths, African Americans are drastically understudied in hereditary breast cancer research. Our group has established the Alabama Hereditary Cancer Cohort to carry out next-generation sequencing (NGS) to address this gap. These efforts aim to identify inherited breast cancer risk variants in African Americans. Interestingly, African American TNBC tumors have been investigated through NGS, identifying somatic mutations unique to African American breast cancer. Now, African American-specific variants associated with inherited risk need to be identified, including those in genes harboring somatic mutations in African American TNBC. This study carried out whole genome sequencing (WGS) to investigate inherited African American breast cancer risk. All coding and non-coding regions of the nuclear genome and the entirety of the mitochondrial genome were explored, all of which can play a role in hereditary breast cancer risk. Individuals provided a blood or saliva sample for DNA extraction upon study consent. Subsequently, paired-end Illumina sequencing was carried out. Fastq files were trimmed using Trimmomatic and further processed according to the Genome Analysis ToolKit Best Practices, resulting in variant call format (VCF) files. Coding, non-coding, and mitochondrial regions were individually extracted using VCFtools and UCSC Table Browser tracks. Coding and mitochondrial variants were annotated using Annovar and MSeqDR, respectively. Coding variants were further filtered for minor allele frequency (MAF) classes (i.e., rare and low-frequency) and mutation type (i.e., protein-truncating variants; PTVs) using R (v. 4.2). Preliminary WGS data of 60 African American hereditary breast cancer cases have identified statistically significant rare and low-frequency PTVs in genes reported to harbor somatic mutations exclusively in African American TNBC tumors. Furthermore, we have identified variants in prostate cancer susceptibility genes that are statistically associated with African American breast cancer risk. We have also identified multiple variants in the mitochondrial genome that are statistically linked to breast cancer risk, some African American-specific. Our data shows that WGS is an invaluable tool for identifying breast cancer susceptibility variants. Further sequencing and functional analyses will validate our preliminary findings. Citation Format: Troy LoBue, Isaac Mcneely, Nancy Merner. Whole genome sequencing of the Alabama Hereditary Cancer Cohort to identify African American breast cancer genetic risk variants [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A011.

Characteristics and chronologically changing patterns of late-onset breast cancer in Korean women of age ≥ 70 years: A hospital based-registry study

BackgroundWomen from Asian and western countries have vastly different ages of onset of breast cancer, with the disease tending to occur at an older age in the West. Through an investigation of the patterns of old-onset breast cancer (OBC) in Korean women, we aimed to identify the characteristics of Korean OBC and evaluate whether these patterns are changing in relation to increasing westernization.MethodsThis study retrospectively evaluated 102,379 patients who underwent surgical treatment of primary breast cancer between January 1, 2000 and December 31, 2013 in Korea. We used hospital -based breast cancer registry and analyzed data from these patients using multiple linear regression analysis to compare the characteristics and chronologically changing patterns between OBC (70 years of age or older) and non-OBC (40–69 years of age) patients in Korea.ResultsA total of 6% of the 102,379 patients had OBC. Overall, OBC had more favorable biological features, such as a higher incidence of luminal A subtype, than did non-OBC, except for a higher incidence rate of triple-negative breast cancer (TNBC). However, OBC also presented with a higher overall disease stage, including higher T and M stages. Although the incidence rates of both OBC and non-OBC have increased overtime, the relative proportion of OBC patients has slightly increased, whereas that of non-OBC has slightly decreased. The increase in the incidence of both OBC and non-OBC was primarily due to the luminal A subtype.ConclusionsBased on a hospital-based registry, overall, Korean OBC had favorable biological features but showed a higher rate of TNBC and advanced cancer stages. The incidence trend of breast cancer in Korea is slowly shifting toward an older age at onset, largely due to the luminal A subtype. Our results may provide novel insights into OBC in Asia, and aid in the development of optimal management of the disease in Asia.Trial registrationRetrospectively registered.

Clinical Observation of Zhengyuan Capsule Combined with Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer.

Objective To study the clinical effect of Zhengyuan capsule combined with neoadjuvant chemotherapy in the treatment of triple-negative breast cancer (TNBC). Methods From September 2014 to September 2017, 120 TNBC patients who underwent radical mastectomy in our hospital were randomly divided into control group (n = 60) and observation group (n = 60). The short-term curative effect, the incidence of toxicity and side effects, and the score of quality of life of the patients were compared. Both recurrence and metastasis rates were also analyzed. Results The combined treatment of Zhengyuan capsule with neoadjuvant chemotherapy significantly improved the objective remission rate (70.00% in the observation group versus 40.00% in the control group) (P < 0.05). Moreover, this combined treatment significantly decreased the total incidence of side effects (35.00% versus 75.00%). Accordingly, the score of quality of life was also increased in patients treated with Zhengyuan capsule plus neoadjuvant chemotherapy (P < 0.05). Furthermore, supplementation of Zhengyuan capsule can significantly suppress both the recurrence and metastasis rate of TNBC in patients treated with neoadjuvant chemotherapy after radical mastectomy in following 3 years (30.00% versus 10.00%, P < 0.05). Conclusion Zhengyuan capsule effectively improves the short-term curative effect, reduces the side effects of chemotherapy, and improves the quality of life of patients treated with neoadjuvant chemotherapy after radical mastectomy. More importantly, this combined treatment can also reduce the long-term recurrence and metastasis of TNBC.

Association of Genetic Ancestry With Terminal Duct Lobular Unit Involution Among Healthy Women.

Reduced age-related terminal duct lobular unit (TDLU) involution has been linked to increased breast cancer risk and triple-negative breast cancer. Associations of TDLU involution levels with race and ethnicity remain incompletely explored. Herein, we examined the association between genetic ancestry and TDLU involution in normal breast tissue donated by 2014 healthy women in the United States. Women of African ancestry were more likely than European women to have increased TDLU counts (odds ratio [OR]trend = 1.36, 95% confidence interval [CI] = 1.07 to 1.74), acini counts per TDLU (OR = 1.47, 95% CI = 1.06 to 2.03), and median TDLU span (ORtrend = 1.44, 95% CI = 1.08 to 1.91), indicating lower involution, whereas East Asian descendants were associated with decreased TDLU counts (ORtrend = 0.52, 95% CI = 0.35 to 0.78) after controlling for potential confounders. These associations are consistent with the racial variations in incidence rates of triple-negative breast cancer in the United States and suggest opportunities for future work examining whether TDLU involution may mediate the racial differences in subtype-specific breast cancer risk.

Assessment of Suspected Breast Lesions in Early-Stage Triple-Negative Breast Cancer during Follow-Up after Breast-Conserving Surgery Using Multiparametric MRI.

Background The local recurrence rate of triple-negative breast cancer (TNBC) can be as high as 12%.The standard treatment for early-stage TNBC is breast-conserving surgery (BCS), followed by postoperative radiotherapy with or without chemotherapy. However, detection of the local recurrence of the disease after radiotherapy is a major issue. Objective The aim of this study was at investigating the role of dynamic and functional magnetic resonance imaging (MRI) during follow-up after BCS and radiotherapy with/without chemotherapy to differentiate between locoregional recurrence and postoperative fibrosis. Patients and Methods. This prospective study was conducted at the oncology, radiology, and pathology departments, Tanta University. It involved 50 patients with early-stage TNBC who were treated with BCS, followed by radiotherapy with/without chemotherapy. The suspected lesions were evaluated during the follow-up period by sonomammography. All patients were subjected to MRI, including conventional sequences, diffusion-weighted imaging (DWI), and dynamic postcontrast study. Results Ten cases were confirmed as recurrent malignant lesions. After contrast administration, they all exhibited irregular T1 hypodense lesions of variable morphology with diffusion restriction and positive enhancement. Eight cases displayed a type III curve, while two showed a type II curve. Histopathological assessment was consistent with the MRI findings in all eight cases. The combination of the data produced by DWI-MRI and dynamic contrast-enhanced (DCE) MRI resulted in 100%sensitivity, 92.5% specificity, 90.9% positive predictive value, 100% negative predictive value, and 98% accuracy. Conclusion Combination of DWI-MRI and DCE-MRI could have high diagnostic value for evaluating postoperative changes in patients with TNBC after BCS, followed by radiotherapy with/without chemotherapy. Trial Registrations. No trial to be registered.

Home mortgage discrimination and incidence of triple-negative and Luminal A breast cancer among non-Hispanic Black and non-Hispanic White females in California, 2006\u20132015

PurposeIn the United States, Black females are burdened by more aggressive subtypes and increased mortality from breast cancer compared to non-Hispanic (NH) White females. Institutional racism may contribute to these inequities. We aimed to characterize the association between home mortgage discrimination, a novel measure of institutional racism, and incidence of Luminal A and triple-negative breast cancer (TNBC) subtypes among NH Black and NH White females in California metropolitan areas.MethodsWe merged data from the California Cancer Registry on females aged 20 + diagnosed with primary invasive breast cancer between 2006 and 2015 with a census tract-level index of home mortgage lending bias measuring the odds of mortgage loan denial for Black versus White applicants, generated from the 2007–2013 Home Mortgage Disclosure Act database. Poisson regression estimated cross-sectional associations of census tract-level racial bias in mortgage lending with race/ethnicity- and Luminal A and TNBC-specific incidence rate ratios, adjusting for neighborhood confounders.ResultsWe identified n = 102,853 cases of Luminal A and n = 15,528 cases of TNBC over the study period. Compared to NH Whites, NH Black females had higher rates of TNBC, lower rates of Luminal A breast cancer, and lived in census tracts with less racial bias in home mortgage lending. There was no evidence of association between neighborhood racial bias in mortgage lending at the time of diagnosis and either subtype among either racial/ethnic group.ConclusionFuture research should incorporate residential history data with measures of institutional racism to improve estimation and inform policy interventions.

A Population Health Assessment in a Community Cancer Center Catchment Area: Triple-Negative Breast Cancer, Alcohol Use, and Obesity in New Castle County, Delaware.

The NCI requires designated cancer centers to conduct catchment area assessments to guide cancer control and prevention efforts designed to reduce the local cancer burden. We extended and adapted this approach to a community cancer center catchment area with elevated rates of triple-negative breast cancer (TNBC). Cancer registry data for 462 TNBC and 2,987 "Not-TNBC" cases diagnosed between 2012 and 2020 at the Helen F. Graham Cancer Center & Research Institute (HFGCCRI), located in New Castle County, Delaware, were geocoded to detect areas of elevated risk (hot spots) and decreased risk (cold spots). Next, electronic health record (EHR) data on obesity and alcohol use disorder (AUD) and catchment area measures of fast-food and alcohol retailers were used to assess for spatial relationships between TNBC hot spots and potentially modifiable risk factors. Two hot and two cold spots were identified for TNBC within the catchment area. The hot spots accounted for 11% of the catchment area but nearly a third of all TNBC cases. Higher rates of unhealthy alcohol use and obesity were observed within the hot spots. The use of spatial methods to analyze cancer registry and other secondary data sources can inform cancer control and prevention efforts within community cancer center catchment areas, where limited resources can preclude the collection of new primary data. Targeting community outreach and engagement activities to TNBC hot spots offers the potential to reduce the population-level burden of cancer efficiently and equitably.

Molecular targets and therapeutics in chemoresistance of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer (BC), which shows immunohistochemically negative expression of hormone receptor i.e., Estrogen receptor and Progesterone receptor along with the absence of Human Epidermal Growth Factor Receptor-2 (HER2/neu). In Indian scenario the prevalence of BC is 26.3%, whereas, in West Bengal the cases are of 18.4%. But the rate of TNBC has increased up to 31% and shows 27% of total BC. Conventional chemotherapy is effective only in the initial stages but with progression of the disease the effectivity gets reduced and shown almost no effect in later or advanced stages of TNBC. Thus, TNBC patients frequently develop resistance and metastasis, due to its peculiar triple-negative nature most of the hormonal therapies also fails. Development of chemoresistance may involve various factors, such as, TNBC heterogeneity, cancer stem cells (CSCs), signaling pathway deregulation, DNA repair mechanism, hypoxia, and other molecular factors. To overcome the challenges to treat TNBC various targets and molecules have been exploited including CSCs modulator, drug efflux transporters, hypoxic factors, apoptotic proteins, and regulatory signaling pathways. Moreover, to improve the targets and efficacy of treatments researchers are emphasizing on targeted therapy for TNBC. In this review, an effort has been made to focus on phenotypic and molecular variations in TNBC along with the role of conventional as well as newly identified pathways and strategies to overcome challenge of chemoresistance.

Cancer Progress and Priorities: Breast Cancer.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

Abstract SS1-07: Gene expression profiles of Ghanaian and Ethiopian triple-negative breast tumors

Abstract Background: Triple-negative breast cancer (TNBC) remains the most aggressive molecular subtype of breast cancer, with worse survival outcomes compared to other breast cancer subtypes. TNBC prevalence is highest among women of African descent worldwide, and through our previous work we have established a connection between West African ancestry (WAa) and higher rates of TNBC. Specifically, we have shown that prevalence rates of TNBC among West African and African American women are similar and higher than that of East African and White American women. We have also shown that quantified African ancestry is higher among TNBC cases compared to non-TNBC cases. To determine the influence African ancestry on the TNBC tumor environment, we sought to determine any differences in gene expression profiles of Ghanaian (West African) compared to Ethiopian (East African) women. Methods: RNA was extracted and sequenced from a pilot cohort of archival FFPE tumor tissue among Ghanaian (n = 19) and Ethiopian (n = 20) women. RNAseq reads were aligned, and quality of alignments were assessed, where de-duplicated samples with counts above 10M reads were included in the final analysis. Genetic ancestry was quantified by obtaining SNVs called from the RNAseq alignments, using GATK best practices. Differentially expressed genes lists were determined comparing Ghanaian vs. Ethiopian TNBC tumors, and also by identifying genes that were associated with increasing African ancestry. These gene lists, and log-fold change between comparison groups, were used as input for Ingenuity Pathway Analysis (IPA), to identify canonical pathways and de novo networks that are specific to Ghanaian or Ethiopian TNBC tumors. Results: Using 1KG populations as our reference to quantify genetic ancestry, we show that Ghanaian samples have &amp;gt;94% AFR ancestry, specifically matching population groups representative of WAa. The Ethiopian samples showed between 37-48% AFR ancestry, primarily represented by East African groups. Interestingly, there seems to be a significant proportion of EUR ancestry among the Ethiopians samples (30-49%), primarily represented by Italian ancestry. We have conducted the differential gene expression analysis in two ways. First, we have compared gene expression profiles between Ghanaian and Ethiopian tumors. In our preliminary analysis, we identified &amp;gt;600 genes (p &amp;lt; 0.01) that were differentially expressed between Ghanaian and Ethiopian TNBC tumors. Second, we used AFR ancestry as a continuous variable, where we conducted a linear regression analysis to identify genes associated with AFR ancestry. We identified &amp;gt;900 genes associated with AFR ancestry (p &amp;lt; 0.01), and this gene signature distinguished Ghanaian from Ethiopian tumors in an unsupervised hierarchical clustering. In comparing the differentially expressed gene lists from these two approaches, approximately 200 genes were shared, indicating the distinct value of both analyses. Using these gene lists as input for IPA analysis, we have begun to identify canonical pathways that have been altered by our differentially expressed genes, alongside de novo networks that differ between our Ghanaian and Ethiopian tumors. In our overlapping gene list, we see predicted differences in functions such as quantity of T lymphocytes, where genes downregulated in Ethiopian tumors may indicated reduced presence of these immune cells. Using CIBERSORT and xCell deconvolution methods, validation of these findings are ongoing. Conclusions and Ongoing work: This work highlights how ancestry-specific gene regulation can delineate differences in the tumor microenvironment among a cohort of African tumors. We are currently evaluating distribution of TNBC subtypes and estimation of immune cell populations in these tumors, to determine ancestry-specific differences in tumor heterogeneity and immune response. Citation Format: Rachel Martini, Endale Gebregzabher, Princesca Dorsaint, Timothy Chu, Kanika Arora, Lee Gibbs, Zarko Manojlovic, Nicolas Robine, Andrea Sboner, Olivier Elemento, John Carpten, Lisa Newman, Melissa Davis. Gene expression profiles of Ghanaian and Ethiopian triple-negative breast tumors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS1-07.

Abstract PS7-40: Triple negative breast cancer in New Orleans, part deux

Abstract Version 7/7/2020 with edit Triple-Negative Breast Cancer in New Orleans – part deaux Objectives: To update our previously reported findings with more current data from SEER 18 registries to compare race-specific incidence rates of triple-negative breast cancer (TNBC) in New Orleans (NO) and Louisiana (LA) with other SEER metro areas and identify the predictors of TNBC. Background: We previously reported significantly increased incidence rates of TNBC in black women (BW) in NO and LA than other SEER metro areas. Methods: We analyzed tumor characteristics of invasive female breast cancers diagnosed from 2011-2017 from SEER 18 for BW and white women (WW). We compared LA data with SEER 18 and metropolitan areas (Atlanta, Detroit, Los Angeles and San Francisco) as we did with our previous data set. Predictors of TNBC in NO and LA were identified in multivariate logistic regression adjusting for age, BMI, poverty, insurance, tumor size, Bloom-Richardson grade and AJCC stage. Results: The overall incidence rate of TNBC in BW was again significantly higher in NO (29.8 per 100,000) than any metro area and the SEER metro areas combined (23.9 per 100,000). Detroit again had the second highest rate (27.2) followed by San Francisco/Oakland (23.8) Los Angeles (22.3) and Atlanta (22.1). The multivariable analysis showed that younger age, large tumor size, high grade were associated with increased risk of TNBC in BW. Conclusions: The incidence rates of TNBC in BW in NO continue to be consistently higher compared to LA and other SEER 18 metro areas. This data reiterates the importance of ongoing translational research to broaden the understanding and optimize the treatment of this aggressive disease, especially in this vulnerable population. Citation Format: Michelle M Loch, Mei-Chin Hsieh, Thomas Reske, Vivien Chen, Xiao-Cheng Wu. Triple negative breast cancer in New Orleans, part deux [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-40.

Abstract IA26: Learning from and Addressing Racial and Ethnic Disparities in Cancer Clinical Trials: The ECOG-ACRIN Experience

Abstract Although breast cancer incidence and mortality have declined by about 35% in the United States since 1990, mortality rates have declined less in Black women, contributing to a widening of the racial gap which has contributed to about a 35% higher mortality rate for Black women compared with others. Black women are more likely to present with advanced stage disease, have triple negative breast cancer (TNBC), exhibit greater non-adherence and poorer tolerance to chemotherapy and endocrine therapy, and have more comorbidities and experience more disparities in care. With regard to ethnicity, Hispanic women also exhibit higher rates of TNBC, but otherwise experience similar outcomes as non-Hispanic women. In order to disentangle factors that may be contributing to inferior outcome associated with Black race, we evaluated the association between Black race or Hispanic ethnicity and recurrence in the population served by Montefiore Medical Center and in 3 clinical trials (E1199, E5103, TAILORx) coordinated by the ECOG-ACRIN Cancer Research Group, as summarized in Table 1. The results were remarkably consistent – Black race was associated with significantly higher recurrence risk (1.39-1.84-fold) in multivariate models in ER+ breast cancer, but not ER-negative breast cancer. Similar findings were not observed for Hispanic women. In the TAILORx trial, there were no significant differences in distribution of 21-gene recurrence score, nor ER, PR, or HER2 RNA expression levels, by race or ethnicity. In other analysis, we have reported specific genetic variants associated with higher risk of taxane-induced neuropathy in Black women (PMID: 26138065). Our findings highlight the need for greater representation of racial and ethnic minorities in clinical trials, and that additional studies designed specifically to determine if socioeconomic factors, biological factors, and/or other factors contribute to these disparities. ECOG-ACRIN is currently conducting a clinical trial to prospectively validate genetic variants associated with higher risk of peripheral neuropathy in Black women with breast cancer receiving taxane therapy (EAZ171; NCT04001829). Citation Format: Joseph A. Sparano. Learning from and Addressing Racial and Ethnic Disparities in Cancer Clinical Trials: The ECOG-ACRIN Experience [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA26.

Abstract PO-153: Triple negative breast cancer (TNBC) in Indiana: A population-based cohort study from the Indiana Cancer Registry

Abstract Background: TNBC has a poor prognosis compared to estrogen receptor (ER) and HER2 positive breast cancer, yet its etiology is unclear. Despite having a low incidence of all breast cancers, Indiana (IN) has a diverse socioeconomic, racial, concentrate urban/rural makeup, and thus provides a perfect study population to explore the etiology of TNBC through investigating the occurrence based on the geographical and demographical incidences in the state. Methods: Cancer registry data from the State Department of Health was used to examine the incidence, characteristics, and distribution of TNBC across the state of Indiana. TNBC cases were identified as those with negative ER, progesterone (PR), and HER2 status; whereas controls were positive for any of the three receptors. During 2010-2015, 19,267 invasive breast cancer cases had receptor status available for this analysis. Covariables such as age, tumor biology, and breast cancer subtypes were evaluated by multiple t-tests and chi-squared testing. To compare the occurrence of TNBC among different ages and races within a specific area, the 5-year Standard Incidence Ratio (SIR) was used and ratios over one signify the percentage above the expected number of cases. SIR was calculated by dividing observed cases by expected cases during the study period. To obtain the expected number of cases the highest NCI SEER all ages all race incidence rates 2000-2016 was used, as no state incidence rates for TNBC are available. Results: Indiana has 15% greater (p= 1.54E-13) incidence of TNBC compared to the nation. The age-adjusted incidence of TNBC broken down to the county level verified 59% of counties having rates above the national rate of 13.9. Nearly one third (28%) of TNBC incidence, were in Lake (Southeast of Chicago) and Marion (Indianapolis) counties. These are the most populated, urban, and racially diverse counties in IN. SIRs for both counties were remarkably higher than expected. Moreover, in Marion and Lake, the Black-specific SIR for TNBC was 1.4 (p=5E-6) and 1.7 (p=2.494E-8) while the Caucasian-specific SIR was 1.3 (p=1E-6) and 1.3 (p=9E-4). Analysis of specific zip codes within each county revealed clustered areas with extremely high SIRs, ranging from 2 to 238% above expected. Conclusion: Our results demonstrated significantly higher incidence rates of TNBC in Indiana. The highest age-adjusted incidence of TNBC was focused around urban, industrial, low income, heavily African American zip codes. This aligns with work by Downey et al which describes a highly significant 1.76 increased toxic concentration ratio exposure for Blacks compared to Whites in Indianapolis/Marion County (2007). Higher than expected ratios for both races implies that environmental exposures could be contributing to an increased incidence. This is the first study to show the geographical clustering of TNBC incidence, primarily around highly urban areas. Citation Format: Casey L. Bales, Fei Shen, Guanglong Jiang, Walker Nurrenbern, Jaqueline Flores, Bryan Schneider, Tim McFarlane. Triple negative breast cancer (TNBC) in Indiana: A population-based cohort study from the Indiana Cancer Registry [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-153.