Molecular Characteristics Of Breast Cancer Research Articles

An Investigation on Breast Cancer Knowledge in Developing Nations

The most common malignant tumor in women diagnosed globally, breast cancer is the leading cause of cancer-related death. Globally, the prevalence of breast cancer is continuously increasing. Breast cancer is the most prevalent type of cancer in the world. Hereditary and genetic predispositions are among the risk factors linked to the incidence of breast cancer. Breast cancers come in a wide variety of forms. The molecular characteristics of breast cancer, including hormone receptor activation (PR, ER, and HER2) and human epidermal growth factor receptor 2 (HER2), genetic changes (BRCA1/2 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [PIK3CA] mutations), and immune system markers (PD L1, tumour-infiltrating lymphocytes [TIL], and programmed death-ligand 1 [PD L1]) may impact treatment approaches.

An Investigation on Breast Cancer Knowledge in Developing Nations

Breast cancer is the most common malignant tumor in women diagnosed globally and the leading cause of cancer-related death. Globally, the prevalence of breast cancer is increasing with time. Globally, breast cancer is the most prevalent type of cancer. The incidence of breast cancer is linked to several risk factors, such as genetic and inherited predispositions. Breast cancers can be of many different forms. The molecular features of breast cancer, such as the activation of hormone receptors (PR, ER, and HER2) and human epidermal growth factor receptor 2, genetic alterations (BRCA1/2 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [PIK3CA] mutations), and immune system markers (PD L1, tumour-infiltrating lymphocytes [TIL], and programmed death-ligand 1 [PD L1]) may impact treatment strategies. sufferers.

Exploring human mammaglobin: as a possible diagnostic and prognostic indicator in breast cancer tissue

Breast cancer is a major global health issue, with high diagnosis rates worldwide, especially in less developed areas, leading to significant mortality rates. This review focuses on the molecular characteristics of breast cancer, emphasizing the role of human mammaglobin-A (hMAM-A) as a diagnostic and prognostic marker. hMAM-A, a dimeric protein from the secretoglobin family, is produced exclusively by breast tissue and shows elevated levels in breast cancer cases, making it a highly accurate marker for disease detection. The review also examines various factors influencing breast cancer, such as age, tobacco use, menopausal status, and hormone replacement therapy (HRT). Younger age at diagnosis is associated with poorer outcomes, highlighting the importance of early detection. Tobacco smoke increases mortality rates in breast cancer patients. Menopausal status affects molecular subtypes and risk factors, impacting treatment and prognosis. HRT has a complex relationship with breast cancer risk. The review concludes by discussing the need for novel biomarkers, including hMAM-A, to improve breast cancer diagnosis and management.

Breast Cancer Classification by Gene Expression Analysis using Hybrid Feature Selection and Hyper-heuristic Adaptive Universum Support Vector Machine

Comprehensive assessments of the molecular characteristics of breast cancer from gene expression patterns can aid in the early identification and treatment of tumor patients. The enormous scale of gene expression data obtained through microarray sequencing increases the difficulty of training the classifier due to large-scale features. Selecting pivotal gene features can minimize high dimensionality and the classifier complexity with improved breast cancer detection accuracy. However, traditional filter and wrapper-based selection methods have scalability and adaptability issues in handling complex gene features. This paper presents a hybrid feature selection method of Mutual Information Maximization - Improved Moth Flame Optimization (MIM-IMFO) for gene selection along with an advanced Hyper-heuristic Adaptive Universum Support classification model Vector Machine (HH-AUSVM) to improve cancer detection rates. The hybrid gene selection method is developed by performing filter-based selection using MIM in the first stage followed by the wrapper method in the second stage, to obtain the pivotal features and remove the inappropriate ones. This method improves standard MFO by a hybrid exploration/exploitation phase to accomplish a better trade-off between exploration and exploitation phases. The classifier HH-AUSVM is formulated by integrating the Adaptive Universum learning approach to the hyper- heuristics-based parameter optimized SVM to tackle the class samples imbalance problem. Evaluated on breast cancer gene expression datasets from Mendeley Data Repository, this proposed MIM-IMFO gene selection-based HH-AUSVM classification approach provided better breast cancer detection with high accuracies of 95.67%, 96.52%, 97.97% and 95.5% and less processing time of 4.28, 3.17, 9.45 and 6.31 seconds, respectively.

Female Breast Cancer in Northern Ghana: A Retrospective Histopathological Study at the Department of Pathology of the Tamale Teaching Hospital (TTH) (2012 To 2021)

Background: Data on breast cancer (BC) in northern Ghana is scant. The aim of this study was to provide data on the clinicopathological, prognostic and molecular characteristics of BC in females of northern Ghana. Methods: Data on breast cancer patients (n = 1,913) in the Department of Pathology of the Tamale Teaching Hospital (TTH) was collected from 1st January, 2012 to 31st December, 2021 and analysed at four levels: introduction, clinico-pathological features, prognostic stratification using the NPI score and the molecular subtypes of BC based on IHC Status. Associations between variables were determined by Fisher’s exact test. Results: There were 1,191 (62.3%) benign and 722 (37.7%) malignant tumors. A gradual rise in the relative proportions of the female BCs over the period was observed. The mean age (years) of BCs diagnosed in small to medium size samples was 47.7±16.0, and 36.4% were aged <40 years. The commonest clinical presentation of BC was a palpable breast lump (65.5%). Majority of the BC patients presented 3 months after the onset of the illness. Invasive ductal carcinoma was the commonest subtype of BC (78.0%), and the great majority (93.1%) had a combined (II & III) high histological grade (P<0.0001). Stratifying women diagnosed with BC into prognostic categories using the NPI, 15.4% had excellent prognosis, compared to 49.2% with poor prognosis. Conclusion: The study identified breast cancer as a common breast disease among women in the study area with advanced clinico-pathological features at presentation, and therefore, poor prognosis even at the time of diagnosis.

The role of HER2 alterations in clinicopathological and molecular characteristics of breast cancer and HER2-targeted therapies: a comprehensive review.

Breast cancer (BC) is the most common malignancy in women and one of the leading causes of cancer mortality, despite significant treatment advancements over the last decades. Human epidermal growth factor receptor-2 (HER2) is a member of the ERBB family of receptor tyrosine kinases which have long been known to mediate cancer cell growth and invasion through constitutive activation of oncogenic downstream signaling, such as PI3K/Akt/mTOR and MAPK. Overexpression/amplification of HER2 in various tumors, especially BC, offers the possible therapeutic potential for target therapies. HER2-targeted therapies, either with a combination of chemotherapy or through multi-anti-HER2 therapies without chemotherapy, have significantly improved the prognosis of HER2-positive tumors. In recent years, novel anti-HER2 agents and combination therapies have garnered much attention, especially for heavily treated advanced or metastatic BCs. HER2-positive BC is biologically a heterogeneous group depending on HER2 activation mechanisms, hormone receptor status, genome variations, tumor heterogeneity, and treatment resistance, which affect the treatment benefit and patients' outcomes. This review will discuss HER2 alternations (gene amplification or receptor overexpression) in BC, their correlation with clinicopathological characteristics and molecular characteristics, and HER2-based therapies in tumors with HER2 overexpression/amplification.

Phospholipid Mediator Induced Transformation in Three-Dimensional Cultures.

Several models have been developed to study cancer, such as rodent models and established cell lines. Valuable insights into carcinogenesis have been provided by studies using these models. Cell lines have provided an understanding of the deregulation of molecular signaling associated with breast tumorigenesis, while rodent models are widely used to study cellular and molecular characteristics of breast cancer in vivo. The establishment of 3D cultures of breast epithelial and cancerous cells aids in bridging the gap between in vivo and in vitro models by mimicking the in vivo conditions in vitro. This model can be used to understand the deregulation of complex molecular signaling events and the cellular characteristics during breast carcinogenesis. Here, a 3D culture system is modified to study a phospholipid mediator-induced (Platelet Activating Factor, PAF) transformation. Immunomodulators and other secreted molecules play a major role in tumor initiation and progression in the breast. In the present study, 3D acinar cultures of breast epithelial cells are exposed to PAF exhibited transformation characteristics such as loss of polarity and altered cellular characteristics. This 3D culture system will assist in shedding light on genetic and/or epigenetic perturbations induced by various small molecule entities in the tumor microenvironment. Additionally, this system will also provide a platform for the identification of novel as well as known genes that may be involved in the process of transformation.

Quantitative analysis of breast cancer tissue composition and associations with tumor subtype

The tumor microenvironment is an important determinant of breast cancer progression, but standard methods for describing the tumor microenvironment are lacking. Measures of microenvironment composition such as stromal area and immune infiltrate are labor-intensive and few large studies have systematically collected this data. However, digital histologic approaches are becoming more widely available, allowing high-throughput, quantitative estimation. We applied such methods to tissue microarrays of tumors from 1687 women (mean 4 cores per case) in the Carolina Breast Cancer Study Phase 3. Tumor composition was quantified as percentage of epithelium, stroma, adipose, and lymphocytic infiltrate (with the latter as presence/absence using a ≥1% cutoff). Composition proportions and presence/absence were evaluated in association with clinical and molecular features of breast cancer (intrinsic subtype and RNA-based risk of recurrence [ROR] scores) using multivariable linear and logistic regression. Lower stromal content was associated with aggressive tumor phenotypes, including triple-negative (31.1% vs. 41.6% in HR+/HER2-; RFD [95% CI]: -10.5%, [-13.1, -7.9]), Basal-like subtypes (29.0% vs. 44.0% in Luminal A; RFD [95% CI]: -14.9%, [-17.8, -12.0]), and high RNA-based PAM50 ROR scores (27.6% vs. 48.1% in ROR low; RFD [95% CI]: -20.5%, [24.3, 16.7]), after adjusting for age and race. HER2+ tumors also had lower stromal content, particularly among RNA-based HER2-enriched (35.2% vs. 44.0% in Luminal A; RFD [95% CI]: -8.8%, [-13.8, -3.8]). Similar associations were observed between immune infiltrate and tumor phenotypes. Quantitative digital image analysis of the breast cancer microenvironment showed significant associations with demographic characteristics and biological indicators of aggressive behavior.

Abstract P3-14-12: Distinct and targetable molecular features of breast cancer in African American women

Abstract Introduction: Despite having a lower incidence of breast cancer, African American (AA) women suffer disproportionately worse outcomes; with more aggressive cancer and higher mortality rates, as well as higher incidence of triple negative breast cancer (TNBC). The cause of these disparities is unclear, but may be driven by different biologic and molecular features. Information about targetable molecular profiles for breast cancer in AAs is limited, and may not be representative of racial minorities. A better understanding of actionable targets is needed to improve treatment and outcomes of breast cancer for AA women. Materials and methods: This study utilized molecular data from three TCGA Breast Invasive Carcinoma studies (Cell 2015, Firehose Legacy, and PanCancer Atlas) on CBioPortal. Data was stratified by C/White and AA/Black to identify the most commonly affected genes, the most significantly differentially affected genes between the two populations, and 35 actionable genes. Genes were compared between racial subgroups (455 AA cases, 2103 C cases) for analysis of mutation types (point mutations, splice site, deletions, and amplifications) mutation load, overall survival, and mRNA expression vs. copy number variation (CNV). Data was assessed for differences, with p-value set at <0.05, and OncoPrints generated using tools in CBioPortal. Results: 2282 genes were differentially altered between white and black subgroups (P<0.05). Of the most commonly altered genes, only three were significantly different between AA and C: TP53, PIK3CA, and CSMD1 (p<0.001). PIK3CA missense mutations were more common in C (36.28% (C) vs 22.47% in AA). TP53 missense mutations were more prevalent in AA (40.09% vs. 28.58% in C). CSMD1 deletions, a tumor suppressor gene, were more prevalent in AA (19.78%) vs. 10.79% in C. We identified a cluster of genes at 8q24.21 (MYC, CASC8, POU51B, CCAT2) showing frequent co amplification in AA and C. For TNBC cases (18 AA cases, 52 C cases), the alteration rate of following genes was significantly between AA and C groups USF3 (27.8% in AA, 0% in C); PIK3C2B (27.8% AA, 1.9% C); SLC41A1 (27.8% AA, 3.85% C); PDHX, PRICKLE4, TOMM6 (all 27.8% AA, 5.8% C); and EHF and PRPF4B (both 27.8% AA, 7.7% C). Some of the genes with highest frequency in both groups include: TP53 (83.3% in AA, 78.9% C); PVT1 (38.9% AA, 46.2% C); CASC8, MYC, and POU51B (33.3% AA, 46.2% C). For actionable targets, PIK3CA, RAD51B, MSH6, KRAS, and NTRK3 were significantly different between AA and C (p<0.05). Of note, FGFR1 and NTRK1 amplifications were common in both AA and C subgroups, 17% AA/13% C and 15% AA/11% C respectively, and are potential targets for emerging therapeutics. Of note, TTN missense mutations were common in both subgroups (15.93% in AA and 18.11% in C), and may be an important marker of tumor mutational burden and predictive for immunotherapy responsiveness. ERBB2 was also commonly amplified in both groups (14% in AA and 12% in C). Survival analysis showed significantly worse outcomes for AA women with PIK3CA alterations (50% disease free for PIK3CA vs. 75% for unaltered at 75 months), while C women with PIK3CA alterations had improved outcomes (85% disease free for PIK3CA vs. 80% for unaltered at 75 months). Conclusion: Significant and diverse molecular differences exist in breast cancer between AA vs. C subgroups. Many of these molecular alterations are linked to specific treatment opportunities. The results indicate that comprehensive molecular profiling may have a major role in assessing treatments for patients with breast cancer, and that AA women may develop breast tumors with unique molecular features requiring novel treatment strategies. Citation Format: Genevra Magliocco, Roy Khalife, Anthony Magliocco. Distinct and targetable molecular features of breast cancer in African American women [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 P3-14-12.

Abstract 608: Molecular features of breast cancer involved in classification and prognosis of a multi-country Latin American cohort: The US-LACRN-MPBCS breast cancer cohort

Abstract Although gene expression-derived PAM50 intrinsic subtypes (LumA, LumB, HER2E and Basal) were reported in Latin American breast cancer, most studies did not adequately represent the unique and diverse genetic admixture of the Latin American population and/or included a small number of individuals. As a result of these limitations, confirmation of the prognostic value of available intrinsic subtype classification signatures in a diverse cohort of Latin American women is of utmost importance. We assessed the general distribution and prognostic performance of PAM50-based intrinsic and immunohistochemistry (IHC)-based surrogate subtype classifications in Latin American women included in the Molecular Profile of Breast Cancer Study (MPBCS), an initiative of the US-Latin America Cancer Research Network (US-LACRN) comprising institutions of Argentina, Brazil, Chile, Mexico and Uruguay. MPBCS focused on stage II-III breast cancer in Latin American women. Eligible enrolled patients (n=1300) were characterized clinically, pathologically and epidemiologically and followed-up for 5 years. IHC subtypes were assessed according to St Gallen's 2013 criteria, using Ki67 to discriminate LumB from LumA tumors. A total of 1071 tumors were characterized by gene-expression microarrays. PAM50 classification defined 45% of tumors as LumA, 19.7% as LumB, 13.8% as HER2E and 17.5% as Basal. Normal-like tumors (6.3%) were excluded from the analysis. The 5-year prognostic ability of PAM50 and IHC classifications, both at the cancer-specific (OS) and progression-free survival (PFS), was tested. The prognosis for LumA tumors was significantly better than for other subtypes, while Basal-like tumors had the worst prognosis. The prognostic power of IHC-based subtypes (C-index 0.698 for OS, 0.635 for PFS) was very similar to that of PAM50 (C-index 0.678 for OS, 0.639 for PFS), indicating that in US-LACRN-MPBCS, contrary to other cohorts, surrogate subtypes are as useful as PAM50 for discriminating recurrence risk. PAM50-derived risks of recurrence (RORs), in particular ROR-S (C-index 0.699 for OS, 0.649 for PFS), clearly discriminated risk into low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Overall, a general concordance of the molecular features of US-LACRN-MPBCS breast cancer tumors with those of other cohorts was confirmed. The shift towards non-luminal subtypes could be partly attributable to the recruitment bias towards advanced stages. Further refinement of analyses using molecular ancestry assignation may help to reveal more subtle differences in this heterogeneously admixed population. Citation Format: Andrea S. Llera, Eliana Abdelhay, Osvaldo Podhajcer, Nora Artagaveytia, Adrián Daneri-Navarro, Bettina Müller, Carlos Velázquez Contreras, Darío Rocha, Juan Martín Sendoya, Renata Binato, Elmer Fernández, Elsa Alcoba, Isabel Alonso, Alicia I. Bravo, Natalia Camejo, Dirce Carraro, Mónica Castro, Juan M. Castro-Cervantes, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Susanne Crocamo, Raul Delgadillo-Cisterna, Lucía Delgado, Alicia del Toro Arreola, Marisa Dreyer Breitenbach, Jorge Fernández, Wanda Fernández, Ramon A. Franco-Topete, Fancy Gaete, Jorge Gómez, Gonzalo Greif, Marisol Guerrero, Marianne Marianne Henderson, Andres de J Moran-Mendoza, María Aparecida Nagai, Antonio Oceguera-Villanueva, Antonio Quintero-Ramos, Rui Reis, Javier Retamales, Robinson Rodríguez, Cristina Rosales, Efrain Salas-González, Laura Segovia, Araceli Silva-García, Vidya Vedham, Livia Zagame, The US-Latin American Cancer Research Network. Molecular features of breast cancer involved in classification and prognosis of a multi-country Latin American cohort: The US-LACRN-MPBCS breast cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 608.

Uncovering the Subtype-Specific Molecular Characteristics of Breast Cancer by Multiomics Analysis of Prognosis-Associated Genes, Driver Genes, Signaling Pathways, and Immune Activity.

Breast cancer is a heterogeneous malignant disease with different prognoses and has been divided into four molecular subtypes. It is believed that molecular events occurring in breast stem/progenitor cells contribute to the carcinogenesis and development of different breast cancer subtypes. However, these subtype-specific molecular characteristics are largely unknown. In this study, we employed 1217 breast cancer samples from The Cancer Genome Atlas (TCGA) database for a multiomics analysis of the molecular characteristics of different breast cancer subtypes based on PAM50 algorithms. We detected the expression changes of subtype-specific genes and revealed that the expression of particular subtype-specific genes significantly affected prognosis. We also investigated the mutations and copy number variations (CNVs) of breast cancer driver genes and the representative genes of ten signaling pathways in different subtypes and revealed several subtype-specifically altered genes. Moreover, we detected the infiltration of various immune cells in different subtypes of breast cancer and showed that the infiltration levels of major immune cell types are different among these subtypes. Additionally, we investigated the factors affecting the immune infiltration level and the immune cytolytic activity in different breast cancer subtypes, namely, the mutation burden, genome instability and cancer-associated fibroblast (CAF) infiltration. This study may shed light on the molecular events contributing to carcinogenesis and development and provide potential markers and targets for the clinical diagnosis and treatment of different breast cancer subtypes.

Abstract 887: Clinicopathological and genetic features of breast cancer in Algerian population: A multicenter study

Abstract Background: Breast cancer is the most commonly diagnosed cancer and the leading cause of morbidity and mortality among Algerian women.The objective of this retrospective cohort study was to analyze some clinicopathological and molecular characteristics of breast cancer diagnosed between 2011 and 2019. Here we also report the experience of our research laboratory for the screening of BRCA1 and BRCA2 genes in hereditary breast and ovarian cancer (HBOC) patients. Materials and Methods: The population study included 7655 consecutive breast cancer patients. Data were collected from cancer registries of three medical oncology services and two anti-cancer centers located in north central region and eastern region of Algeria, respectively. Breast cancers were diagnosed between 2011 and 2019. Patient and tumor information included: age at diagnosis, menopausal status, receptor status, Ki-67 score, histological type,TNM stage and histological grade. Recurrent germline mutations on BRCA1 and BRCA2 genes previously found in Algerian patients were screened using PCR-Sanger sequencing in 230 HBOC patients. In addition, 18 HBOC patients were analyzed by NGS using a cancer panel of 30 hereditary cancer genes or BRCA1/2 genetic test. Results: The median age at diagnosis of the patients was 49.52 years. Data for age at diagnosis were available for 7389 patients. 55.29% patients were diagnosed under the age of 50 years and 55.83% had a premenopausal status. Data for receptor status were available for a total of 5599 patients. Of these, 55.75% patients were luminal A, 19.79% were TNBC, 17.39% were luminal B and 7.05% were HER2+. Data for Ki-67 score were available for 3357 cases. We noticed that 62.73% patients had a Ki-67 score ≥ 20% and 37.27% had a score <20%. Data for histological tumor type were available for 6145 cases. 84.28% patients had invasive ductal carcinoma followed by 8.84% with invasive lobular carcinoma. Data for TNM stage were available for 3524 cases. We identified 59.3% patients with stage III, 22.3% with stage II and 9.5% with stage IV. Data for histological grade were available for 6693 patients. We found 67.45% patients with grade II and 25.51% with grade III, respectively. 10 distinct BRCA1 germline mutations have been detected in 18 families and 5 distinct BRCA2 germline mutations have been identified in 5 families. The BRCA1 recurrent mutation c.83_84delTG has been detected in 5 unrelated families.The BRCA1 recurrent mutation c.2125_2126insA has been identified in 3 unrelated families. In addition, the BRCA1 c.181T>G has been found in two unrelated families. Interestingly, our results also showed differences in the distribution of the mutation spectrum of BRCA1 and BRCA2 genes between the eastern region and the north central region of Algeria. Conclusion: Our current study will contribute in developing optimal clinical trial protocols and personalized management strategies for breast cancer patients. Citation Format: Farid Cherbal, Leticia Ledmila Saada, Massila Nehar, Kamelia Yatta, Lydia Souha Zerrouki, Wafa Abdou, Chiraz Mehemmai, Hadjer Gaceb, Wassila Benbrahim, Hassen Mahfouf, Kada Boualga. Clinicopathological and genetic features of breast cancer in Algerian population: A multicenter study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 887.

Correlation of Primary Tumor Metabolic Parameters with Clinical, Histopathological and Molecular Characteristics in Breast Cancer Patients at Preoperative Staging FDG-PET/CT Study

Introduction: The aim of this prospective study was to evaluate the correlation of primary (1ry)tumor metabolic activity parameters maximum standardized uptake value (SUVmax) and tumor SUVmax/liver average SUV ratio (TLR) in initial staging 18F-fluorodeoxyglucose (FDG) positron emission tomography / computerized tomography (PET/CT) scan with clinical, histopathological and molecular characteristics of breast cancer (BC) patients. Material and Methods: Initial staging PET/CT was performed in 40 cases with different stages of BC in the supine position. Tumor FDG uptake was qualitatively evaluated and quantitatively assessed using SUVmax and TLR. Results: Forty female patients with newly diagnosed BC were enrolled in our study, age range from 31-78 (mean 50.5 +/- SD11.7). All the 1ry tumors were detected with mean SUVmax 10.8(+/-SD 7.9). The mean /median SUVmax values of 1ry tumor was higher in premenopausal, stage III& IV, Estrogen Receptors negative(ER-), Progesteron Receptors negative(PR-), Her2neu positive patients, high nuclear grade (GIII), in triple negative molecular subgroup (TN), positive axillary nodal (ALNs)metastases, and (P value = 0.003, 0.017, 0.113, 0.089 0.01,0.002, 0.007 & 0.016 respectively). The mean/median TLR values was higher in premenopausal and Her2neu positive, GIII, TN molecular subtype patients, stage III& IV and in patients with positive ALNs, ER- &PR - patients (P value = 0.002, 0.0476, 0.005, 0.018, 0.039 and 0.022, 0.095 & 0.129 respectively). SUVmax of the 1ry lesion and TLR were moderately negatively correlated with the age of the patients (P value = 0.005 and 0.008 respectively), also they were moderately positively correlated with the size of the1ry tumor (P value = 0.019 and 0.036 respectively). Conclusion: The SUVmax of the 1ry tumor and TLR values had similar significant associations with different prognostic factors in BC

Comprehensive omic characterization of breast cancer in Mexican-Hispanic women

Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1E17K hotspot mutation in 8% of the HM women and identify the AKT1/PIK3CA axis as a potentially druggable target. Also, HM luminal breast tumors present an enhanced immunogenic phenotype compared to Asiatic and Caucasian tumors. This study is an initial effort to include patients from Hispanic populations in the research of breast cancer etiology and biology to further understand breast cancer disparities.

Prevalence and prognosis of molecular phenotypes in breast cancer patients by age: a population-based retrospective cohort study in western Algeria.

Introductionbreast cancer is related to age. The young age remains a controversial issue as a prognostic factor and have more aggressive clinical behavior with poor outcome. We aimed for the first time in Algeria to explore on a large cohort of patients the prevalence of the molecular phenotypes and to describe their clinical characteristics and survival.Methodsmedical record of 1140 Algerian patients were analysed and categorized into three age groups: “young” when women were aged below 40 years; “middle-age” when women were aged from 41 to 54 years old and “elder” when women were over 54 years. Baseline categorical variables were analysed using the Chi-square test and survival curves were constructed using Kaplan Meir method.Resultsthe distribution of the various prognostic factors did not differ significativelly by age groups except for histological types, hormone receptors status and molecular phenotypes. Most patients were luminal A, indeed, young and intermediate age patients were most likely to be luminal A whereas the aged patients were triple negative with the highest mean DFS. Elsewhere young women are considered as human epidermal growth factor receptor 2 (HER2+) or triple negative molecular subtypes involving more rigorous therapeutic monitoring. The high rate of triple negative breast cancer in aged patients may due to genetic predispositions.Conclusionthis study sheds light on the histoclinical and molecular characteristics of breast cancer in young patients, which has a good prognosis than their older counterparts. Our results are therefore surprisingly different from what the literature suggests. A further study should understand this uncommon finding.

Clinic, pathologic and molecular landscapes in ultra-young women with breast cancer in the State of São Paulo: a real-world study

Introduction: Breast cancer (BC) centers are increasingly attending “ultra-young” women (UYW) patients (≤ 30 years), who usually present aggressive tumors and face specific problems. Objectives: We aimed to examine a multicentric casuistic view, addressing clinicopathological and molecular characteristics of BC, as well as therapeutic measures and oncological outcomes. Methods: A retrospective multicentric observational study of UYW with infiltrating BC was carried out. The patients were treated between the period from January 1991 to December 2019. Clinical, epidemiological, morphological, molecular, therapeutic and outcomes data were collected from the charts. Results: A total of 293 patients were followed for a average period of 34.5 months. Nulliparity was referred by 204 women (75.5%), of whom 81 (37.1%) were overweight or obese. Positive family history in first-degree relatives was verified in 25 patients (10.1%). Only 30 patients underwent genetic tests, which revealed inherited pathogenic mutations in 12 of them (37.5%). Thirty-two (32) cases were classified as T1 at diagnosis (10.9%), while “De novo” stage IV was found in 29 patients (9.8%). Mastectomy was performed in 175 women (70.2%), quadrantectomy in 46 women (18.4%), and mammary adenectomies in 28 women (11.2%), of which 149 cases were reported after neoadjuvant chemotherapy (56.0%). A total of 111 patients had at least one positive lymph node (47.4%). The rate of patients with estrogen receptor-negative was 32.7% and the rate of patients with Human Epidermal Growth Factor Receptor 2-positive (HER2-positive) was 25%. The frequency of Luminal A neoplasias was 16.6%, Luminal B/HER2- was 35.9%, Luminal B/HER2+ was 15.1%, HER2 overexpressed was 9.3%, and Basal was 22.9%. Taking into account the outcomes, 173 patients were alive without disease (65.7%); 23 patients were alive with any form of recurrence (8.7%); and 67 patients (25.4%) evolved to BC deaths. Conclusions: It was concluded that UYW with BC are commonly diagnosed at advanced stages, present adverse morphological and molecular parameters, and have unfavorable prognosis.

Abstract PO-220: Comprehensive "omic" portraits of breast cancer in Mexican-Hispanic women

Abstract Breast cancer is a relevant public health problem that affects millions of women worldwide. Breast tumors are recognized as a clinically and molecular heterogeneous pathology, but the genomic basis of its variability remains poorly understood, mainly regarding the comprehensive of ethnicity/racial disparities and their consequences in genomics studies. Moreover, most of the comprehensive molecular characterizations are predominantly centered on Caucasian population. Thus, we deeply characterized the molecular architecture of breast cancer in a set of Mexican patients through genomic and transcriptomic portraits. We explored the molecular features of breast cancers in Mexican-Hispanic (HM) women and compared them with public multi-ethnic datasets. HM patients presented an earlier onset of the disease, in particular in the aggressive Basal-like/triple negative and Luminal B subtypes. The significant E17K hotspot mutation in AKT1 gene occurred in 8% of the HM tumors, an enriched prevalence exclusively seen in this dataset. An integrative analysis also revealed an important role of the AKT1/PIK3CA axis as a potentially druggable target and indicate an aggressive biology. Computational analysis allowed us to identify age-related COSMIC (v2) signature 1 to be present in a much broader spectrum of HM women than in those from other ethnicities. On the basis of transcriptome immunogenomic analysis across human population we identified that luminal breast tumors with HM ancestry presented an enhanced immunogenic phenotype than their Asiatic and Caucasian counterparts. To the best of our knowledge, this dataset represents the largest breast cancer genomics characterization of breast tumors in Mexican women, and, provides novel insights into molecular phenotypes and mechanisms underlying carcinogenesis in a group of Mexican Hispanic women. In conclusion, this study provides a conceptual framework to better understand ethnic disparities of breast cancer. Citation Format: Sandra Lorena Romero-Cordoba, Ivan Salido-Guadarrama, Rosa Rebollar-Vega, Alberto Tenorio-Flores, Verónica Bautista-Piña, Felipe Villegas-Carlos, Carlos Dominguez-Reyes, Alfredo Hidalgo-Miranda. Comprehensive "omic" portraits of breast cancer in Mexican-Hispanic women [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-220.

Underexpression of circulating miR-145-5p and miR-133a-3p are associated with breast cancer and immunohistochemical markers.

MicroRNAs (miRNAs) are involved in the regulation of genes with important roles in cancer. Therefore, they represent interesting targets as biomarkers for early detection, follow-up, and prognosis of the disease. In early stages of breast cancer, differences in the expression of miR-148b-3p, miR-145-5p and miR-133a-3p have been reported. To compare the expression of miR-148b-3p, miR-145-5p and miR-133a-3p in serum samples from female patients with and without breast cancer. Case control study. We quantified the expression by real-time polymerase chain reaction of miR-148b-3p, miR-145-5p, and miR-133a-3p in serum samples from 27 breast cancer (BC) and 17 benign breast tumor patients. Comparison between groups with categorical variables was made using the Pearson's Chi-square test. Comparative analysis for continuous variables between two groups was performed using the Student's t-test. One-way analysis of variance (ANOVA) was used for multigroup comparison, followed by Tukey HSD analysis. The use of contraceptives and a high number of births were identified as risk factors for BC. We observed that miR-145-5p expresses in low levels in BC and positively diagnosed Her2 patients. In addition, BC patients with either ductal carcinoma or positive molecular diagnosis for estrogen receptor, progesterone receptor, luminal A, or Her2 negative, presented a decreased expression of miR-133a-3p. We observed an existing association between the molecular characteristics of BC and levels of circulating miR-133a-3p and miR-145-5p, proving the potential role of miRNAs as biomarkers for BC.

Abstract 4184: Tumor and risk factor characteristics among breast cancer patients from different geographic regions in Peru

Abstract There are few Latin American cohorts with available biospecimens that include women of high Indigenous American ancestry. The Peruvian population is characterized by a high degree of Native American (NA) ancestry, with this ancestral component varying between 56 to 100% on average, depending on the region. We have collected 1199 Peruvian samples from the Instituto Nacional de Enfermedades Neoplasicas in Lima. This cohort of patients represents a unique opportunity to study the molecular characteristics of breast cancer in the NA genetic and genomic background. Here we present a basic description of the women in the study and a comparison of tumor subtypes distribution and risk factor information of the patients by place of birth and residence. We explored differences in tumor subtype distribution and risk factors in relation to place of birth or residence in the three main geographical region of Peru. To test differences in proportions we used Chi2 or Fisher-exact tests. To test differences in means for continuous variables we used ANOVA or t-tests. Genetic ancestry was estimated using genome wide genotypes and the program ADMIXTURE. Tumor subtypes were defined using the following criteria: ER+/PR+/HER2- as luminal A, ER+/PR+/HER2+ as luminal B, ER-/PR-/HER2+ as HER2+ and ER-/PR-/HER2- as triple negative. Overall, the patients included in the study were relatively young (50 yrs, SD=11.0). The average number of full-term pregnancies was 3 (SD=1.8), the average age at first pregnancy 22 (SD=5.7) and age at menarche was 13 (SD=1.8). The tumor subtype distribution was 31% of Luminal B tumors, 24% luminal A, 12% HER2 and 12% triple negative and did not differ by place of birth or residence. We found that patients from the Coastal region were heavier and taller than those born in the Andean region (p<0.005). Women born in the Coastal region had the lowest age at menarche and a lower number of full-term pregnancies (p<0.0001). Similar trends were observed when we compared women by place of residence. Patients born in Lima, the Capital of Peru, smoke more (p<0.05), were heavier, had lower age at menarche, lower number of full term pregnancies and were diagnosed at a younger age, compared to women born outside the city (p<0.05). The distribution of NA genetic ancestry also varied by place of birth: patients born outside Lima had higher proportion of NA ancestry (78% SD=0.15 vs. 74%, SD=0.18, p<0.05). The distribution of tumor subtypes among women in the Peruvian breast cancer cohort did not differ by place of birth or residence. However, we found that for some breast cancer risk factors, exposures differed between women from different regions. Finally, given the relatively low observed values for reproductive and lifestyle related exposures and the high proportion of Indigenous American ancestry of Peruvian women, this cohort is likely to be particularly informative to study genetic predisposition to breast cancer. Citation Format: Valentina Zavala, Tatiana Vidaurre, Katie Marker, Jeannie Vásquez, L Tamayo, Renzo Florez, Sandro Casavilca, M Calderon, J Abugattas, H Gómez, H Fuentes, C Monge-Pimentel, S Song, D Cherry, Laura Fejerman. Tumor and risk factor characteristics among breast cancer patients from different geographic regions in Peru [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4184.

Molecular characteristics of breast cancer according to clinicopathological factors.

The purpose of the present study was to evaluate the correlation between molecular factors such as BRCA1 DNA repair associated (BRCA1), checkpoint kinase 2 (CHEK2) and nucleotide binding oligomerization domain containing 2 (NOD2) gene mutations and clinicopathological factors in patients with breast cancer (BC). Prognostic factors were analyzed in BC patients with confirmed BRCA1 (n=73), CHEK2 (n=51) and NOD2 (n=31) mutations. The control group was selected from BC patients without mutations (n=392). The BRCA-associated cancer cases were significantly more often triple negative compared with sporadic cancer (62% vs. 14%; P=0.0001). Luminal B HER2-positive and HER2-positive non-luminal subtypes were observed more often in the control group (33 and 17%). The luminal A subtype was detected in 53% of CHEK2 mutation carriers and 45% of NOD2 mutation carriers. A lower histological grade was observed significantly more often in patients with CHEK2 mutations in comparison with the control group (88 vs. 69%; P=0.003). Lymph nodes without metastases were reported more frequently in NOD2 mutation carriers (74 vs. 54%; P=0.038), in BRCA1 mutations (73 vs. 54%; P=0.004) and, although not significantly, in CHEK2 mutation carriers (69 vs. 54%; P=0.071) compared with the control group. In conclusion, BRCA1 mutation was associated with TNBC and the luminal B HER2 (-) subtype. HER2-positive subtypes were characteristic of the control group. CHEK2 and NOD2 mutation carriers had a more favorable profile of prognostic factors.