Proportion Of Breast Cancer Cases Research Articles

Precise subtyping reveals immune heterogeneity for hormone receptor-positive breast cancer

A significant proportion of breast cancer cases are characterized by hormone receptor positivity (HR+). Clinically, the heterogeneity of HR+ breast cancer leads to different therapeutic effects on endocrine. Therefore, definition of subgroups in HR+ breast cancer is important for effective treatment. Here, we have developed a CMBR method utilizing computational functional networks based on DNA methylation to identify conserved subgroups in HR+ breast cancer. Calculated by CMBR, HR+ breast cancer was divided into five subgroups, of which HR+/negative epidermal growth factor receptor-2 (Her2-) was divided into two subgroups, and HR+/positive epidermal growth factor receptor-2 (Her2+) was divided into three subgroups. These subgroups had heterogeneity in the immune microenvironment, tumor infiltrating lymphocyte patterns, somatic mutation patterns and drug sensitivity. Specifically, CMBR identified two subgroups with the “Hot” tumor phenotype. In addition, these conserved subgroups were broadly validated on external validation datasets. CMBR identified the molecular signature of HR+ breast cancer subgroups, providing valuable insights into personalized treatment strategies and management options.

Development of a CUB domain-containing protein 1 (CDCP1)-targeting antibody-drug conjugate for triple-negative and metastatic breast cancer.

e15012 Background: CUB-domain containing- protein 1 (CDCP1) is a transmembrane receptor involved in the progression of several cancers. Recent studies demonstrate that CDCP1 is a rational target for the development of innovative targeted therapies for cancer including theranostics agents and antibody-drug conjugates. Methods: To determine the therapeutic potential of CDCP1 in breast cancer, we investigated its expression in multiple cohorts of breast cancer tissues by immunohistochemistry, as well as in various preclinical models including cell lines, primary cells and patient-derived xenografts using flow cytometry, western blot and immunofluorescence staining. Then, we evaluated the capacity of the CDCP1-targeting chimeric antibody ch10D7 to specifically accumulate in breast cancer lesions in in vivo preclinical models including patient-derived xenografts and breast cancer metastasis models. Finally, we determined the efficacy of the ch10D7-MMAE antibody-drug conjugate to kill breast cancer cells in vitro and breast tumours ex-vivo and in vivo. Results: The CDCP1 receptor is expressed at targetable level in a significant proportion of breast cancer cases with high/intermediate expression detected in ~30% of localized ER-positive cases, ~50% of metastatic ER-positive cases and > 70% of Triple-negative or HER2-positive cases. Similar proportion of expression was detected in cellular models. We demonstrated that ch10D7 antibody labelled with the radionucleotide Zircodium-89 specifically accumulates in breast cancer lesions in vivo allowing the detection of mammary-fat pad implanted patient-derived xenografts and of breast cancer metastasis by PET/CT imaging. Finally, we confirmed that the ch10D7-MMAE antibody-drug conjugate is very efficient at inducing cell death in vitro as well as controlling primary tumour and metastatic tumour burden in pre-clinical models, conferring a significant survival advantage compared to classical therapy. Conclusions: Our work demonstrates that CDCP1 is a potential target to detect and limit the progression of breast tumours in both the primary and metastatic disease setting, particularly in triple-negative and HER2-positive breast cancer subtypes. Furthermore, we show that biomolecules specifically recognising this receptor are promising therapeutic agents which could improve survival of patients.

Abstract P4-07-26: Development of CDCP1-targeting antibody-drug conjugate for Triple negative and metastatic breast cancer

Abstract Introduction: CUB-domain containing- protein 1 (CDCP1) is a transmembrane receptor involved in the progression of several cancers. Recent studies demonstrate that CDCP1 is a rational target for the development of innovative targeted therapies for cancer including theranostics agents and antibody-drug conjugates. Objective/Methods: To determine the therapeutic potential of CDCP1 in breast cancer, we investigated its expression in multiple cohorts of breast cancer tissues by immunohistochemistry, as well as in various preclinical models including cell lines, primary cells and patient-derived xenografts using flow cytometry, western blot and immunofluorescence staining. Then, we evaluated the capacity of the CDCP1-targeting chimeric antibody ch10D7 to specifically accumulate in breast cancer lesions in in vivo preclinical models including patient-derived xenografts and breast cancer metastasis models. Finally, we determined the efficacy of the ch10D7-MMAE antibody-drug conjugate to kill breast cancer cells in vitro and breast tumours ex-vivo and in vivo. Results: The CDCP1 receptor is expressed at targetable level in a significant proportion of breast cancer cases with high/intermediate expression detected in ~30% of localized ER-positive cases, ~50% of metastatic ER-positive cases and >70% of Triple negative or HER2-positive cases. Similar proportion of expression was detected in cellular models. We demonstrated that ch10D7 antibody labelled with the radionucleotide Zircodium-89 specifically accumulates in breast cancer lesions in vivo allowing the detection of mammary-fat pad implanted patient-derived xenografts and of breast cancer metastasis by PET/CT imaging. Finally, we confirmed that the ch10D7-MMAE antibody-drug conjugate is very efficient at inducing cell death in vitro as well as controlling primary tumour and metastatic tumour burden in pre-clinical models, conferring a significant survival advantage compared to classical therapy. Conclusion: Our work demonstrates that CDCP1 is a potential target to detect and limit the progression of breast tumours and that biomolecules specifically recognising this receptor are promising agents which could improve survival of patients. Citation Format: Madeline Gough, Tashbib Khan, Kayden Kwah, Yaowu He, Gishan Ratnayake, Christopher Pyke, Cameron Snell, John Hooper, Thomas Kryza. Development of CDCP1-targeting antibody-drug conjugate for Triple negative and metastatic breast cancer [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 P4-07-26.

Breast cancer diagnostic delays in pakistan: a looming epidemic threat

Breast cancer is a major contributing factor to the mortality and morbidity burden among the female population in Asia. In 2020, a total of 1.2 million newly diagnosed breast cancer cases and an estimated 3.5 million deaths due to breast cancer were reported in Asia (International Agency for Research on Cancer, 2020a). In particular, Pakistan notably reported the highest proportion of breast cancer cases in Asia. Research estimates that one out of nine women in Pakistan is at a high risk of suffering from breast cancer in their lifetime. The constant growth in breast cancer rates in Pakistan indicates that breast cancer is rapidly reaching epidemic proportions and poses an urgent challenge to Pakistan's public health system. Due to system-level and patient-level delay factors, Pakistani women often seek medical care for breast carcinoma at an advanced stage of the disease, whereby survival chances are minimal. The key to mitigating the breast cancer burden in Pakistan is to foster early detection programs among Pakistani women. This review aims to examine the root causes of delayed detection of breast cancer in Pakistani women, emphasize the pivotal role of early detection in individuals' and populations' health promotion, and highlight nursing implications in promoting breast cancer early detection programs. A comprehensive literature search was conducted in databases including CINAHL, Google Scholar, and Scopus. The review consists of articles from 2005 to 2020 published in the English language only. Furthermore, the study also highlights the need for context-specific and culturally sensitive early breast cancer detection programs to potentially reduce barriers in the uptake of screening services among Pakistani women.

Risks and Function of Breast Cancer Susceptibility Alleles.

Simple SummaryPopulation-based genetic risk stratification and detection of early-stage breast cancers will improve approaches to prevent and reduce disease-associated mortalities. In this review, we summarize the latest discoveries in breast cancer susceptibility genetics and propose how these findings can be applied in the clinical arena to improve risk prediction and prevention of breast cancer. We also review the latest approaches and progress aimed at elucidating the functional consequences of both high and moderate penetrance genetic variation, which tend to lie in the protein coding regions of breast cancer susceptibility genes, and common low penetrance breast cancer risk alleles which tend to lie in non-protein coding DNA regions and affect gene regulation. For non-coding risk variation, there is no genetic code to interpret the function of common risk allele; and so, we provide the reader with an illustration of the step-by-step methods to understand their functional impact on breast cancer disease biology.Family history remains one of the strongest risk factors for breast cancer. It is well established that women with a first-degree relative affected by breast cancer are twice as likely to develop the disease themselves. Twins studies indicate that this is most likely due to shared genetics rather than shared epidemiological/lifestyle risk factors. Linkage and targeted sequencing studies have shown that rare high- and moderate-penetrance germline variants in genes involved in the DNA damage response (DDR) including BRCA1, BRCA2, PALB2, ATM, and TP53 are responsible for a proportion of breast cancer cases. However, breast cancer is a heterogeneous disease, and there is now strong evidence that different risk alleles can predispose to different subtypes of breast cancer. Here, we review the associations between the different genes and subtype-specificity of breast cancer based on the most comprehensive genetic studies published. Genome-wide association studies (GWAS) have also been used to identify an additional hereditary component of breast cancer, and have identified hundreds of common, low-penetrance susceptibility alleles. The combination of these low penetrance risk variants, summed as a polygenic risk score (PRS), can identify individuals across the spectrum of disease risk. However, there remains a substantial bottleneck between the discovery of GWAS-risk variants and their contribution to tumorigenesis mainly because the majority of these variants map to the non-protein coding genome. A range of functional genomic approaches are needed to identify the causal risk variants and target susceptibility genes and establish their underlying role in disease biology. We discuss how the application of these multidisciplinary approaches to understand genetic risk for breast cancer can be used to identify individuals in the population that may benefit from clinical interventions including screening for early detection and prevention, and treatment strategies to reduce breast cancer-related mortalities.

DNA-based screening and population health: a points to consider statement for programs and sponsoring organizations from the American College of Medical Genetics and Genomics (ACMG)

DNA-based screening and population health: a points to consider statement for programs and sponsoring organizations from the American College of Medical Genetics and Genomics (ACMG)

Preventive measures against development of breast cancer

According to Russian statistics, breast cancer ranks fi rst among malignant neoplasms among women (20.9%). The largest proportion of breast cancer cases is detected in women aged 35 to 55 years. Therefore, an urgent issue is not only the provision of specialized medical care to patients, but also the prevention of the development of the disease. Almost 70% of malignant neoplasms, including breast cancer, are provoked by exogenous factors. This article provides an overview of the literature on primary breast cancer prevention. It is established that a woman's lifestyle, diet, physical activity, and bad habits can have a potentiating effect on the development of breast cancer. Conclusions. Currently, breast cancer prevention plays a key role in the fi ght against this disease. middle-aged women (who account for the main peak of morbidity) should understand that by changing behavior, it is possible to reduce the risk of developing breast cancer. In addition, increasing women's awareness of breast cancer and its prevention can help reduce the incidence and fi nancial costs of treatment.

D-1 / PD-L1 EXPRESSION IN INVASIVE BREAST CARCINOMA / CANCER

Objective: To investigate the immunohistochemical expression of PD-1 and PD-L1 in breast cancer cases and itscorrelation with clinicopathological factors.
 Study Design: Cross sectional study.
 Place and Duration of Study: Histopathology department, Armed Forces Institute of Pathology Rawalpindi, form Jan to Jun 2019.
 Methodology: Sixty five cases of breast cancer were retrieved. Clinicopathological parameters like age, gender,tumor grade and receptor status were noted. Immunohistochemistry for PD-1 and PD-L1 was applied. The datawas entered and statistical analysis was done using SPSS version 21. The associations between variables werefound using the Fisher exact test.
 Results: Sixty five cases of breast cancer were investigated from tumour registry. The sample included femalepatients, having mean age of 50.86 ± 11.1 Years. Invasive mammary (ductal) carcinoma, NST was the most prevalent subtype 60 (92.3%) and most tumors were grade I/II 53(82%). PD-1 expression was seen in TIL’s 31 (48%) and PD-L1 expression was observed in tumour cells 30 (46%). Expression of PD-1/PD-L1 expression was more common in premenopausal age group and grade I/II tumors. Among molecular subtypes, PD-L1 expression was detected in 11 (52%) TNBC, 5 (71%) in HR-/HER2+ and 12 (32)% in HR + HER2 - and PD-1 expression was observed in 13 (62%) TNBC, 5 (71%) in HR-/HER2+ and 13 (35%) in HR+ HER2-.
 Conclusion: A large proportion of breast cancer cases show expression of PD-1 / PD-L1. Anti PD-1 and PD-L1therapy may benefit these patients.

DTX3 copy number increase in breast cancer: a study of associations to molecular subtype, proliferation and prognosis

PurposeThe degree of cell proliferation is important for subclassification of breast cancers into prognostic and therapeutic groups. DTX3 has been identified as a driver of proliferation in luminal breast cancer. In this study, we describe DTX3 copy number in breast cancer primary tumours and corresponding axillary lymph node metastases, and studied associations with molecular subtype, proliferation and prognosis.MethodsUsing fluorescence in situ hybridization, we assessed DTX3 and chromosome 12 centromere (CEP12) copy number in 542 primary breast cancers and 117 lymph node metastases, from a well-described cohort of Norwegian breast cancer patients. Proliferation was expressed as mitotic counts and Ki67 score. Associations between DTX3 copy number and molecular subtype and proliferation were assessed using Pearson’s χ2 test. We studied the effect of copy number increase on prognosis estimating cumulative incidence of breast cancer death and hazard ratios.ResultsMean DTX3 copy number ≥ 4 was found in 23 tumours (4%), and mean ≥ 5 in 9 tumours (1.7%). Copy number increase was found within all molecular subtypes except the 5 negative phenotype and the Luminal B (HER2 +) subtype. DTX3 copy number increase was not accompanied by an increase in CEP12. Point estimates showed that there were associations between DTX3 copy number increase and high proliferation and poor prognosis; however, precision depended on copy number cut-off.ConclusionsDTX3 copy number increase was present in a small proportion of breast cancer cases. There was an association between copy number increase and high tumour cell proliferation and poor prognosis.

BRCA1 and BRCA2 genes mutations among women with clinical signs of hereditary breast cancer in western Belarus

Background: Breast cancer is the most common malignancy in women. In the countries of Central and Eastern Europe founder mutations in the BRCA1 and BRCA2 genes are responsible for a significant proportion of breast cancer cases; however, regional differences in the frequencies of various mutations may occur. The spectrum and frequency of BRCA1 and BRCA2 mutations among breast cancer patients have not yet been fully explored in Belarus. Aim: In this study, we aimed to estimate the incidence of BRCA1 and BRCA2 causative founder variants in breast cancer female patients with clinical signs of hereditary disease in western Belarus. Materials and Methods: Blood samples from 71 breast cancer female patients with clinical signs of hereditary disease from the western region of Belarus were examined. We studied 13 causative founder variants in BRCA1 (c.5266dupC, c.4035delA, c.5251C>T, c.181T>G, c.676delT, c.68_69delAG, c.3770_3771delAG, c.1687C>T, c.3756_3759delGTCT) and BRCA2 (c.658_659delGT, c.7910_7914delCCTTT, c.3847_3848delGT, c.5946delT) genes characteristic for the population of Central Europe. The study included 22 female patients with early-onset form, 8 individuals with bilateral and 41 women with multiple primary breast cancer. Results: 32 out of 71 patients (45 %) had one of the causative founder variants in the BRCA1 and BRCA2 genes. The most common mutation defined in these genes was BRCA1 c.5266dupC; it was detected in 19 women with breast cancer (27 %). The carrier of the pathogenic BRCA1 allele c.4035delA was confirmed in 8 cases (11 %). BRCA1 gene mutations were found to be significantly more common in presence of two or more signs of genetic predisposition to breast cancer. However, among 50 patients with a family medical history of breast and/or ovarian cancer and clinical signs of hereditary cancer, mutations in the BRCA1 and BRCA2 genes were found only in 24 (48 %) cases. Conclusion: The study showed high incidence of germinal BRCA1 mutations (45 %) among breast cancer patients in the western region of Belarus. Only two BRCA1 mutations (c.5266dupC, c.4035delA) are detectable in approximately 84 % of carriers. It is necessary to continue studying the mutations in the genes associated with development of breast cancer that are typical for Belarusian population, especially in the group of young female patients, since this study has confirmed the genetic predisposition only in every third patient under the age of 50.

Outcome of adjuvant chemotherapy in elderly patients with early-stage, hormone receptor-positive, HER-2-negative breast cancer.

The proportion of breast cancer cases among elderly (over 70years old) patients is expected to rise from 24% to 35% by the next decade. However, elderly patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER-2)-negative, node-negative breast cancer were underrepresented in prior landmark prospective trials. Using a nationwide hospital cancer registry, our study of 12004 elderly patients demonstrates that adjuvant chemotherapy was not associated with overall survival (hazards ratio [HR] 0.96, 95% confidence interval [CI] 0.77-1.20, P=.71). Given the toxicities associated with systemic treatment, cautious recommendation or the omission of chemotherapy may be considered in select elderly patients.

Adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Recommendations and Breast Cancer in the SUN Project.

A proportion of breast cancer cases are attributable to combined modifiable risk factors. The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) has recently updated the recommendations for cancer prevention and a standard scoring system has been published. The aim of this study was to evaluate the association between compliance with the 2018 WCRF/AICR cancer prevention recommendations (Third Expert Report) and the risk of breast cancer in the SUN (“Seguimiento Universidad de Navarra”) prospective cohort. Spanish female university graduates, initially free of breast cancer, were included (n = 10,930). An 8-item score to measure compliance to the recommendations was built: body fat, physical activity, consumption of wholegrains/vegetables/fruit/beans, “fast foods”, red/processed meat consumption, sugar-sweetened drinks consumption, alcohol intake, and breastfeeding. A stratified analysis was conducted according to menopausal status. A non-significant inverse association was observed for overall breast cancer. The inverse association became statistically significant for post-menopausal breast cancer after multivariable adjustment (hazard ratio for > 5 vs. ≤ 3 points = 0.27; 95% CI: 0.08-0.93). The results suggested that the possible inverse association with breast cancer was attributable to the combined effects of the different nutritional and lifestyle components.

Investigation of triple negative breast cancer rates in women diagnosed with breast cancer in Trinidad and Tobago.

e19005 Background: According to the WHO/PAHO, Trinidad and Tobago (T&T) has the 2nd highest breast cancer mortality rate in the Caribbean region. In T&T, citizens of African descent make up about 36.8% of the T&T population, with 24.8% being of East Indian ancestry, and 32.4% identifying as having mixed heritage. In the United States, it has been showed that African American women, despite being diagnosed less often, have an earlier onset of breast cancer with less favorable clinical outcomes. One of the factors studied has been the higher frequency of triple negative breast cancer (TNBC) in African American women particularly when these patients are diagnosed at a younger age. Notably, a large proportion of breast cancer cases in T&T appear to occur at a young age, with nearly 36% of them being diagnosed under the age of 50. However, breast cancer tumor phenotypes have not been well studied. Therefore, we sought to investigate the distribution of tumor hormone receptor markers in the T&T breast cancer population. Methods: At the National Radiotherapy Center, T&T’s main oncology unit, we investigated breast cancer patients born in T&T using paper chart reviews. We collected information about their demographics, personal breast cancer diagnosis, tumor hormone receptor status and germline genetic testing results. Results: So far, we reviewed 90 patient charts, and in our sample, 33.3% (30/90) had TNBC. This is higher than the rates in the US where TNBC accounts for 10-20% of breast cancer patients, and of those TNBC cases, 10.6% have BRCA 1 or BRCA 2 mutations. In our T&T sample, of those with TNBC, 23.3% (7/30) had a HBOC mutation (5 BRCA, 1 TP53 and 1 PTEN). Average diagnosis age of TNBC cases reported in our sample was 45.7 years. In our sample, 52.2% (47/90) identified as having African ancestry, 37.8% (34/90) identified as having East Indian ancestry and 10% (9/90) identified as Mixed. Of the patients with TNBC, 63.3% (19/30) were of African ancestry, 30.0% (9/30) were of East Indian ancestry and 6.7% (2/30) identified as Mixed. Conclusions: Therefore, our sample results suggest that there is a significant portion of the breast cancer cases being TNBC in the T&T population, particularly in citizens with African ancestry. As we continue to finalize the incoming data, we hope to draw associations between tumor pathology, clinical presentation and genetic profiles. However, these initial results demonstrate the need to study tumor pathology within the T&T population, as this could lead to improved clinical and screening guidelines specific to T&T citizens.

Expression of Tumour-Associated MUC1 Is a Poor Prognostic Marker in Breast Cancer in Kumasi, Ghana.

Background Immunohistochemical assessment of breast cancer and stratification into the basic molecular subtypes afford a much deeper insight into the biology of breast cancer, while presenting with opportunities to exploit personalized, targeted treatment. Traditionally, the oestrogen, progesterone, and epidermal growth factor receptors are assessed. MUC1, a transmembrane mucin, has been demonstrated a potential prognostic and metastatic marker in breast cancer. However, there have been a limited number of studies addressing the predictive and prognostic features of MUC1 in African breast cancer. This study aims at addressing the expression profiles of MUC1 and other biomarkers in Ghanaian breast cancer and determines its predictive and prognostic characteristics, in relation to other clinicopathological features. Methods Haematoxylin and eosin (H&E) slides of breast cancer cases were reviewed and 203 suitable cases were selected for tissue microarray (TMA) construction and immunohistochemistry. Anti-ER, PR, HER2, Ki-67, and MUC1 antibodies were used. Results from the immunostaining were analysed using SPSS version 23. Results About 59% of cases expressed MUC1. Majority of cases in the study showed a lack of expression of all three traditional markers (29% expressed ER, 10.9% PR, and 20.7% HER2). Ki-67 index were 62.1% (low), 16.5% (moderate), and 21.4% (high). MUC1 expressions among the molecular classes were luminal A (60.7%), luminal B (68.8%), HER2 overexpression (87.5%), and triple negative (56.6%). There were significant associations between MUC1 and HER2 overexpression (p=0.01) and triple negative (p < 0.01). Conclusion The high proportion of breast cancer cases expressing MUC1, as well as its association with the two most aggressive molecular classes, indicate a substantial role in the biology of breast cancer in our cohort, and it is an indication of poor prognosis.

Abstract P1-10-16: Ethnicity, recurrence score (RS) distribution, and clinical outcomes in ER+ HER2-negative breast cancer (BC) patients (pts) in Israel

Abstract Background: The RS assay is widely used in ER+ HER2-negative BC to guide treatment decisions. In TAILORx, RS distribution was similar in blacks vs whites and in Hispanics vs non-Hispanics. Also, TAILORx analyses revealed similar results across ethnic groups with endocrine therapy being consistently noninferior to chemotherapy (CT) plus endocrine therapy in RS 11-25 pts. We investigated RS distribution among Jewish vs Arab/Druze pts who underwent RS testing through Clalit Health Services (CHS), the largest HMO in Israel, as well as differences in CT use and clinical outcomes between these 2 ethnic groups. Methods: The RS distribution analysis included all CHS pts (regardless of nodal status) who were tested between 1/2006 and 2/2019. For the clinical outcomes analysis, we employed a dataset used in prior analyses (Stemmer et al, poster# 249, SG-BCC 2019) of node-negative pts who were tested between 1/2006 and 12/2009, and as such, it is a subset of the cohort used for the RS distribution analysis. The study was approved by the IRB of the CHS Community Division and was granted a waiver for obtaining pt consent. Results: The RS distribution analysis involved 9054 pts who were tested in the evaluated timeframe and for whom RS results and ethnicity information were available. These included 8223 (91%) Jews and 831 (9%) Arabs/Druze, approximately reflecting the proportion of BC cases diagnosed in the respective ethnic groups. The 2 groups were similar in their baseline pt/tumor characteristics except for age and tumor size (Table). RS distribution was also similar between the 2 ethnic groups (Table). The subset of node-negative pts for whom treatment and clinical outcomes are known included 1274 (93%) Jewish pts and 91 (7%) Arab/Druze pts. In this subset, the only statistically significant difference in pt/tumor characteristics between the ethnic groups was age (median [interquartile range]) of 60 [53-66] yrs in the Jewish pts vs 55 [48-63] yrs in the Arab/Druze pts; P=.0004), similar to the complete cohort. The RS distribution was similar to that in the larger cohort, with no significant differences between the ethnic groups (P=.75). Also, CT use was consistent with the RS result in both ethnic groups, and was overall somewhat higher among Arab/Druze pts (25% vs 19%), due primarily to higher CT use among Arabs/Druze pts in the largest RS category (11-25), in which significant differences with respect to age were noted (median [interquartile range], 59 [52-66] yrs in Jewish pts vs 52 [46-61] yrs in Arab/Druze pts; P&amp;lt;.0001). CT use was 0%, 9%, and 69% in Jewish pts with RS 0-10, 11-25, and 26-100, respectively, whereas in Arab/Druze pts, the respective CT use was 0%, 14%, and 75%. At 10 years, clinical outcomes (all RS groups combined) were similar in the ethnic groups; 10-year breast cancer-specific mortality was 3.7% (95% CI, 2.6-5.3%) for Jewish pts and 4.4% (95% CI, 1.4-13.2%) for Arab/Druze pts. Conclusions: RS distribution and clinical outcomes were similar in Jewish and Arab/Druze BC pts. Arab/Druze pts undergoing RS testing were overall younger than the Jewish pts, which may suggest under-diagnosis and/or under-testing in the older Arab/Druze pt population. Also, CT use seemed higher in the Arab/Druze pt population, possibly reflecting the differences in the age distribution between these ethnic groups. Table: Patient/tumor characteristics by ethnicityJewsArabs/DruzeP valuen = 8223n = 831Female, n (%)8132 (98.9%)825 (99.3%).3Median (interquartile range) age, years62 (53-68)55 (48-64)&amp;lt;.0001Nodal status, n (%).14Node-negative5974 (72.6%)583 (70.2%)N1mi552 (6.7%)52 (6.3%)1-3 positive nodes1506 (18.3%)180 (21.7%)≥4 positive nodes18 (0.2%)2 (0.2%)Unknown173 (2.1%)14 (1.7%)Median (interquartile range) tumor size in the greatest dimension, cm2.0 (1.2-2.2)1.8 (1.4-2.5)&amp;lt;.0001Tumor size category, n (%)&amp;lt;.0001≤1 cm1714 (20.8%)112 (13.5%)&amp;gt;1 - 2 cm4233 (51.5%)411 (49.5%)&amp;gt;22153 (26.2%)302 (36.3%)Unknown123 (1.5%)6 (0.7%)Tumor grade category, n (%).12Grade 11109 (13.4%)123 (14.8%)Grade 24192 (51.0%)443 (53.3%)Grade 31389 (16.9%)120 (14.4%)Not applicable/Unknown1533 (18.6%)145 (17.4%)Histology, n (%).92IDC6530 (79.4%)665 (80.0%)ILC1113 (13.5%)113 (13.6%)Papillary79 (1.0%)10 (1.2%)Mucinous/colloid144 (1.8%)16 (1.9%)Other/unknown357 (4.3%)27 (3.2%)Recurrence Score category, n (%).170-101612 (19.6%)176 (21.2%)11-255091 (61.9%)522 (62.8%)26-1001520 (18.5%)133 (16.0%) Citation Format: Gil Bar Sela, Yousef Samih, Rinat Yerushalmi, Michelle Leviov, Noa Efrat Ben-Baruch, Iryna Kuchuk, Margarita Tokar, Tamar Peretz, Amir L Sonnenblick, Lior Soussan-Gutman, Avital Bareket-Samish, Georgeta Fried, Shani Paluch-Shimon, Bella Kaufman, Ariel Hammerman, Nicky Liebermann, Salomon M Stemmer. Ethnicity, recurrence score (RS) distribution, and clinical outcomes in ER+ HER2-negative breast cancer (BC) patients (pts) in Israel [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-16.

Role of androgen and microRNA in triple-negative breast cancer.

Breast cancer (BC) is the most frequent type of malignancy affecting females worldwide. Molecular-based studies resulted in an identification of at least four subtypes of breast carcinoma, including luminal A and luminal B, Human growth factor receptor (HER-2)-enriched and triple-negative tumors (basal-like and normal breast-like). A proportion of BC cases are of the triple-negative breast cancer (TNBC) type. TNBC lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and HER-2, and is known to express androgen receptor (AR) at considerable levels. AR has been shown to promote the progression of TNBC. However, the exact mechanisms have yet to be unraveled. One of these mechanisms could be through regulating the expression of microRNA (miRNA) molecules, which play an important regulatory role in BC through post-transcriptional gene silencing. Activation of AR controls the expression of miRNA molecules, which target selective mRNAs, consequently, affecting protein expression. In this review we attempt to elucidate the relations between AR and miRNA in TNBC.

Breast Cancer Incidence and Behavior in Younger Patients: A Study From the Surveillance, Epidemiology and End Results Database.

BackgroundBreast cancer screening for women less than 40 years old is practically non-existent. Since screening can detect cancer at an early stage, not having a surveillance guideline for breast cancer in younger women can result in detection of the cancer at advanced stages. The purpose of this study was to investigate the incidence and behavior of breast cancer in younger women.MethodsThe Surveillance, Epidemiology and End Results (SEER) registry data from 2004 to 2014 were accessed for the study. All women diagnosed with breast cancer and with complete information were included in the study. The data were further divided into two groups based on the age of the patient at the time of diagnosis. The younger group consisted of women < 40 years old (group 1) and the older group consisted of women ≥ 40 years old (group 2). Both groups were compared on demography and characteristics of the cancer. The continuous variables were tested using Student’s t-tests and categorical variables were compared using Chi-squared or Fisher’s exact tests. Multivariate analysis was done to find the association of high-grade cancer using a logistic regression model. All P-values are two-sided and values < 0.05 were considered statistically significant.ResultsOf 599,782 patients who satisfied the inclusion criteria, 28,243 (4.71%) diagnosed with breast cancer were younger women aged < 40 years old. A higher proportion of these younger women presented with larger tumor sizes (between 5.1 and 10.0 cm) (11.61% vs. 5.70%, P < 0.001), poorly differentiated cancer cells (55.88% vs. 32.85%, P < 0.001) and triple negative receptors (6.83% vs. 3.81%, P < 0.001) than older women respectively. Younger age was significantly associated with high-grade tumor at presentation when controlling for race and marital status. There was roughly 3% increased risk of a high-grade tumor with each decrease of 1 year (odds ratio 0.97, 95% confidence interval 0.96 - 0.99, P = 0.001).ConclusionThis study found that the proportion of breast cancer cases in younger women was just below 5%; however, when the cancer was diagnosed, these women presented in advanced stages and more aggressive cancer types.

Investigation of HBOC germline mutations in women diagnosed with breast cancer in Trinidad and Tobago.

6574 Background: Trinidad and Tobago (T&amp;T) is the southern-most Caribbean island, and according to the WHO/PAHO, it has the 2nd highest breast cancer mortality rate in the region. Notably, a large proportion of breast cancer cases in T&amp;T occur at a young age; with nearly 36% of them being diagnosed under the age of 50. There is a known association between a younger age at diagnosis and Hereditary Breast and Ovarian Cancer syndrome (HBOC). Yet, the prevalence of HBOC mutations remains unknown in T&amp;T, as genetic counseling and testing services are extremely limited in the region. Therefore, we sought to determine the prevalence and spectrum of HBOC mutations in T&amp;T. Methods: At the National Radiotherapy Center, T&amp;T’s main oncology unit, female breast cancer patients, who met NCCN criteria for further genetic counseling and testing were recruited through chart reviews. After pre-test counseling, enrolled subjects had a detailed interview about their personal breast cancer diagnosis and family history. A saliva sample was collected using an Oragene kit, and analyzed by Color Genomics Inc. for 30 genes associated with hereditary cancers. Finalized results were returned to patients by genetic counselors from Color Genomics. Results: A total of 118 female patients who met NCCN guidelines for HBOC testing received genetic testing. A majority were 50 years of age or younger (69/118, 59%). The cohort was ethnically diverse: 34% African, 15% Asian, 48% multiple ethnicity, and 3% other/unknown. A pathogenic or likely pathogenic variant (positive result) was identified in 21.2% of the cohort (25/118) - most commonly identified in the BRCA1 gene (13/25, 52%), followed by BRCA2 (5/25, 20%), PTEN (2/25, 8%), BRIP1 (1/25, 4%), CHEK2 (1/25, 4%), MSH6 (1/25, 4%), PALB2 (1/25, 4%), and RAD51C (1/25, 4%). Conclusions: We found a strikingly high HBOC germline mutation prevalence rate of 21.2% among a cohort of female breast cancer patients meeting NCCN criteria for HBOC testing in T&amp;T. Given the growing implications of germline HBOC mutations for breast cancer treatment and prevention, our results demonstrate an urgent need for funding, as well as the development of robust genetic counseling and testing services in T&amp;T.

Modelling the role of dual specificity phosphatases in herceptin resistant breast cancer cell lines

BackgroundBreast cancer remains the most lethal type of cancer for women. A significant proportion of breast cancer cases are characterised by overexpression of the human epidermal growth factor receptor 2 protein (HER2). These cancers are commonly treated by Herceptin (Trastuzumab), but resistance to drug treatment frequently develops in tumour cells. Dual-specificity phosphatases (DUSPs) are thought to play a role in the mechanism of resistance, since some of them were reported to be overexpressed in tumours resistant to Herceptin. ResultsWe used a systems biology approach to investigate how DUSP overexpression could favour cell proliferation and to predict how this mechanism could be reversed by targeted inhibition of selected DUSPs. We measured the expression of 20 DUSP genes in two breast cancer cell lines following long-term (6 months) exposure to Herceptin, after confirming that these cells had become resistant to the drug. We constructed several Boolean models including specific substrates of each DUSP, and showed that our models correctly account for resistance when overexpressed DUSPs were kept activated. We then simulated inhibition of both individual and combinations of DUSPs, and determined conditions under which the resistance could be reversed. ConclusionsThese results show how a combination of experimental analysis and modelling help to understand cell survival mechanisms in breast cancer tumours, and crucially enable us to generate testable predictions potentially leading to new treatments of resistant tumours.

Patient Characteristics and Predictors of Advanced Breast Cancer Stage at a Public Referral Hospital in a Middle-Income Sub-Saharan African Country

Background: Breast cancer is the second leading cause of death in women in Botswana, a middle-income country in sub-Saharan Africa where cancer treatment is free to all citizens. While treatment is accessible, treatment outcomes may be limited by delayed diagnosis and or suboptimal treatment. Aim: As a preliminary step to understanding ways to improve early diagnosis of breast cancer in Botswana, we aimed to describe sociodemographic and clinical characteristics of breast cancer patients receiving specialized oncology care. Methods: Retrospective review of electronic data of patients enrolled in Thabatse Cancer Cohort study, including female patients diagnosed with breast cancer between October 2010 and July 2017 was conducted. Patient sociodemographic and clinical characteristics were described. We used univariate and multivariable logistic regression to explore predictors of advanced stage (III or IV) at presentation. Patients without known cancer stage were excluded. All factors significant in univariate analysis ( P &lt; 0.05) were included in final multivariable model. Statistical analyses were performed using R on an EZR platform. Results: A total of 481 female breast cancer patients were included in our analysis, with median age of 52.4 (IQR 44.0- 64.4) years. Majority of patients were not married (61%), nearly half (48%) had primary school or less education, 54% had income of less than $50 per month, and 30% were HIV positive. Overall, 260 (54%) were diagnosed with advanced cancer stage, 144 (30%) had early-stage cancer, and 77 (16%) had unknown cancer stage. Compared with early-stage cancer; income of less than $50 per month (odds ratio [OR] 1.58, 95% CI 1.03-2.44) and not having an indoor toilet (OR 0.56, 95% CI 0.36-0.87) were significantly associated with advanced cancer. Importantly, no significant association was detected for HIV infection (OR 1.29, 95% CI 0.79-2.13), education (OR 1.19, 95% CI 0.77-1.83) and electricity at home (OR 0.97, 95% CI 0.56-1.64). In the adjusted model only income of less than $50 per month was significantly associated with advanced cancer (adjusted OR 1.85, 95% CI 1.17-2.93). Conclusion: Our findings indicate that a high proportion of breast cancer cases receiving specialized oncology care were diagnosed at an advanced stage. While patients from lower socioeconomic seem to be at higher risk, these data suggest that broad sectorial interventions are needed to reduce cancer stage at presentation rather than targeted programs focused on individual populations or barriers.