bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous expression of androgen receptor and tumor-associated neutrophil in breast cancer subtypes.
Authors: Moghimi Minoosh , Vadoudi Shahin , Amirian Majid , Ahmadi Farzane , Amirian Mohammad Borna , Khodadadi Kasra , Mansouri Reza 
Published: June 2023

e12539 Background: Considering the heterogeneity of breast cancer phenotypes and different response rates to treatment, it is essential to determine prognostic markers that could confer therapeutic role as well. In this study, androgen receptor (AR) and tumor-associated neutrophil (TAN) in female breast cancer were investigated and their coherency with different subtypes of breastcancer and pathology findings were assessed. Methods: This cross-sectional study was conducted on patients with Stage I-IV breast cancer who were referred to Borna Pathology Center in Zanjan, Iran during 2018-2021. The tumoral paraffine blocks were evaluated for AR (by the IHC method) and TAN (by morphology and the IHC staining for myeloperoxidase). Relationships in different subtypes and stages were assessed.Using univariate logistic regression between 5 subtypes (defended by ER, PR, HER2, and Ki67), stage, age, metastasis (M), and grade with AR and TAN were studied separately and simultaneously. Results: We collected data from 83 women with Stage I-IV breast cancer with mean ± SD age of diagnosis 49.3±11.2 years. Percentage of AR+, TAN+, and AR+&TAN+ were 71.1, 43.4, and26.5, respectively. The frequency of AR+ and AR-&TAN- was high in hormone-positive subtypes, while TAN+ was frequent in the triple-negative group and AR+&TAN+ in Luminal A and B groups. The relation between age, M, and Stage with AR, TAN, and AR & TAN was not significant. AR was significantly related to subtype and grade. Conclusions: AR+ probability was significantly lower in Triple Negative subtype and poorly differentiated grade. Based on the heterogeneity of the presentation of these markers, survival evaluation can be important in risk assessment of them. Relationship between AR, TAN, and AR&TAN with study variables. [Table: see text]
Neutrophil/lymphocyte ratio (NLR) and albumin-globulin ratio (AGR): Correlations with outcomes in patients with stage I-III breast cancer.
Authors: Tey Min Li , Zhou Siqin , Nitar Phyu , Mohd Ishak Hanis Mariyah , Yang Christina Shi-Hui , Kusumawidjaja Grace , Chay Wen Yee , Wong Fuh-Yong , Wong Ru Xin 
Published: June 2023

e12548 Background: The ratios of blood-based inflammatory biomarkers, such as NLR and AGR, have been found to correlate with outcomes in various malignancies. Higher NLR values reflect a pro-inflammatory state and are generally associated with worse outcomes. Conversely, higher AGR values reflect a fitter nutritional status and/or less chronic inflammation, and may hence be associated with better outcomes. We aim to investigate the association between NLR and AGR with survival among stage I-III breast cancer patients treated curatively, and with pathological complete response (pCR) rates among patients who have undergone neoadjuvant chemotherapy (NACT). Methods: A retrospective study of stage I-III breast cancer patients treated in a healthcare cluster in Singapore from 2011-2017 was performed. Clinical data was extracted from a prospectively maintained registry alongside full blood count (FBC) and liver function test (LFT) results. FBC and LFT were performed either 1-month pre-chemotherapy or pre-operatively. pCR is defined as stage ypT0/isN0M0 among patients who have undergone NACT. Optimal cut-offs for the NLR and AGR values are determined by maximal Youden’s Index for pCR, DFS and OS. Multivariate logistic regression, with NLR, AGR, age, stage, grade, and subtype, was used, with survival data between groups compared using the Cox regression analysis and log-rank tests. Results: A total of 1,188 patients were included in our study, with 323 patients receiving NACT, and 865 patients undergoing upfront surgery. On multivariable analysis of patients treated with NACT, higher AGR was associated with higher pCR (cutoff >1.3, HR 2.0, p=0.02) and better DFS (>1.6, HR 0.4, p=0.02) while a higher NLR with worse DFS (>4.1, HR 1.8, p=0.03). In upfront surgery patients, higher AGR was associated with better OS (cutoff >1.2, HR 0.5, p=0.00) while a higher NLR predicted for worse OS (>2.4, HR 1.6, p=0.02). Conclusions: Inflammatory markers may be useful in predicting response to NACT and prognosticating survival. Larger studies should be undertaken to explore their value in clinical decision making. [Table: see text]
Correlation between Magee score and recurrence score in Indian patients with breast cancer.
Authors: Davis Sissmol , John Dr Serene Sara , Santoki Aditya , Sankaranarayanan Sreedharan , Keechilat Pavithran , Thampy Cherian , Shivashankara Yashaswini , Thomas Boben , Baghmar Saphalta , Rajendranath Rejiv , Warrier Narayanankutty Edavalath , Mathew Aju 
Published: June 2023

e12555 Background: Recurrence score (RS) from Oncotype Dx (ODx) test predict chemotherapy benefit in estrogen receptor (ER) positive, and HER2-negative patients with breast cancer. ODx is an expensive test in an Indian practice setting - cost of adjuvant chemotherapy is one-sixth of the cost of the test. Magee equations use histopathological variables, and semiquantitative results from ER, PR and Ki-67, to calculate Magee score (MS) and provide a cost-effective surrogate mechanism for predicting RS. We aimed to assess the correlation between MS and RS in an Indian setting. Methods: Pathology reports were obtained from oncologists in India. Immunohistochemistry for ER and PR were reported using the Allred system. Therefore, two methods were identified to estimate H-scores - using a calculated method (A), and using an expert-approximated (B) method. MS were calculated by a single investigator blinded to the RS. MS and RS were then assessed for correlation via the Pearson correlation method. MS were arbitrarily stratified into ≤ 15, 15 - 30, and ≥ 30, and their overall agreement (OA) or concordance with RS risk categories, ≤ 15, 15 - 30, and ≥ 30, were assessed. The OA was assessed by determining the proportion of patients in similar risk categories across low, intermediate and high-risk RS and MS. Results: Among 34 patients included in the study, 38% (13) had an RS ≤ 15, 38% (13) had an RS between 15 and 30, and 23% (8) had an RS ≥ 30. Correlation coefficient between MS and RS was 0.78 for both methods of estimation (p<0.0001). The OA between MS-A and RS, and MS-B and RS were 59% (20/34) and 47% (16/34) respectively. The concordance between low-risk MS-A and RS is 78% (n=9) and between low-risk MS-B and RS is 50% (n=20). The concordance between high-risk MS-A and RS is 100% (n=2) and high-risk MS-B and RS is 100% (n=2). Conclusions: Although there is good correlation between RS and MS, the concordance between the two in similar risk categories is not optimal. Of the two methods to estimate H-score from Allred score, the calculated method seems to be more optimal. Our pilot study shows good correlation between MS and RS. We recommend that pathologists incorporate H-score as part of the reporting of ER and PR. A larger prospective study will be useful to test our hypothesis for the use of MS as a predictive tool for adjuvant chemotherapy in breast cancer.
Use of the genetic signature of 70-genes MammaPrint in comparision with the immunohistochemical profile to de-escalate systemic treatment in the elderly population: Real-world study (AGEMA-BR).
Authors: Mansani Fabio , Freitas-Junior Ruffo 
Published: June 2023

e12561 Background: the elderly population, generally, presents a lower performance and greater susceptibility to complications and adverse effects of therapies, inferring that the de-escalation of cytotoxic therapies is desirable. Genetic signatures, including MammaPrint/ BluePrint, are the most appropriate tools to select among estrogen receptor (ER) patients with high clinical risk, who could, with oncological safety, not receiving adjuvant chemotherapy. Objective – to evaluate the performance of MammaPrint™ (MP) / BluePrint (BP) and the immunohistochemical profile (IHC) in the de-escalation of systemic therapy in the elderly population with breast cancer and Luminal profile. Methods: from the patients in the AGEMA-BRA study, which analyzes the performance of the 70-gene MammaPrint™ platform in the Brazilian population, those aged 70 years or older, with high clinical risk, who had data on the immunohistochemical profile available (37 patients). A comparative analysis was performed between the genomic profile (Luminal A/B on BluePrint; high and low risk on MammaPrint™ and the immunohistochemical profile (considered Luminal A with ER >10%, RP>10%, HER2 negative, Ki67 ≤20% Luminal B with ER>10%, HER2 negative, Ki67>20%) and clinical endpoints including disease-free survival (DFS) and overall survival (OS). Data analysis used accuracy and the Kappa coefficient (considering concordance >0, 6). Results: mean age at diagnosis 73.1 years (70–80 years) and mean follow-up (FU) of 42 months. Of the 15 patients with high risk / luminal B by MP / BP, 5 were classified as luminal A by the IHC profile with a disagreement of 33.33%; of the 22 low-risk / luminal A patients by MP/BP, 6 were classified as luminal B by the IHC, a disagreement of 27.27%. Statistical analysis showed an accuracy between the IHC profile and the MP of 70.27%. The use of the IHC profile, when compared with the MP/BP, showed a sensitivity of 66.7% and a specificity of 72.7%. Of the 14 patients at high risk due to MP, 2 did not undergo chemotherapy treatment. All patients (at high and low risk) received adjuvant endocrine therapy with an aromatase inhibitor. After 42 months of medium FU, all patients were alive and disease-free, inferring DFS and OS of 100%. Conclusions: the analysis of data and outcomes in the elderly population of the AGEMA-BRA study with high clinical risk, demonstrated limited accuracy and low agreement in the stratification into high and low risk between the profile by IHC and the MP/BP. The use of the genomic platform may have been relevant in risk stratification and outcomes in this population. Studies with a larger sample and longer FU are needed to confirm the usefulness of genetic signatures in the de-escalation of systemic treatment in the elderly population with high clinical risk.
Clinical and biological heterogeneity in triple-negative breast cancer and HER2-low.
Authors: Hu Xi'e , Yang Ping , Chen Songhao , Wei Gang , Yuan Lijuan , Yang Zhenyu , Yang Lin , Peng Shujia , Dong Yanming , He Xianli , Bao Guoqiang 
Published: June 2023

e12565 Background: HER2-low could be found in some patients with triple-negative breast cancer (TNBC). However, its potential impacts on clinical features and tumor biological characteristics in TNBC remain unclear. Methods: We enrolled 251 consecutive TNBC patients retrospectively, including 157 HER2-low (HER2low) and 94 HER2-negtive (HER2neg) patients to investigate the clinical and prognostic features. Then, we performed single-cell RNA sequencing (scRNA-seq) with another seven TNBC samples (HER2neg vs. HER2low, 4 vs. 3) prospectively to further explore the differences of tumor biological properties between the two TNBC phenotypes. The underlying molecular distinctions were also explored and then verified in the additional TNBC samples. Results: Compared with HER2neg TNBC, HER2low TNBC patients exhibited malignant clinical features with larger tumor size ( P = 0.04), more lymph nodes involvement ( P = 0.02), higher histological grade of lesions ( P < 0.001), higher Ki67 status ( P < 0.01), and a worse prognosis ( P < 0.001; HR [CI 95%] = 3.44 [2.10-5.62]). Cox proportional hazards analysis showed that neoadjuvant systemic therapy, lymph nodes involvement and Ki67 levels were prognostic factors in HER2low TNBC but not in HER2neg TNBC patients. scRNA-seq revealed that HER2low TNBC which showed more metabolically active and aggressive hallmarks, while HER2neg TNBC exhibited signatures more involved in immune activities with higher expressions of immunoglobulin-related genes ( IGHG1, IGHG4, IGKC, IGLC2); this was further confirmed by immunofluorescence in clinical TNBC samples. Furthermore, HER2low and HER2neg TNBC exhibited distinct tumor evolutionary characteristics. Moreover, HER2neg TNBC revealed a potentially more active immune microenvironment than HER2low TNBC, as evidenced by positively active regulation of macrophage polarization, abundant CD8+ effector T cells, enriched diversity of T-cell receptors and higher levels of immunotherapy-targeted markers, which contributed to achieve immunotherapeutic response. Conclusions: This study suggests that HER2low TNBC patients harbor more malignant clinical behavior and aggressive tumor biological properties than the HER2neg phenotype. The heterogeneity of HER2 may be a non-negligible factor in the clinical management of TNBC patients. Our data provides new insights into the development of a more refined classification and tailored therapeutic strategies for TNBC patients.
Use of tumoral LDH to predict residual tumor burden after neoadjuvant chemotherapy in breast cancer.
Authors: Lee Soo Jung , Lee In Hee , Kang Byeongju , Park Jee-Young Nora , Lee Jeeyeon , Park Ho Yong , Park Ji-young , Chae Yee Soo 
Published: June 2023

e12566 Background: The Residual Cancer Burden (RCB) score has been validated as an independent prognostic factor in all subtype of breast cancer after neoadjuvant chemotherapy (NAC). Early prediction of NAC response enable better stratification for selecting chemotherapy. Glucose metabolism in cancer cells produces various glycolytic metabolites which are related to breast cancer prognosis. In this study, we evaluated the association of glucose transporters and enzymes involved in glucose metabolism with clinic-pathological factors for early prediction of NAC response. Methods: RCB scores were retrospectively evaluated from patients with stage I-III breast cancer treated with neoadjuvant chemotherapy. We selected 7 target transporters and enzymes [GLUT1, hexokinase 2 (HK2), lactate dehydrogenase (LDH), MCT1, MCT4, IGF1RA, and IGF1RB] involved in glucose metabolism and evaluated in relationships with pretreatment clinical/pathological characteristics and treatment outcomes including RCB. Results: 236 breast cancer patients who underwent NAC followed by surgery between 2010 and 2016 in Kyungpook National University Chilgok Hospital were included. Among them, 145 (61.4%), 44 (18.6%), and 47 (19.9%) were luminal, HER2-enriched, and TNBC subtypes. RCB 0 was determined 50 (21.2%), 35 (14.8%) RCB I, 91 (38.6%) RCB II and 60 (25.4%) RCB III. After a median follow-up of 98 months, 60 (25.4%) relapses, 43 (18.2%) distant relapses, and 34 (14.4%) deaths were observed. RCB score was significantly associated with disease specific survival (DSS) and overall survival (OS). RCB III were significantly increased risk of relapse (HR=13.517, CI [1.809-101.010], P<0.001). The tumoral expression rates of the target molecules were 76.0, 31.1, 42.1, 54.9, 67.9, 78.4, and 49.8% for GLUT1, HK2, LDH, MCT1, MCT4, IGF1RA, and IGF1RB, respectively. Among them, LDH was significantly associated with RCB III (OR=4.533, P=0.014) and worse disease specific survival (HR=2.29 P=0.019). Conclusions: Tumoral expression of LDH could be considered as an independent biomarker in predicting high risk of relapse (RBC III) and survival in all subtype of breast cancer.
Treatment patterns and clinical outcomes of newly diagnosed early-stage and locally advanced triple negative breast cancer (TNBC): A retrospective cohort analysis of national real-world data in England.
Authors: Barham Manpreet , Ntais Dionysios , Macey Karen , Murray Kirsty , Castillo Catherine , Ford Alexander , Patel Amisha , Holbrook Tim 
Published: June 2023

e12577 Background: TNBC patients have poorer survival outcomes when compared to other types of breast cancer, due to the lack of treatment options available and the aggressiveness of the disease. The current standard of care for early-stage TNBC is neoadjuvant pembrolizumab in combination with chemotherapy followed by pembrolizumab monotherapy after surgery (KEYNOTE-522), however prior to this treatment options and outcomes have been relatively limited compared to hormone receptor- and HER2- positive breast cancers. This study aimed to describe the treatment patterns and clinical outcomes of early-stage and locally advanced TNBC patients in England before the approval of KEYNOTE-522. Methods: In this retrospective cohort study, data from the English National Cancer Registration and Analysis Service databases (Cancer Registry, Systemic Anti-Cancer Therapy, Hospital Episode Statistics [HES], National Radiotherapy Dataset and Diagnostic Imaging Dataset) were used. Adults with a first record of primary early-stage or locally advanced TNBC (stage II – IIIb) between 01/01/2015 and 31/12/2018 were indexed. Treatment pathways and clinical outcomes were investigated over a maximum of 5-years follow-up period extending to December 2020. Outcomes were described descriptively. Results: A total of 3,475 patients met the inclusion criteria for the newly diagnosed TNBC cohort. 82.7% and 17.3% of patients were diagnosed at stage II and stage III respectively and, 83.3% were of white ethnicity, and 46.6% were node positive. Around 80% of patients had a primary surgery performed (i.e. a mastectomy or breast conserving surgery). Anthracyclines were the most common drug type used as a first regimen in both the neoadjuvant and adjuvant settings. During the follow up period, 37.7% and 15.3% of patients experienced locoregional or distant metastatic progression, respectively and 22.6% died. Median OS or EFS was not reached as < 50% patients died within the 5-year follow up period. The 5-year OS and EFS rate was ~57% and ~60%, respectively. Increased healthcare resource utilisation (HCRU) with associated high costs was reported in the time periods post diagnosis. The mean number of TNBC-related inpatient stays was the highest in the 3 to 6 months following index; 3.77 (SD = 3.95), costing a total of £4,992,150.48 (per patient cost: £1,458.84 [£1918.76], mean [SD]). Conclusions: This is the first real world evidence study using the England NCRAS datasets to assess the outcomes of the early-stage and locally advanced TNBC population in England. Treatment plans were heterogenous in TNBC patients and probability of survival was poor. This highlights the need for improvement of the treatment options and thus clinical outcomes of this patient population.
Reflex MammaPrint testing on breast core biopsies: A single center experience.
Authors: Kerrigan Colleen , Look Hong Nicole , Roberts Amanda , Nofech-Mozes Sharon , Jorden Tanya , Gandhi Sonal 
Published: June 2023

e12581 Background: Breast cancer genomic assays are well established in the adjuvant setting, but still evolving in the neoadjuvant setting. Recent data shows that MammaPrint (MP)/BluePrint (BP) genomic assays in the neoadjuvant setting can reclassify hormone receptor positive (HR+), HER2 negative (HER2-) tumors into intrinsic phenotypes with corresponding responses to neoadjuvant therapy (NAC). We performed reflex MP/BP assays on invasive breast cancer core biopsies and evaluated the relationships between clinical risk, molecular risk and intrinsic phenotype. Methods: 150 consecutive HR+, HER2- invasive breast cancers were identified by core biopsy in a tertiary care cancer center and underwent reflex MP/BP testing by an external central laboratory between July 2021 and Jan 2022. Retrospective review was completed on patient demographics and tumor characteristics; descriptive statistics were performed. Results: Of 150 newly diagnosed HR+ HER2- breast cancers, 141 successfully had a reflex MP/BP test performed; 9 were not performed due to technical feasibility or clerical error. Of the 141 patients with a completed MP/BP assay, 7 had recurrent disease, and 8 had metastatic disease, these were excluded. Patients were categorized as clinically high (cHR) or low risk (cLR) using the criteria from the MINDACT trial and as molecularly high risk (MP HR) or low risk (MP LR) per their MP results. We then grouped patients with discordant clinical and molecular risk. We then examined clinical features and NAC receipt amongst these clinical and molecular risk groups. Conclusions: There was discordance between clinical and molecular risk in 38% of our cohort, 20% were cLR/MP and 18% were cHR/MP LR. The decision to give NAC was primarily driven by clinical risk as only 1 patient with cLR/MP HR received NAC. Amongst cHR/MP LR 87% did not get NAC, but this appears to have been a clinical decision as only 7 of these patients had a pre-operative oncology visit at which MP/BP was mentioned. Most (72%) of > cN1 patients received NAC, of the 5 who didn’t, 4 were in the MP LR group and had a pre-operative oncology visit where MP was mentioned. In this select group the genomic assay may have influenced the decision to withhold NAC. Reflex genomic assays for HR+ HER2- breast cancer may not be useful; the decision to integrate molecular risk into the decision for NAC is multifactorial and stage of disease may be most impactful. Further work is needed in this area. [Table: see text] [Table: see text]
Efficacy comparison of anthracycline and taxane when added to immune checkpoint inhibitor in neoadjuvant chemotherapy of triple negative breast cancer: Clinical evidence from size-reduction measurement by ultrasound.
Authors: Chen Shin-Cheh , Shen Shih-Che , Yu Chi-Chang , Chang Hsien-Kun , Lin Yung-Chang , Chen Jen-Shi , Lo Yun-Feng , Kuo Wen-Lin , Tsai Hsiu-Pei , Chou Hsu-Huan , Chu Chia-Hui , Shen Wen-Chi , Wu Ren-Chin , Ueng Shir-Hwa , Huang Yi-Ting 
Published: June 2023

e12584 Background: Most chemotherapeutics can improve responses to immune checkpoint inhibitors (ICI) by increased immunogenicity. Anthracycline(AC), taxane(T) and platinum (CDDP) has most direct cytotoxic effect in neoadjuvant chemotherapy (NAC) of triple negative breast cancer (TNBC), but which one deserve the most immunostimulatory activity linked to their capacity of to kill cancer cell still unknown. Methods: A total of 91 patients with complete data of size measurement by ultrasound (US) were identified for the study from 363 consecutive TNBC patients received NAC between November 2010 to August 2022. They were divided into 3 groups. The 1st group patients received AC first, then T with CDDP, 2nd group in reverse sequence (T and CDDP first) and 3rd group, sequence as group 2 but adding ICI (pembrolizumab). Tumors size measured by US before chemotherapy, after 1st and after 2nd regimen of chemotherapy. Percentage of size reduction of tumor maximal diameter (cm), surface area (transverse x longitudinal diameter, cm2) and volume (measured by 1/6 p x transverse x longitudinal x height cm3) were calculated. Statistically significant was calculated using the Mann-Whitney U test for percentage of size reduction and Pearson's chi-squared test for pCR rate, p-value < 0.05 was considered significant. Results: There were 14, 56 and 21 patients in group 1, 2 and 3, respectively. The significant difference of pathologic complete response rates 7.1%, 44.6% and 76.2% in each group as shown. The volume, surface area and maximal tumor size reduction percentage after 1st regimen chemotherapy in group 1 (AC), group 2 (T+CDDP) and group 3 (ICI+T+CDDP) were -67.24, -55.43, -31.13; -85.45, -72.13, -45.61 and -87.13, -69.75, -45.02, respectively, and size reduction after 2nd regimen chemotherapy in group 2 (AC) were, -42.19, -30.19, -21.13; and group 3 (ICI+AC) were -77.78, -50.76, -30.65; respectively. A statistical non-significant trend of greater size reduction in ICI+ AC than AC alone was found. Conclusions: The study is the first, direct evidence demonstrated the synergistic effect of size reduction after NAC for TNBC with AC and ICI, but not T. It supports the potential benefit of combining chemotherapy with immunotherapy such as Tonic trial reported. [Table: see text]