bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic subset of metastatic and non-metastatic luminal B breast cancer (LBBC) subtype based on Ki67 index.
Authors: Puii Lalnun , Sangi Lalram , Varayathu Hrishi , Koramati Samuel Luke , Thomas Beulah Elsa , Mathew Smruthy Ann , Somayaji Shalaka , Thungappa Satheesh Chiradoni , Bj Sriniivas , Munirathnam Vinayak , Swamy Shivakumar , BN Tejaswini , Mufti Suhail Sayeed , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah 
Published: June 2021

e12570 Background: Gene expression profiling for breast cancer has classified ER positive subtype into luminal A and luminal B. Luminal B breast cancer (LBBC) have a higher proliferation and poorer prognosis than luminal A tumors. Ki-67 index is the commonly used proliferation marker in breast cancer; however Ki67 expression can also be used to identify a subset of patients among LB with a favorable prognosis. This study attempts to verify this subset of LBBC patients based on DFS and PFS in non-metastatic and metastatic patients respectively. Methods: We retrospectively analyzed 80 IDC breast cancer patients diagnosed in 2013-2016 with complete follow-up till January-2021. We defined LBBC as ER+, PR+ or PR- , HER2+ or HER2- with a Ki67 index >20%. PFS was considered as the endpoint in patients presenting with metastatic disease whereas DFS was used in non-metastatic disease. The cut-off for ki67 was calculated using an X-tile plot (version 3.6.1, Yale University) by dividing Ki67 data into two populations: low and high, with randomized 1:1 “training” and “validation” cohorts. Results: Median age was 51.5 years. 18.7% (n=15) presented with metastasis at the time of diagnosis and their overall median PFS was found to be 25.8 months. The incidence of HER2 positive LBBC was found to be 15% (n=12) and none of them were found to be presented with metastasis. Survival and frequency of various sub groups in our study are enlisted in the given table. We estimated a Ki67 cut-off of 30% in patients with upfront metastatic disease and PFS was found to be higher in <30% compared to a Ki67 index >30% (38.9 months vs 19.7 months, p-0.002). Overall median DFS was not achieved in non-metastatic group (Mean DFS: 64.7 months) where as a statistically significant difference was observed in the survival of HER2 positive (median DFS: 53.5 months, mean DFS: 50.9) than HER2 negative patients (median DFS not achieved, mean: 66.97 months) ( p-0.021). We obtained a Ki67 cut-off of 32% in non- metastatic group and mean DFS was found to be higher in Ki67<32% (69 months) compared to Ki67>32% (61.4 months), however it failed to exhibit a statistically significant relationship ( p-0.373). Conclusions: Our study indicates that a subset of patients exists within metastatic and non-metastatic LBBC with differing prognosis based on Ki67. Larger studies are further required to confirm the findings and therapeutic implications.[Table: see text]
Predictive value of topoisomerase II alpha protein for clinicopathological characteristics and prognosis in early breast cancer.
Authors: Yun Wu , Han Yiqun , Xu Hangcheng , Li Qing , Xu Binghe , Zhang Pin , Yuan Peng , Ma Fei , Luo Yang , Fan Ying , Chen Shanshan , Cai Ruigang , Li Qiao , Wang Jiayu 
Published: June 2021

e12586 Background: Topoisomerase II alpha (TOP2A) has been identified as a proliferation marker, of which the most common method for detection is immunohistochemistry (IHC). However, the optimal cut-off of TOP2A expression regarding prognostic value remains controversial. This study was to identify the optimal cut-off value of TOP2A expression and its correlation with clinicopathological variables and prognosis in early-stage breast cancer in China. Methods: Between January 2013 and January 2015, a total of 1084 early breast cancer patients were enrolled. The optimal cut-off of TOP2A expression was assessed using the minimum P value approach. Correlations between TOP2A expression and clinicopathological characteristics were explored by the Spearman’s correlation analysis, while the impact of TOP2A expression on disease free survival (DFS) and overall survival (OS) was evaluated by the Kaplan-Meier methods. Univariate and multivariate Cox regression analyses were executed to identify statistically significant prognostic factors. Results: The optimal cut-off value of TOP2A was recommended as 15%. Overall, 603 (55.6%) patients were TOP2A over-expression and 481 (44.4%) patients were TOP2A low-expression. TOP2A over-expression was in positive associations with a higher ki67 index (r = 0.83, P < 0.001), HER2 positive (r = 0.24, P < 0.001), a larger tumor size (r = 0.15, P < 0.001), and a higher histologic grade (r = 0.59, P < 0.001), and in a significantly negative correlation with hormone receptor (HR) positive expression in early breast cancer (r = -0.40, P < 0.001). TOP2A over-expression significantly associated with worse DFS (P = 0.001) and OS (P < 0.001) and was an independent prognostic factor for both DFS (hazard ratio [HR] = 1.71; 95% confidence interval [95%CI]: 1.13-2.59, P = 0.02) and OS (HR = 3.53; 95%CI: 1.53-8.23, P = 0.003) in stage I-II breast cancer patients. Conclusions: To our knowledge, this is the first study to recommend the optimal cut-off value of TOP2A expression in breast cancer. The TOP2A expression is significantly correlated with HER2 status, ki67 index, tumor size, histologic grade, and HR status, and could be a surrogate indicator for poor prognosis of early breast cancer.
Combination of individual tumor gene expression profiles and quantitative ultrasound and mammography imaging to understand the response to neoadjuvant chemotherapy among Hispanic-Latina women with early stages of triple-negative breast cancer.
Authors: Philipovskiy Alexander , Gaur Sumit , Chambers Karen , Gamez Roberto , Aguilera Renato , Ayyappan Anoop , Roy Souvrav 
Published: June 2021

e12605 Background: Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) characterized by the absence of targetable receptors. Traditionally, neoadjuvant chemotherapy (NACT) has been used to downstage the tumors and increase the chance for breast-conserving surgery. The pathological complete response (pCR) has been traditionally considering the best predictive marker for the disease recurrence. Patients with residual disease (RD) have a poor prognosis with a high risk of recurrence, and therefore additional chemotherapy was recommended. Therefore it is an important task for clinical researchers to identify markers to predict the individual tumor response to chemotherapy and avoid in patients potentially resistant tumors. Instead, a surgical approach can be used or combined approach with chemotherapy and immunotherapy. It is not clear yet which approach is optimal for those patients with chemotherapy-resistant tumors since there is no clinical data available and no clinical tool that helps predict the individual tumor response. In this study, we examined breast ultrasound(US) images of patients before and after the completion of NACT and correlated with response to chemotherapy. To better understand the biology of resistance to chemotherapy, we also analyzed the gene expression profile of 15 patients with RD after NACT. Methods: In this study, we retrospective analyzed breast US data from 37 Hispanic patients diagnosed with TNBC and treated with NACT. Patients underwent breast US before and after NACT with documentation of clinical complete response (cCR) or clinical residual disease (cRD). Post-operatively, the pathologic response was defined as the absence of tumor cells (pCR) or presence of residual invasive tumor (RD). A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR. Also, we analyzed formalin-fixed paraffin-embedded tumor samples from 15 patients with RD after NACT. Results: Seventeen patients (45.9%) achieved pCR, and twenty (54.1%) had RD after NACT. The most common US findings connected with RD was the deposition of calcium before NACT six (30%) patients. Gene expression analysis of RD samples identified 446 upregulated and 275 downregulated genes. Among commonly upregulated genes related to cancer, we identified GLI1, IGF1, SERPINE1, ATF3, KLK 5; 7, and TUBB2b, and genes belonging to pathways encoding extracellular matrix–related proteins, DNA-damage response proteins, and pathways related to resistance to chemotherapeutic agents such as Taxol. Conclusions: Our data suggested that gene expression profiling in combination with imaging study can be used to identify patients with TNBC potentially resistant to chemotherapy.
Does fertility preservation affect the start of the oncological treatment and the response to neoadjuvant chemotherapy in breast cancer.
Authors: Baulies Sonia , Izquierdo Maxim , Devesa Marta , Rodriguez Ignacio , Tresserra Fransec , Fabregas Rafael 
Published: June 2021

e12613 Background: Study in breast cancer patients to assess whether fertility preservation (FP) can affect the onset of the oncological treatment and the pathological response in those patients who underwent neoadjuvant chemotherapy (NAC). Methods: Patients with breast cancer who underwent fertility preservation and NAC are matched 1:2.45 to non-FP controls by age and date al diagnosis and are studied: -Timing between the diagnosis of breast cancer and the onset of oncological treatment was performed. The following variables were chosen: 1.- Confirmation (pathologic result), 2.- FP visit, 3.- Onset FP, 4.- Final FP, 5. – Onset oncological treatment. The periods analyzed (median in days) were: 1.- Period of FP visit (AP result-FP visit), 2.- Period of FP (FP beginning –FP ending), 3.- Period of onset of oncological treatment (FP ending-onset of oncological treatment), 4.- Overall period (AP result-onset of oncological treatment). -Studying the pathological complete response (Miller Payne scale) among patients with FP compare to non-FP control group was also performed. Results: 20 patients with FP and NAC are studied between 2010-2019 and were compared to 49 non-FP patients. The median age at diagnosis was 36 years (28-39). The oncological characteristics of the patients are shown in Table 1. The time analysis in FP group was: 1.- Period of FP visit was 4 days (1-26), 2.- the period of FP (start of the stimulation treatment until the recovery of the oocytes) 12 days (7-20), 3.- the Period of onset of oncological treatment 7 days (1-27). The overall period took 26 days (18-51) compared to 17.5 days (1-60) in non-FP group (NS). Pathological complete response (Miller Payne 5): The pathological complete response was 80% (16/20) in FP group versus 40.8% (20/49) in non-FP group. Analyzed by tumor subtype in FP group, a MP5 was achieved in 72.7% luminal tumor (8/11), 75% positive-HER2 (3/4), 100% triple negative (5/5) versus 19% luminal tumor (4/21), 41.6% (5/12) positive-HER2 and 68.7% triple negative (11/16) in non-FP group. Conclusions: FP does not delay the onset of oncological treatment and our data do not suggest an adverse impact of FP on pathological complete response to NAC. [Table: see text]
Association of tumor infiltrating lymphocytes with pathological response after neoadjuvant therapy in breast cancer: A retrospective study.
Authors: Grover Punita , Phan Kim , Magge Tara , Chou Andrew , Naffouje Rand , Jandarov Roman , Grate Lisa , Hinrichs Benjamin H , Charif Mahmoud 
Published: June 2021

e12621 Background: Tumor infiltrating lymphocytes (TILs) are thought to represent favorable host anti-tumor immunity and play an important role in mediating response to chemotherapy in breast cancer. TILs are heterogenous across breast cancer subtypes and are increasingly being studied as prognostic and predictive biomarkers. We undertook a retrospective study to establish the relationship between pre-treatment density of TILs and subsequent quality of response to neoadjuvant chemotherapy in patients with early-stage breast cancer. Methods: We retrospectively identified women with breast cancer who had received neoadjuvant therapy (NAT) at the University of Cincinnati from 2012-2018. Clinical and pathological variables were extracted from medical records. Pre-treatment core biopsies were assessed for intra-tumoral TILs through independent pathology review and were graded as mild (grade 1), moderate (grade 2) or severe (grade 3). Post-treatment resection samples were assessed for pathological complete response (pathCR). Univariate analysis was done to determine the association between TILs and pathCR. Results: We identified 148 patients with breast cancer who received NAT, median age 53 years (25-90), 77 were Caucasian. 32 patients had stage I disease at diagnosis, 87 stage II and 29 stage III. Most patients had tumor grade 2 (n=50) or 3 (n=91). 50 patients were HER2+, 65 ER/PR+ HER2- (HR+) and 33 had triple negative breast cancer (TNBC). 69 patients received anthracycline based NAT, 29 non-anthracycline based NAT and all HER2+ patients received anti-HER2 therapy. 72 patients had TILs grade 1, 54 grade 2 and 22 had grade 3. 50 patients achieved pathCR. On univariate analysis grade 2 and 3 TILs were associated with higher likelihood of pathCR compared to grade 1 (42.1% vs 25%, OR 2.18, [1.08 – 4.4], p = 0.029). There was no difference in pathCR between grade 2 and grade 3 TILs (40.7% vs 45.5%, OR 1.21 [0.45-3.29], p=0.12). Tumor grade 3 was associated with higher pathCR than grade 1 or 2 (41.8 vs 21.1%, OR 2.69 [1.26-5.75], p=0.01). Amongst breast cancer subtypes, pathCR was lower in HR+(13.8%) compared to TNBC (45.5%) or HER2+ (52%) with OR 0.15 (0.06-0.36), p<0.01. Age, race, stage and type of chemotherapy were not associated with pathCR. On multivariate analysis, none of the variables retained significance. Conclusions: Our analysis shows that increased TILs density (grade 2 or 3) and higher tumor grade are associated with pathCR whereas HR+ breast cancer have a lower rate of pathCR after NAT. Immune characterization of TILs might be helpful in further refining the prognostic impact of TILs.[Table: see text]
Analysis of disseminated tumor cells (DTCs) in primary breast cancer patients with various molecular subtypes.
Authors: Nel Ivonne , Weydandt Laura , Höhn Annekathrin , Aktas Bahriye 
Published: June 2021

e13000 Background: Despite successful treatment of the primary tumor, recurrence occurs in about 30% of breast cancer patients. One reason might be hematogenous spread during early disease stages. Disseminated breast cancer cells (DTCs) preferentially migrate into the bone marrow (BM) at early stages of the disease. Due to low proliferation, DTCs are persistent against systemic chemotherapy and might cause metastatic relapse at a later stage. Methods: BM aspirates were collected from the anterior iliac crest of patients with primary mamma carcinoma during surgery. After density gradient centrifugation cell suspensions were transferred onto glass slides and subjected to immunocytochemical staining against pan-cytokeratin. DTCs were visualized in pink using alkaline phosphatase and short counterstaining with hematoxylin which colored the nuclei light blue. DTCs were semi-automatically detected and enumerated using the Aperio Versa microscope based scanning system with a rare events algorithm that was trained to identify DTC candidates according to color, shape, intensity and size. As a positive control with each run, we used reference slides with a mix of bone marrow cells and a defined number of HCT116 cells. Results: Between February 2019 and December 2020 BM aspirates from 158 primary breast cancer patients were collected. Per patient about 4 million BM cells were analyzed. DTC detection revealed a positivity rate of 29% (46 patients). Molecular subtype analysis of DTC positive patients showed that 37% of the primary tumors (17 patients) were luminal A and 37% (17 patients) luminal B. In 9% of the cases (4 patients), tumors were HER2 enriched and 15% (8 patients) were triple negative. DTC count indicated that the majority of luminal B patients had 11-20 DTCs whereas luminal A patients tended to have lower DTC quantities varying between 1 and 10 DTCs. Conclusions: DTCs may serve as independent prognostic markers. Follow-Up data might reveal whether DTC quantification and molecular subtypes at primary diagnosis can be used to stratify patients at elevated risk for recurrence.
Cardiac function in patients receiving dual anti-Her2 antibodies (trastuzumab and pertuzumab) combined with chemotherapy for breast cancer in routine practice.
Authors: Zekri Jamal , Rasool Haleem J. , Rizvi Syed Azhar J , Mahmoud Ehab Mosaad Abdel Ghany , Rasmy Ayman Ahamd , Al-Gahmi Aboelkhair , Farag Kamel 
Published: June 2021

e13009 Background: Chemotherapy regimens (C) containing a combination of anti-Her2 antibodies are associated with a risk of cardiac toxicity in landmark clinical trials. We evaluate the cardiac function of patients with Her2 over-expressed (Her2OE) breast cancer (BC) receiving C combined with trastuzumab (T) and pertuzumab (P) in routine clinical practice setting. Methods: The initial cohort of patients who started C in combination with TP (CTP) in standard doses and schedules before September 2019 in 4 cancer units were included. All patients had regular measurement of left ventricular ejection fraction (LVEF) by Doppler ultrasound studies. Data was collected retrospectively and was limited to the first 24 months after initiation of CTP treatment. The paired sample T-test was used to test the significance of the difference in LVEF. Results: Sixty seven patients were identified. CTP treatment was administered in the neoadjuvant and palliative settings in 28 (41.8%) and 39 (58.2%) respectively. None of the patients received concomitant anthracycline with TP. All patients underwent LVEF assessment prior to starting CTP treatment and at 3 and 6 months later. Subsequently LVEF was measured at 9, 12, 15, 18, 21 and 24 months as long as patients are still receiving CTP treatment (table). LVEF was measured in 11 patients for 24 months. Compared to baseline, mean LVEF was not significantly different at any of the subsequent time points (range; decrease by -0.936% to increase by 1.087%) (Table). Dual anti-Her2 antibodies (TP) administration was omitted temporarily once for 2 patients due to clinically suspected cardiac toxicity which was excluded on further investigations. Conclusions: In this cohort describing our limited initial experience, dual anti-Her2 antibodies (T&P) combined with chemotherapy is not associated with significant cardiac toxicity when LVEF is measured every 3 months. Further studies investigating less frequent LVEF monitoring (e.g. every 5-6 months) may be warranted.[Table: see text]
First-line treatment with a cyclin-dependent kinase 4/6 inhibitor combined with an aromatase inhibitor for hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer: Population-based outcomes for patients treated in Alberta, Canada.
Authors: Amaro Carla Pires , Batra Atul , Lupichuk Sasha M. 
Published: June 2021

e13020 Background: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in combination with an aromatase inhibitor (AI) has emerged as the standard first line treatment in patients with hormone receptor positive, human epidermal growth factor receptor-2 (HER-2) negative metastatic breast cancer (MBC). In this analysis, we describe population-based outcomes for first-line treatment with a CDK4/6i combined with an AI. Methods: All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 in a large Canadian province were included. Descriptive statistics were used to summarize patient demographics, tumor and treatment characteristics. Survival distributions were estimated using the Kaplan-Meier method. Multivariate analysis (MVA) using a Cox proportional hazards model was constructed to examine associations between potentially prognostic clinical variables and progression free survival (PFS). Results: A total of 316 patients were included. Median age was 61 years (interquartile range, 53-70 years), 82% were postmenopausal women, 39% had de novo MBC, and 48% had non-visceral disease. Palbociclib was prescribed in 94% of patients and the remaining patients received ribociclib. The CDK4/6i was dose-reduced upfront or during treatment in 47%. While 70% of the patients discontinued treatment due to progression, 30% stopped due to toxicity/patient preference/physician recommendation. With a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7-NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45-3.88; P = 0.001) and dose reduction of the CDK4/6i (HR, 1.51; 95% CI, 1.06-2.16; P = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed (n = 131), 89% received second-line treatment (chemotherapy in 46%, single agent hormonal therapy in 35%, hormonal therapy plus a targeted agent in 15%, and other in 4%). Median time to progression on second line chemotherapy was 9.0 (5.8-17.6) months and second line hormonal therapy +/- targeted agent was 4.0 (3.4-8.6) months (P = 0.012). Conclusions: The real-world outcomes of first-line use of CDK4/6i and AI are encouraging. PR negative tumors and dose reduction appear to be negative prognostic markers. CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favorable PFS and early OS outcomes.
Initial real life experience with ribociclib in breast cancer: Outcome with focus on tolerance and cardiac toxicity.
Authors: Nawaz Azhar , Zekri Jamal , Rasool Haleem J. 
Published: June 2021

e13024 Background: CDK4/6 inhibitors, such as ribociclib, are a new class of medications that are used in combination with hormonal therapy to treat advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. The primary objective of this study is to evaluate the tolerance and cardiac toxicity of ribociclib in all patients at our institution. Secondary objectives include progression free survival and response rates. Methods: Patients who received ribociclib between December 2018 and August 2020 were included. Rates of dose reduction and discontinuation of ribociclib were used as surrogate markers for intolerance and were compared to those reported in land-mark trials. QTc changes and cardiac adverse events (AEs) were also collected. Results: Thirty one patients were included. Ribociclib was administered in the first-, second-, third-, and fourth-line palliative hormonal therapy settings in 5 (16%), 14 (45%), 11 (35%) and 1 (3%) patients respectively and 8/31 (26%) received prior 1-4 palliative chemotherapy lines. Ribociclib was combined with letrozole in 21 (68%) and with fulvestrant in 10 (32%) patients. QTc interval was ≤ 470 msec in all patients prior to treatment and 11 (35%) patients had preexisting cardio vascular (non electro-conductive) co-morbidities. AEs related dose reduction was reported in 12 (39%) patients [bone marrow toxicity 6 (19%), QTc prolongation 4 (13%), abnormal liver function tests 1 (3%) and abdominal pain 1 (3%)]. Ribociclib was permanently discontinued due to AEs in 5 (16%) patients (2: prolonged QTc, 2: coronary events and 1: suspected allergic reaction). The median duration of follow up was 14 months. Objective response was evaluable in 28 patients [CR: 1 (3.6%), PR: 1 (3.6%), SD: 20 (71.4%) and PD: 6 (21.4%)]. The median progression free survival was 18 months (95% CI: 12.3-23.7). Conclusions: Although objective response rates were low in this mixed cohort of heavily pretreated patients, ribociclib combined with letrozole or fulvestrant has shown a robust progression free survival in real life practice. Treatment discontinuation rate is higher than that reported in clinical trials with stringent inclusion criteria. Ribociclib associated cardiac toxicity can be appropriately managed with careful monitoring.[Table: see text]