bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fragement C Gamma receptor IIIa polymorphism is predictive of trastuzumab efficacy in the neoadjuvant setting of HER2-positive breast cancer patients.
Authors: Lee Kaping , Luo Rongzhen , Wang Shusen , Xu Fei 
Published: June 2022

e12607 Background: Antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the most important mechanisms of Trastuzumab. Fragement C Gamma receptor (FcγR) IIA and IIIA polymorphisms influence the affinity of immunoglobin G (IgG). Recently, FcγRIIA and FcγRIIIA polymorphisms have identified with the efficacy of trastuzumab. However, whether FcγR polymorphisms are associated with the efficacy of trastuzumab in the neoadjuvant setting was unclear. Methods: We retrospectively enrolled 101 patients with HER2-positive breast cancer receiving chemotherapy plus trastuzumab as neoadjuvant therapy and mastectomy in Sun Yat-sen university cancer center from May 2015 to March 2021. Among them, twenty patients were excluded because lacking of blood samples. Clinical and pathological characteristics, treatments and outcomes of patients were collected. We purified the genomic DNA from peripheral blood samples, performed nested polymerase chain reaction (PCR) and sanger sequencing to identify the polymorphisms of FcγRIIA(rs1801274) and FcγRIIIA(rs396991). Results: Patient samples (n=81) were successfully detected. No significant differences between FcγRIIA/FcγRIIIA genotypes and clinical characteristics, including age, clinical stage, menstrual status, molecular subtyping, treatment and pathological complete response (pCR) rate. In subgroup analyses, FcγRIIIA polymorphism was significantly correlated with pCR rate in the population who received paclitaxel plus trastuzumab therapy (n=34, P<0.05). The Kaplan-Meier analyses showed that no significant difference in disease-free survivals (DFS) between FcγRIIA-131 H/H and R carriers genotype groups ( P=0.24), either that in the FcγRIIIA-158 F/F and V carriers genotype groups ( P=0.60). But the DFS in FcγRIIIA-158 V carriers genotype group were significant longer than that in FcγRIIIA-158 F/F genotype group in subgroup who received paclitaxel plus trastuzumab therapy (n=34, P=0.036), while that was not significant difference in patients with anthracycline-based treatment (n=47, P=0.248). DFS has not yet been reached. Conclusions: FcγRIIIA polymorphism is predictive of trastuzumab efficacy in the neoadjuvant setting of HER2-positive breast cancer patients who received paclitaxel plus trastuzumab therapy. Anthracycline-based treatment may improve the outcomes of HER2 positive breast cancer patients with FcγRIIIA-158 F/F genotype.[Table: see text]
Influencing factors of the recurrence after neoadjuvant therapy in HER2-positive breast cancer.
Authors: Morales Murillo Serafin , Gasol Cud"S Ariadna , Tuset Der-abrain Noemí , Rodriguez Alvaro , Velasco Sanchez Ana , Vilardell Felip , Sanchez Guzman Douglas , Canosa Morales Carles , Olivé Jordi Melé 
Published: June 2022

e12608 Background: HER2-positive breast cancer is the more suitable subtype to perform a neoadjuvant therapy with chemotherapy and antiHER2 therapy because a high pathologic response and significance survival. However, despite this high percentage of pathological responses, there are still recurrences that can affect survival. Methods: We analyze a cohort of 287 HER-2 positive breast cancer treated with neoadjuvant chemotherapy and antiHER2 therapy according to current guidelines, to find the factors that could induce a recurrence. Results: Median age was of 56 (28-89), median tumor size of 37 mm (12-140), 145 (50%) had nodal involvement, estrogen receptor positive in 152 patients (53%) and median ki67 expression of 41% (3-95). HER2 expression by inmunohistochemistry was 2+ in 83 patients (29%) and 3+ in 204 (71%). A total of 50% complete pathological response (pCR) rate was detected and 54 (18,8%) relapsed. 17 patients with pCR (12%) and 37 patients without pCR (25%) had a recurrence (OR 4,31, p: 0,003). The factors that most influenced the relapse in the group of patients with pCR were: the initial size (greater than 5 cm) 30% of relapses, the initial axillary involvement (19%) and the cases with HER2 +3 expression and estrogen receptor negative (17%). In the group without pCR, the relapse was more frequent in patients with HER2 +2 expression and estrogen receptor negative (40%), HER2 +3 expression and estrogen receptor negative (43%), initial tumor size greater than 5 cm (38%) and axillary involvement (38%). Conclusions: Although pCR continues to be the most important factor to avoid relapse, there are other factors that must be considered as determinants of relapse despite achieving a pCR. Initial size greater than 5 cm is a poor prognostic factor despite reaching a pCR with up to 30% relapses, so other adjuvant interventions should be considered after initial neoadjuvant treatment.
Clinical N3 as an independent risk factor of recurrence for breast cancer patients achieving pathological complete response and near-pathological complete response after neoadjuvant chemotherapy.
Authors: Qian Xiaoyan , Zhang Pin , Xiu Meng , Li Qing , Wang Jiayu , Fan Ying , Luo Yang , Cai Ruigang , Li Qiao , Yuan Peng , Ma Fei , Xu Binghe 
Published: June 2022

e12619 Background: Although achieving pathological complete response (pCR) and near-pathological complete response (near-pCR) after neoadjuvant chemotherapy (NAC) in breast cancer predicts a better outcome, some patients still experience recurrence. The aim of our study was to analyse the predictive factors of recurrence in the pCR and near-pCR population. Methods: We reviewed 1209 breast cancer patients treated with NAC. A total of 292 patients achieving pCR and near-pCR between January 2010 and April 2021 in the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) were included in our analysis. pCR was defined as ypT0N0/ypTisN0. Near-pCR was defined as ypT1mi/1a/1bN0 or ypT0/isN1mi. The Kaplan-Meier method with the log rank test was used to estimate recurrence analysis. Results: Of the 292 patients,173 were pCR and 119 were near-pCR. The median age was 46 years (range 23-75 years). The predominant tumor subtype was human epidermal growth factor receptor type 2 (HER2) positive (49.0%) and triple-negative breast cancer (TNBC) (30.8%). The median duration of follow-up was 53 months (range 9-138 months). A total of 16 (8.9%) patients developed recurrence, with 9 (5.2%) in the pCR group and 16 (13.4%) in the near-pCR group. The vast majority of recurrence occurred within 36 months from onset of NAC. The 5-year recurrence-free survival (RFS) rate of patients achieving pCR was significantly higher than that of patients achieving near-pCR (94.6% vs.85.6%, P=0.008). Clinical N3 (cN3) before NAC was an independent factor of higher risk for recurrence in patients who achieved pCR ( P=0.003) and near-pCR ( P=0.036). Tumor size before NAC, subtype of breast cancer and chemotherapy regimens showed no significant association with RFS both for patients who achieved pCR and near-pCR ( P ≥0.05). Conclusions: cN3 before NAC was an independent factor of higher risk for recurrence in patients who achieved pCR and near-pCR. It is worthwhile to monitor closely for patients with cN3, especially in the first 3 years.
Lactate dehydrogenase as a surrogate marker for both PCR and survival in breast cancer patients who underwent neoadjuvant chemotherapy.
Authors: Lee In Hee , Chae Yee Soo , Lee Jeeyeon , Park Ho Yong , Jung Jin Hyang , Park Ji-young , Park Jee-Young 
Published: June 2022

e12621 Background: Glucose metabolism in cancer cells produces various glycolytic metabolites, which can affect cancer progression and treatment outcome. Herein we evaluated the association of glucose transporters and enzymes involved in glucose metabolism with clinic-pathological factors and outcomes in breast cancer patients who underwent neoadjuvant chemotherapy(NAC). Methods: We selected 7 target transporters and enzymes(GLUT1, hexokinase 2, lactate dehydrogenase, MCT1, MCT4, IGF1RA, and IGF1RB) involved in glucose metabolism. Their tumoral expressions were scored both quantitively and qualitatively based on tissue microarrays and immunohistochemistry as previously described (Pinheiro et al, 2010) and then evaluated in relationships with pretreatment clinical/pathological characteristics and treatment outcomes including findings of 18F-FDG PET/CT,pathologic complete response(pCR), and relapse in breast cancer(stage IIA-IIIC) patients who underwent anthracycline or taxane-based NAC. Results: Of the 236 enrolled patients, 145(61.4%), 44(18.6%), and 47(19.9%) were luminal, HER2-enriched, and TNBC subtypes. Pathologic CR was determined 50(21.2%) and 57(24.2%) relapses, 42(17.8%) distant relapses, and 28 deaths were observed during median follow-up duration of 64.0 (32.3-114.9) months. The expression rates of the target molecules were 76.0, 31.1, 42.1, 54.9, 67.9, 78.4, and 49.8% for GLUT1, hexokinase 2 (HK2), lactate dehydrogenase(LD), MCT1, MCT4, IGF1RA, and IGF1RB, respectively. Among target molecules in glucose metabolism, LD was significantly associated with pCR(OR = 0.251; p- = 0.016) and distant disease-free survival (HR = 2.29; P = 0.019). Plus, LD expression shows a trend for a high SUVmax of primary tumor 18F-FDG PET/CT(OR = 1.797 P = 0.060). Conclusions: Tumoral expression of lactate dehydrogenase can be considered as a predictive marker for pCR to NAC and plus prognostic marker for survival in patients with breast cancer.
Neutrophil-lymphocyte ratio and prediction of pathological complete response to neoadjuvant treatment in breast cancer.
Authors: Clarke Rachel , Lucas Mairi , Ryan Niamh , Walsh Siun , Mahon Sarah , Kelly Catherine Margaret 
Published: June 2022

e12627 Background: Pathological complete response (pCR) after neoadjuvant therapy in breast cancer is an important prognostic indicator for improved disease free survival. High tumour grade, low ER-status, HER2-positivity predict higher likelihood of a pCR however better predictive biomarkers are needed. The role of the immune system and specifically the presence of tumour infiltrating lymphocytes in increasing response to chemotherapy has been extensively studied across cancer subtypes2. We sought to determine if neutrophil-to-lymphocyte ratio (NLR) as a marker of immune inflammatory response could be informative in predicting likelihood of pCR. Methods: We identified a cohort of patients who had received neoadjuvant chemotherapy between 2012 to 2018. We extracted clinical, pathological and laboratory data for each case. A pretreatment peripheral blood test was used to calculate a neutrophil-to-lymphocyte ratio. We used R-studio to analyse our data. The primary objective was to determine if there was an association between NLR and pCR. Statistical analysis was performed to assess whether NLR ratio correlated with pCR. Results: We identified 107 patients who had received NAC for early stage breast cancer during our study period. The mean NLR in the cohort was 2.95 (range 0.76-11.9). 35 (32.7%) patients achieved a pCR. There was no statistically significant different in NLR in those who achieved pCR (n=35) and those who did not (n=72) (p value= 0.75). Patients with triple negative breast cancer (TNBC) had a higher rate of pCR (45.1%), compared to HER2-positive (42.1%) and ER-positive HER2-negative (25.4%). The NLR was not significant in predicting pCR within the separate histological cohorts. Conclusions: NLR did not predict for pathological complete response in our cohort. Further studies into the predictive value of NLR in this setting with larger cohorts are needed. Investigation into the dynamic changes of NLR both pre, post during treatment may provide further insights as may larger cohorts for analysis in each histological subtype.
Prognostic value of molecular response via ctDNA measurement in predicating response of systemic therapy in patients with advanced solid cancer.
Authors: Esmail Abdullah , Guan Jian , Xu Jiaqiong , Al-Rawi Hadeel , Parks Bethany , Al Saadi Noor , Khan Tanya , Madoux Laura , Taha Marwa , Abdelrahim Maen 
Published: June 2022

e13001 Background: Molecular profiling of cancer can guide treatment decision, monitor response and predict clinical outcome in the era of precision medicine and individualized treatment. Emerging evidence has suggested that ctDNA change correlates with treatment response and predates radiological relapse. Thus, we aim to provide real-world data regarding the dynamic changes of ctDNA level measured via Guardant 360 Response in advanced solid cancer correlates with clinical outcome. Methods: We retrospectively reviewed data of patients with advanced solid cancer and had at least 2 timepoints of Guardant 360 Response test at Houston Methodist Cancer center from 1/1/2014- 2 /1/2022. Data collected included age, gender, type of solid cancer, mutational values, treatment started date and type of systemic therapy. Personalized mutational profiles derived from tumor tissue via whole-exome sequencing were used to design patient-specific ctDNA assays for variant detection in plasma samples. Blood samples taken at baseline and 8 weeks were analyzed to a 70-gene next-generation sequencing panel. On-therapy changes in circulating tumor DNA levels (molecular response) were measured using a ratio computation, with response defined as a decrease in mean variant allele fraction of 50% or more. Apart from ctDNA analysis, patients were also monitored using tumor markers and radiological imaging. Results: : Of 267 patients, only 93 were met the inclusions criteria with age 58.66 (±12.95) and female were the most with 77 (82.80%). Patients with breast cancer were the dominant with 62 (66.67%), Lung adenocarcinoma 20 (21.51%), Uveal Melanoma 4 (4.30%), Colorectal Cancer and Lung Squamous Cell Carcinoma 2 (2.15 %) each, Large Cell Lung Carcinoma, Sarcoma and Thymic Carcinoma were 1(1.07%) each. Patients who received Chemotherapy /Immunotherapy were 38 (41.30%), Chemotherapy/Immunotherapy/Radiation therapy were 29 (31.52%), Immunotherapy 9 (9.78%), Chemotherapy/Immunotherapy/Targeted Therapy 2 (2.17%) and Targeted Therapy /Chemotherapy 3 (3.26%).Patients samples who correlated with clinical data were 89 (95.70%) and only 4 (4.30%) were not .Follow-up time 2.15 (interquartile range: 1.10-4.12) years, patients who still alive are 24 (25.81%), median survival time 2.4 (95% CI: 1.78-2.76) years. Conclusions: Our data demonstrated that molecular response evaluation using circulating tumor DNA as a noninvasive predictor of response to systemic therapy in addition to standard of care imaging in some solid cancer. Further prospective studies are needed to confirm the validation.
Integrated analysis of pivotal biomarker, immune cell infiltration, and therapeutic drugs for LSM1-mutated in breast cancer.
Authors: Tzeng Yen-Dun Tony , Sheu Jim Jinn-Chyuan , Li Chia-Jung 
Published: June 2022

e13011 Background: The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Methods: In the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of LSM1 in patients with breast cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of LSM1 proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichmente. Finally, we explored the mechanisms underlying LSM1 involvement in BRCA by using gene set enrichment analysis. Results: We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in BRCA patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease-free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib, and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer. Conclusions: In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for breast cancer.
Downregulation of ATP binding cassette subfamily a member 10 acts as a prognostic factor associated with immune infiltration in breast cancer.
Authors: Tzeng Yen-Dun Tony , Sheu Jim Jinn-Chyuan , Li Chia-Jung 
Published: June 2022

e13012 Background: The human ATP binding cassette (ABC) family of transporter proteins plays an important role in the maintenance of homeostasis in vivo. The aim of this study is to evaluate the potential diagnostic, prognostic, and therapeutic value of the ABCA10 gene in BRCA. Methods: In this study, a multi-step process was used to construct an immune-related genes (IRGs) based signature leveraging the expression profiles and clinical characteristics of BRCA from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. An integrated immunogenomic analysis was performed to determine the association between IRGs with prognostic significance and cancer genotypes in the tumor immune microenvironment (TIME). Moreover, we performed a comprehensive in silico therapeutics screening to identify agents with subclass-specific efficacy. Results: We found that ABCA10 expression was downregulated in different subgroups of breast cancer and strongly correlated with pathological stage in BRCA patients. Low expression of ABCA10 was associated with BRCA patients showing shorter overall survival (OS). ABCA10 expression may be regulated by promoter methylation, copy number variation (CNV) and kinase, and is associated with immune infiltration. Our study also demonstrated the potential role of ABCA10 modifications in tumor microenvironment (TME) cellular infiltration. Nevertheless, the regulatory mechanism remains unknown and immunotherapy is marginal in BRCA. We demonstrate the expression of different ABCA10 modulators in breast cancer associated with genetic variants, deletions, tumor mutation burden (TMB) and TME. Mutations in ABCA10 are positively associated with different immune cells in six different immune databases. Mutations in ABCA10 and immune cell infiltration play an important role in breast cancer. Conclusions: Overall, this study provides evidence that ABCA10 could become the potential targets for precision treatment and new biomarkers in the prognosis of breast cancer.
Safety and efficacy of monoclonal antibodies and tyrosine kinase inhibitors in advanced breast carcinoma.
Authors: Akbar Usman Ali , Vorla Mounica , Ashraf Aqsa , Poladi Keerthi , Qazi Shaheryar , Dab Ammar Yaser , Ijaz Hafsah , Azhar Ali Sibtain , Manahil Haider Jeoffrey Syeda , Akhtar Muhammad Ali Ali , Momin Ali 
Published: June 2022

e13017 Background: Novel drugs that target HER2 receptors have shown promise in the treatment of Advanced breast carcinoma (BC). We study here the safety and efficacy of select monoclonal drugs (Mab) and tyrosine kinase inhibitors (TKIs) in the treatment of advanced BC. Methods: Following the PRISMA guidelines, we searched the literature on PubMed, Cochrane, Embase & clinicaltrials.gov. A total of 1054 articles were screened, and 6 studies were included. Results: In a phase III trial comparing Margetuximab (MAR) vs Trastuzumab (TRA), the overall survival (OS) and Progression free survival (PFS) was superior for MAR (21.6m Vs 19.8m & 5.7m Vs 4.4m respectively). However, the side effect profile is comparable for both drugs.Neutropenia (50 %) was a key problem in an ongoing trial including Zenocutuzumab (ZENO), resulting in dosage reduction. Similarly, phase III trials incorporating TKIs such as Neratinib (NER) and Tucatinib (TUC), there was improved OS (21m Vs 18.7, 24.7m Vs 19.2m respectively) as compared to Standard of care and chemotherapy. Regarding safety profile, these therapies are generally well tolerated with manageable side effects as listed in the table. Conclusions: Both monoclonal antibodies and tyrosine kinase inhibitors show clinically significant benefits in advanced HER2 positive breast carcinoma. However, more evidence and randomized clinical trials are needed to further establish their role in this rapidly evolving field.[Table: see text]
HERibuline: Eribulin mesylate and Trastuzumab in pretreated HER2-positive advanced breast cancer—A report of region’s practice.
Authors: Gassian Noemie , Paget-Bailly Sophie , Djoumakh Oum El Kheir , Mansi Laura , Dobi Erion , Bazan Fernando , Curtit Elsa , Chaigneau Loic , Meneveau Nathalie , Paillard Marie-Justine , Selmani Zohair , Viot Julien , Borg Christophe , Meynard Guillaume 
Published: June 2022

e13020 Background: Until 2020, in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC), the two first lines of metastatic treatment were well defined but after, many options were possible, most often combining targeted therapy plus chemotherapy. Eribulin mesylate is indicated for the treatment of patients with ABC previously treated by anthracycline and taxane regimens in the advanced setting. Here, we present the results of eribuline and trastuzumab (E/T) combination in HER2-positive ABC previously treated. Methods: Patients with HER2-positive ABC treated with the E/T combination from our region cancer institute were included in this retrospective study. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR) and safety. Results: Between November 2013 and July 2019, a total of 34 consecutive patients with HER2-positive ABC were included. The median number of previous lines for advanced setting was 4 (range 2-7). Patients treated by taxanes and anthracyclines represented 91% and 47% respectively; 50%, 79% and 62% were previously treated with pertuzumab, trastuzumab emtansine and lapatinib respectively. After a median follow up of 24.8 months, median PFS was 6.2 months (95% CI [3.35-7.13]) and median OS was 12.6 months (95% CI [7.13-18.56]). The ORR and CBR were 38% and 53%, respectively. No unexpected adverse event was observed. The most frequent grade 3-4 toxicity was hematologic (44.1%). Conclusions: Recently, new therapies have revolutionized the management of HER2-positive ABC and patients benefit from a prolonged overall survival associated with a maintained performance status. However, in pretreated and advanced metastatic setting, there are few scientific evidence to guide the choice of treatments. A combination of E/T could be an effective option in patients with good performance status and willing to receive treatment.