bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hormones as indicator of relapse-free period in breast cancer (BC).
Authors: Samaneva Natalia Yu. , Frantsiyants Elena M. , Vladimirova Liubov Yu , Storozhakova Anna E. , Sheiko Elena A. , Bandovkina Valeria A. , Cheryarina Natalia D. , Tikhanovskaya Natalia M. , Kit Oleg I. , Lisutin Aleksandr E. , Shatova Iuliana S. , Vashchenko Larisa N. 
Published: May 2020

e12550 Background: BC is still one of the main causes of death in women due to the tumor recurrence and/or resistance to anticancer therapy. The criteria to assess the effectiveness of BC treatment are important. The purpose of the study was to analyze blood levels of steroid and pituitary hormones in BC patients after two chemotherapy cycles. Methods: The study included 42 patients with various biological BC subtypes: luminal A, luminal B and triple-negative BC (TNBC). Levels of estradiol, testosterone, progesterone, prolactin, LH, FSH and cortisol were measured by RIA in the blood of all patients before and after two neoadjuvant chemotherapy cycles. Significance of differences was evaluated by the Student’s t-test. Results: Levels of many hormones were high before the treatment in patients with all BC subtypes. After two chemotherapy cycles, unidirectional changes in the values were found in patients with subsequent remission for more than three years. Levels of estradiol decreased in luminal A BC by 1.7 times (p˂0.05), in luminal B BC – by 11.6 times (p˂0.05), cortisol decreased by 2.4 and 1.7 times (p˂0.05) respectively, and prolactin – on average by three times (p˂0.05). LH levels increased in luminal A and luminal B BC by 1.65 times (p˂0.05). In patients with TNBC, levels of estradiol decreased by 1.8 times, and cortisol – by two times (p˂0.05). Patients with subsequent remission regardless of BC subtypes had unchanged levels of testosterone, progesterone and FSH. Patients with luminal B and TNBC subtypes with progression in 6-12 months did not show significant changes in prolactin and cortisol levels after two chemotherapy cycles, compared with the values before treatment. Conclusions: A decrease in blood levels of prolactin and cortisol after two chemotherapy cycles is an indicator of a long-term remission in patients with breast cancer.
WNT/β–catenin pathway activation correlates with the increase of tumor-associated macrophages in triple negative breast cancer (TNBC).
Authors: Timperi Eleonora , Ye Mengliang , Dubois Thierry , Meseure Didier , Salomon Anne Vincent- , Romano Emanuela 
Published: May 2020

e12564 Background: Triple negative breast cancer (TNBC) occurs in about 20% of all breast carcinomas. Because only a fraction of TNBCs responding to immune checkpoint blockade show a pre-existing T cell-inflamed tumor microenvironment (TME), it is critical to understand the mechanisms of T-cell exclusion. Tumor-cell intrinsic activation of the WNT/β–catenin pathway, overexpressed in 30% of human breast cancers, is linked to a T-cell excluded TME. In β–cateninhigh TNBC, however, the quality of the myeloid compartment has not been evaluated. Methods: A total of seventy-five, early-stage, untreated, TNBC patients was assessed (patient cohorts approved by IRB). β–catenin expression was detected by IHC and scored as high, intermediate, and low. The presence of T cells, tumor-associated macrophages (TAMs) and LAMP-expressing dendritic cells (LAMP+ DCs) was assessed by IHC using aCD3, aCD68, aCD163, and aLAMP, respectively. Public TNBC datasets TCGA (N = 157) and METABRIC (N = 319) were interrogated for correlations between β–catenin- and immune-associated genes. Results: Three patient groups (N = 25/group) were identified according to the negative, medium and high intracellular expression of β–catenin. As opposed to β–cateninlow TNBC, the β–cateninhigh group displayed significantly lower CD3+ T cells (median 5% ±7.37 SD vs median 30% ± 18.28 SD, p < 0.0001) and LAMP+ DCs (median 1% ± 2.515 SD vs median 10% ± 7.038 SD, p < 0.0001). The β–cateninlow group was enriched in lymphocyte-predominant TNBC. For the first time, we show that the immune-suppressive, CD68+CD163+ TAMs were strongly accumulated in the β–cateninhigh group (median 20% ± 12.20 SD vs median 5% ± 6.831 SD, p < 0.0001). The interrogation of the public TNBC datasets TCGA and METABRIC confirmed that – after patient statification according to the expression level of a WNT/β–catenin gene-signature (i.e. MMP7, SFRP1, WNT10A, WNT16, WNT9B) – multiple TAM-associated genes – identified by our group in a single-cell RNAseq dataset – were strongly upregulated in WNT/β–cateninhigh signature, highlighting the role of the WNT/β–catenin signaling pathway not only in T-cell exclusion but also in selective TAM accumulation. Conclusions: Immune-suppressive TAMs are accumulated in β–cateninhigh, T-cell excluded TNBCs emphasizing the importance of tumor-intrinsic factors in shaping the quality of the immune infiltrate.
Breast cancer: The Indian scenario.
Authors: Gogia Ajay , Deo Svs , Sharma Dayanand , Mathur Sandeep 
Published: May 2020

e12567 Background: This study was undertaken to evaluate the clinic-pathological characteristics and outcome of patients with female breast cancer at I.R.C.H, AIIMS, New Delhi, one of the largest tertiary-care cancer center in India. Methods: This ambispective study included patients with breast cancer in females, registered at our institute from January 1st, 2014 to December 31st, 2018.We retrieved data from prospectively maintained clinical case records. Results: We included 997 patients with median age of 47.5 years (21–90) The TNM (AJCC-7th edition) stage distribution was stage I, 40 (4.01%); stage II, 326 (32.70%); stage III, 419 (42.02%); and stage IV, 212 (21.26%). The median tumour diameter was 5 cm. Infiltrating ductal carcinoma (96%) was the most common histologic subtype. Fifty eight percent of cases were positive for ER or/ and PR whereas 30.89% patients were HER2/neu positive. Triple negativity was found in 29.88 % of cases. Patients underwent breast conserving surgery in 28.2% of cases, 41.7% were received neo-adjuvant chemotherapy and 9.5 % of patients offered palliative chemotherapy. The pathological complete response was seen in 20.5% of cases. Loco-regional recurrence occurred in 2.8%, and 23.2% of patients developed distant metastases. The discordance of receptor was present in 20.5% for ER, 25.1% for PR, and 15 % for HER2/neu on re-biopsy at the time of relapse . Only 37.83% of the eligible patients received trastuzumab upfront. For non- metastatic group, the median time of relapse was 36 months, 3 year relapse free survival (RFS) was 73.5% and overall survival (OS) was 82.1% . Clinical stage(stage III), triple negativity and HER2 neu positivity were associated inferior RFS however pathological node involvement (HR 1.4, 95% CI 1.01–2.18, p = 0.01) and triple negativity (HR 1.9, 95% CI 1.36–2.90, p = 0.001) were associated with poor OS . For metastatic group, the median time of progression was 18 months and 3 year progression free survival (PFS) was 35% and OS was 20%. More than 2 sites of metastasis, upfront brain metastasis, triple negativity, and poor performance status (ECOG III/IV) were associated with inferior survival. Conclusions: This is one of the largest comprehensive data from a single center. Majority of our patients are younger in age, advance in stage, aggressive in biology and unaffordability of targeted therapy on eligible patients might lead to poor overall outcome. Triple negativity is found in around 30% of cases and associated with poor survival.
Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer.
Authors: Ma Ji , Sun Lingqi , Liu Ying , Ren Hui , Shen Yali , Bi Feng , Zhang Tao , Wang Xin 
Published: May 2020

e12575 Background: The aim was to evaluate the changes of 16S rDNA sequencing and LC-MS metabolomics in breast cancer and explore the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii. Methods: We performed the 16S rDNA sequencing of gut bacteria and the LC-MS metabolomics analysis of blood samples in 25 breast cancer patients and 25 benign breast disease controls. Correlation analysis of significant flora and metabolites were processed, including correlation coefficient calculation, matrix heat map analysis, cluster analysis, correlation network analysis, and scatter plot analysis. We screened for intestinal flora that may participate in breast cancer development and try to test and verify. CCK-8, apoptosis and transwell assays were explored to detect the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii. Western blot was used to analyze the changes of IL-6/STAT3 pathway by Faecalibacterium prausnitzii. Results: Total 49 significantly different flora and 26 different metabolites were screened between two groups, and the correlation was calculated. Relative abudance of Firmicutes and Bacteroidetes were decreased, while relative abundance of verrucomicrobla, proteobacteria and actinobacteria was increased in breast cancer group. Differentially expressed metabolites were mainly enriched in pathways such as linoleic acid metabolism, retrograde endocannabinoid signaling, biosynthesis of unsaturated fatty acids, choline metabolism in cancer and arachidonic acid metabolism. Lipid upregulation was found in breast cancer patients, especially phosphorocholine. The abundance of Faecalibacterium was reduced in breast cancer patients, which was negatively correlated with various phosphorylcholines. Moreover, Faecalibacterium prausnitzii, the most well-known species in Faecalibacterium genus, could inhibit the secretion of IL-6 and the phosphorylation of JAK2/STAT3 in breast cancer cells. Faecalibacterium prausnitzii also suppressed the proliferation and invasion and promoted the apoptosis of breast cancer cells, while these effects disappeared after adding recombinant human IL-6. Conclusions: Flora-metabolites combined with the flora-bacteria (such as Faecalibacterium combined with phosphorocholine) might a new detection method for breast cancer. Faecalibacterium may be helpful for prevention of breast cancer. Faecalibacterium prausnitzii suppresses the growth of breast cancer cells through inhibition of IL-6/STAT3 pathway.
E2F cell cycle pathway score as a predictive biomarker of ER+/HER2- breast cancer response to neoadjuvant chemotherapy.
Authors: Oshi Masanori , Tokumaru Yoshihisa , Katsuta Eriko , Yan Li , Endo Itaru , Takabe Kazuaki 
Published: May 2020

e12593 Background: Although the survival rate of patients diagnosed with breast cancer has greatly improved over the last decades, the metastatic stage of the disease remains incurable. Estrogen receptor positive (ER+)/human receptor 2 negative (HER2-) breast cancers accounts for approximately 70% of metastatic breast cancers and, it is responsible for most of the deaths from the disease. Another issue of ER+/HER2- breast cancer is its poor response to neoadjuvant chemotherapy (NAC). Recently, several clinical trials have shown that endocrine therapy plus FDA-approved cyclin-dependent kinases (CDK) 4/6 inhibitors have improved the treatment response to patients with advanced ER+/HER2 breast. The CDK 4/6 is an important E2F-related factor. Therefore, we hypothesized that E2F pathway is predictive biomarker for treatment response of ER+/HER2- breast cancer. Methods: METABRIC dataset was used for training cohort. And TCGA breast cancer as well as four neoadjuvant therapeutic cohorts were used as validation cohort. The E2F pathway score was calculated by Gene Set Variant Analysis (GSVA). Results: Tumors with high E2F pathway score enriched cell proliferation and cell cycle pathway related gene sets (G2M, MYC v1, and v2, MITOTIC, MTORC1, PI3K AKT MTOR, and DNA repair; FDR < 0.001). The high E2F pathway score was significantly associated with TNBC and HER2+ (p < 0.001), which are known to be clinically aggressive, and advanced stage (p < 0.001) and high grade (p < 0.001). The score also correlated with copy mutation (r = 0.605, p < 0.01). The patients, who had early recurrence before 5 years, had significantly high score rather than non-recurrence patients (p < 0.001). Moreover, these results were validated in TCGA cohort. The high E2F pathway score group had a higher pCR rate than the low score group with ER+/HER2- breast cancer (p < 0.001). Interestingly, the tumors in high score group expressed higher CDK pathway related molecules compared to low score group. Conclusions: The E2F pathway score was found to be a predictive biomarker for neoadjuvant chemotherapy in ER+/HER2- breast cancer patients.
Neoadjuvant endocrine therapy versus neoadjuvant chemotherapy in young women with breast cancer: Prognosis and axillary node surgery.
Authors: Gwark Sung-chan , Ahn Sei Hyun , Ahn Jin-Hee , Jung Kyung Hae , Kim Sung-Bae , Gong Gyungyub , Lee Sae Byul , Kim Jisun , Chung Il Yong , Ko Beom Seok , Lee jong Won , Son Byung Ho , Kim Seon-Ok , Kim Hee Jeong 
Published: May 2020

e12626 Background: We aimed to evaluate patient-reported outcomes (PROs) in the NEST phase III trial, in which neoadjuvant endocrine therapy (NET) compared to conventional neoadjuvant chemotherapy (NCT) for hormone-responsive lymph node-positive premenopausal breast cancer. Methods: Premenopausal women with estrogen receptor (ER)-positive, HER2-negative, and lymph node-positive premenopausal breast cancer patients were enrolled. Patients were randomized to either 24 weeks of neoadjuvant chemotherapy with adriamycin plus cyclophosphamide (AC) followed by taxane (T) or neoadjuvant endocrine therapy with zoladex and tamoxifen. PROs were assessed at day 1 (baseline) and at the end of treatment, using the breast cancer module of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 23 (EORTC QLQ BR23). ClinicalTrials.gov: NCT01622361. Results: 187 patients were randomly assigned to chemotherapy (n = 95) or endocrine therapy (n = 92), and 174 patients completed the 24 weeks of neoadjuvant treatment period (n = 87, both). Baseline scores were similar between arms. No statistically significant between-treatment differences were observed for the function scales including body image, sexual functioning, and sexual enjoyment although endocrine treatment showed significant improvement in future perspective (HR = 8.3, 95% CI:1.72-18.38; P= 0.021). Even though no alopecia was reported in NET group, no statistically significant difference between both arms in the “upset by hair loss” was observed, in which NET group showed even worse score. Conclusions: Patients who received NET had significant improvement in a future perspective, however, a similar emotional negative impact on hair loss was observed compared with NCT despite no reported alopecia. Key words: breast cancer, patient-reported outcomes, quality of life, hair loss, EORTC QLQ-BR 23. Clinical trial information: NCT01622361.
21-gene recurrence score assay as a predictor of pathological response in neoadjuvant chemotherapy administration for ER-positive/HER2-negative early-stage breast cancer.
Authors: Murillo Serafin Morales , Gasol Cudós Ariadna , Rodriguez Alvaro , Canosa Morales Carles , Olivé Jordi Melé , Vilardell Felip , Sanchez Guzman Douglas 
Published: May 2020

e12630 Background: Neoadjuvant chemotherapy (NAC) is an optimal option in early breast cancer, but in ER-positive/HER2-negative (luminal) is still controversial, although a survival benefit has recently been observed when a histological response by symmands method type 0 or I is achieved. The 21-Gene recurrence score assay (Oncotype DX) is a validated test to assess the survival benefit of adjuvant chemotherapy in these patients but its role in neoadjuvant setting is not yet well established unknown. We analyze the correlation between Oncotype DX Recurrence Score result and the pathological response assessed by symmands method. Methods: We analyzed a prospective cohort of 63 early luminal breast cancer patients who received NAC after performing an Oncotype DX test. Patients with an Oncotype DX Recurrence Score result lower 11 were excluded. The median age was 54 years (31-84), initial tumor size was 37 mm (12 -97), 41 patients (65%) had initial nodal involvement and the median Ki67 index was 34% (8 – 85). Results: An Oncotype DX results inferior or equal to 25 (considered as a limited benefit of chemotherapy treatment) was observed in 25 patients (40%) and a Recurrence Score higher than 25 in 38 (60%). Pathological response type 0 was achieved in 5 patients (8%) and type I in 16 (25%). A strong correlation between pathological response type 0 and I and Recurrence Score result in the univariate and multivariate analysis (OR 0,946 p:0,023) was found. We have performed a threshold analysis finding the Oncotype DX the most significant predictor of pathological response (AUC:0,75 p:0,0 01 ) compared to Ki67 (AUC:0,61 p:171), Estrogen receptor (AUC:0,41 p:0,21) and initial tumor size (AUC:0,671 p:0,028). All the patients who achieved a complete pathological response had a Recurrence Score result ≥ 26. Conclusions: The Oncotype DX Recurrence Score could be a useful tool to select early breast cancer patients who will benefit from neoadjuvant chemotherapy. Oncotype DX is the most significant predictor variable of pathological response and patients with a Recurrence Score of 25 or greater are five times more likely to obtain a histological response type 0-1 (OR: 5,3 p < 0,016). In our series the Oncotype DX test reaches the highest rate of complete pathological responses in this group of patients.
Perfusion kinetics from clinical DCE mris increase the accuracy of predictions of tumor response to chemotherapy.
Authors: Cole John A , Peterson Joseph R , Earnest Tyler M , Hallock Micahel J , Pfeiffer John R , Pandey Tushar , Braun Eduardo 
Published: May 2020

e12651 Background: Nutrient and drug penetration into any solid tumor are critical determinants of the tumor's response to treatment. They depend on both the density of microvasculature within the tumor microenvironment, as well as the exchange rates of nutrients between the microvasculature and the extracellular space. But these parameters are heterogenous, varying considerably from location to location within the tumor and surrounding tissues. The Toft's model and its analogues date back to the early 1990s, and have been used to estimate vascular density, exchange rates, and extracellular-extravascular volume in a spatially-resolved manner using dynamic contrast enhaced (DCE) MRI's. Unfortunately, accurately extracting kinetic parameters from a DCE time-series requires the images to have a time-resolution of just a few seconds, which is rarely done in clinical practice. Methods: We employ a custom designed parallel algorithm to fit DCE MRI data to an exactly-solved ODE model of tissue perfusion kinetics. Results: Here we describe a simplified model of tissue perfusion that can be fit to DCE time traces with temporal resolutions of 90 seconds or more. We show that for many breast tumors, the vascular density and tissue-vascular exchange rate are such that they give rise to a halo of fast-perfusing tissue on the tumor periphery, and slower-perfusing tissue inside. We then use this model as part of a more comprehensive tumor simulation methodology to predict how different patients will respond to neoadjuvant chemotherapy (NACT). We find that the incorporation of our microvascular model gives rise to significantly more accurate predictions of post-treatment tumor volume. Conclusions: Performing perfusion kinetics analyses on clinical MRIs is both challenging, but critical for accurately predicting how a patient will respond to treatment. Our model, which relaxes the requirement for fine DCE temporal resolution, allows for these analyses to be performed on a larger swath of patients without the need for small volumes of interest, or ultra-fast MRI techniques. Moreover, when used within a broader tumor-modeling framework, our model increases the accuracy of predictions of tumor response to NACT.
Pathological outcomes of HER2-positive early breast cancer patients treated with neoadjuvant trastuzumab or dual anti-HER2 therapy and carboplatin with docetaxel: A Maria Sklodowska-Curie National Research Institute of Oncology experience.
Authors: Jagiello-Gruszfeld Agnieszka I. , Lemanska Izabela , Sienkiewicz Renata , Szombara Ewa , Dubianski Roman , Brewczynska Elzbieta , Pogoda Katarzyna , Konieczna Aleksandra , Kunkiel Michal , Majstrak-Hulewska Anna , Olszewski Wojciech P , Niwinska Anna , Nowecki Zbigniew 
Published: May 2020

e12655 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) for breast cancer predicts the risk of recurrence and increasingly may indicate the need for additional therapy postoperatively. Methods: A retrospective analysis was performed in two cohorts of patients (pts) treated with docetaxel, trastuzumab and carboplatin (TCH) or with docetaxel, carboplatin and dual blockade (TCH-P) in the neoadjuvant setting in patients with early breast cancer (tumor size < 50 mm and > 10 mm and cN0 or cN1) in our Clinic, and who had definitive surgery was conducted. Demographic data, size, grade, tumor type, receptor status prior to neoadjuvant treatment, pathological complete response (pCR) rates, and adverse effects were analyzed. The pCR was defined as ypT0 ypN0. Results: Patient in cohort A (n = 58) received TCH x 6 cycles and in cohort B (n = 25) TCH-P x 6 cycles. Median age was 51 (range 23 to 76 years) in cohort A and 46 (range: 30-68) in cohort B. In cohort A 37 (64%) of pts was HR-positive, in cohort B only 9 (36%) pts . The most common adverse events in both groups were neutropenia, diarrhea, chemotherapy induced polyneuropathy and febrile neutropenia. There are no significant differences in the frequency of adverse events in two cohorts. There was no symptomatic heart failure, but 6 pts (10%) in cohort A and 5 pts (16%) in cohort B had > 10% asymptomatic decrease in LVEF. All patients were evaluable for pCR. Higher rates of pCR were achieved in the HER2pos/HRneg pts: 66% (n = 14) in cohort A, and 87% (n = 14) in cohort B. In group HER2pos/HRpos pts, the pCR rate was 48% (n = 18) vs 55% (n = 5) respectively. Conclusions: In HER2positive early breast cancer, a dual blockade (trastuzumab and pertuzumab) together with carboplatin and docetaxel neoadjuvant chemotherapy achieved higher rates of pCR ( 76%) compared with pts treated with trastuzumab, carboplatin and docetaxel (56%). However, a much higher percentage of pCR was observed in the group of patients with non-luminal cancers, who received a double blockade (87% vs 66%).