bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change in HER2 status after neoadjuvant chemotherapy (NAC) with trastuzumab and pertuzumab (HP) in patients with HER2-positive early-stage breast cancer.
Authors: Ferraro Emanuela , Razavi Pedram , Chandarlapaty Sarat , Modi Shanu , Wen Hannah Yong , Brogi Edi , Norton Larry , Robson Mark E. , Dang Chau T. 
Published: June 2021

e12614 Background: Combination of HP with NAC in the neoadjuvant setting leads to an high rate of pathological complete response (pCR) in patients with stage II-III HER2+ breast cancer (BC). The rate of change in HER2-status after NAC reported in literature is between 10-30%, although NAC comprises a various regimens, and the clinical significance of this phenomenon is unclear. Methods: We extracted data on patients with HER2+ BC treated with NAC and HP between September 1, 2013 to November 1, 2019. Only patients with internally verified HER2 status at our center were enrolled. The rate of pCR (ypT0/is ypN0) and the change in HER2 status on residual disease from baseline were evaluated. We used standard definition of HER2 status based on ASCO/CAP guidelines 2018. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+, FISH non-amplified. Results: Overall, 130 pts were identified. All patients received dose-dense AC-THP, except for 13 patients who received TCHP or other HP-based regimens. The pCR was achieved in 77/130 (59%) of patients and 53/130 (41%) had residual disease. Among 53 patients with residual disease, HER2 status was analyzed in 25 patients and was pending on the remaining patients. In the 25 analyzed patients, 13 had HER2-loss in residual disease. In 4/13 patients, HER2 expression was lost (IHC 0); in 9/13 patients, HER2-low profile was found (IHC 1+ in 6 patients, and IHC 2+, FISH non-amplified in 3). Details on HER2 status change are described in the table below. Conversely, 12/25 had concordant HER2 status after NAC. Conclusions: At single center, the change in HER2 status after NAC with HP appeared frequent. Pathological review of additional cases is ongoing. The clinical significance is still unclear but may open the possibility to investigate tailored approach in post-neoadjuvant setting based on the biological profile of residual disease. [Table: see text]
Paclitaxel versus docetaxel-based neoadjuvant chemotherapy and risk of lymphedema in breast cancer patients.
Authors: Zhu Yirong , Refaat Abdelrhman Tamer , Ho Yvonne D. , Thomas Tarita , Small William , Godellas Constantine , Vaince Faaiza , Mai Hanh P. 
Published: June 2021

e12620 Background: Neoadjuvant chemotherapy (NAC) is commonly utilized in women with locally advanced breast cancer, usually followed by surgery and radiation therapy (RT). Many studies aimed to address the risk factors contributing to a higher incidence of lymphedema in patients with breast cancer. Our group previously reported the extent of surgery increases the risk of lymphedema. Adjuvant chemotherapy with taxane-based regimens are associated with an increased risk of lymphedema likely due an increase in interstitial extracellular fluid volume therefore resulting in fluid retention. This study aims to directly compare and characterize the risk of lymphedema in patients receiving paclitaxel versus docetaxel-based NAC. Methods: This is a retrospective study approved by our institutional review board. The study included women with breast cancer treated consecutively at our institution with taxane-based NAC followed by surgery and RT from 2006 to 2018. Patients and tumor characteristics including age, race, body mass index (BMI), clinical stage, hormone receptor, HER2 status, type of surgery, RT techniques, and type of NAC (Paclitaxel versus Docetaxel), and its association to risk of lymphedema were analyzed using univariable and multivariable binary logic regression tests. Lymphedema was assessed before RT and at follow up visits, and was identified by >2.0-cm increase in arm circumference, or >10% increase in limb volume, or new self-reported lymphedema symptoms. Results: A total of 263 patients treated with either paclitaxel or docetaxel-based NAC were identified and analyzed. At a median follow up of 28.4 months (range 3.5-158.7 months). 26.2% (69/263) of patients developed lymphedema. On a multivariable analysis, patients who underwent axillary lymph node dissection (ALND) had a significantly higher rate of lymphedema (42.6%) compared to those who had only a sentinel lymph node biopsy (SLNB, 10.5%, p<0.05). Regardless of the type of surgery, there was no significant difference in rates of lymphedema between patients who received paclitaxel versus docetaxel-based NAC (28.7% vs 21.3%). However, among high-risk patients who underwent mastectomy with ALND, NAC with Paclitaxel was associated with a significantly higher rate of lymphedema compared to docetaxel (56.8% vs 22.7%, RR 2.50, p<0.05). Conclusions: This represents one of the largest studies examining the impact of taxane-based NAC on the risk of lymphedema in women with breast cancer. In this study, paclitaxel-based NAC was associated with a significantly higher risk of lymphedema in women who underwent mastectomy and ALND compared to docetaxel based chemotherapy. A larger, balanced, prospective study is warranted to verify this previously unidentified lymphedema risk from paclitaxel and guide individualized NAC decision.
Baseline neutrophil-to-lymphocyte ratio and absolute lymphocyte count in patients with HER2-negative breast cancer treated with eribulin may predict overall survival.
Authors: Maeda Shigeto , Anan Keisei , Koga Kenichiro , Kuba Sayaka , Yano Hiroshi , Kai Yuichiro , Nishimura Reiki , Toh Uhi , Yamaguchi Miki , Mashino Kohjiro , Mitsuyama Shoshu , Tamura Kazuo , Tanaka Toshihiro , Iwase Hirotaka 
Published: June 2021

e13005 Background: In Japan, eribulin has been approved for inoperative or recurrent breast cancer, following treatment with an anthracyclines and a taxanes. We reported the efficacy and safety of eribulin as a first-line to third-line treatment in patients with advanced/metastatic breast cancer (MBC) previously treated with anthracylinsanthracyclines and taxanes (Breast 2017). Briefly, the main inclusion criteria were as follows: no history of eribulin administration; an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2,; human epidermal growth factor receptor 2 (HER2)-negative,; 20–75 years; ≥4 weeks from the last dose of chemotherapy, or ≥2 weeks from the last dosing of endocrine or radiation therapy; measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1; sufficient organ function; life expectancy of ≥3 months; and no significant abnormalities on electrocardiogram. Patients in this clinical trial were enrolled between December 1, 2011, and November 30, 2013. Eribulin was administered intravenously at a dose of 1.4 mg/m2 during a 2-5 min infusion on days 1 and 8 every 3 weeks. In contrast, baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) were reported to predict progression-free survival (PFS) or overall survival (OS). However, these reports were mainly retrospective analysis. Therefore, retrospective evaluation of NLR/ALC in a prospective clinical trial is important to understand the association between NLR/ALC and OS/PFS. Methods: Of 47 prospectively enrolled patients in a previous trial, 45 patients were retrospectively evaluated for baseline NLR/ACL and at the time of 3 cycles of eribulin. The association between NLR/ALC and OS/PFS was also were analyzed for association with OS/PFS. The Kaplan-Meier method was used to estimate the OS/PFS distribution. The cut-off values for baseline NLR and ALC were set at 3 and 1500 /ul, respectively. Results: The median OS of patients with a baseline NLR < 3 was significantly longer than that of patients with a baseline NLR ≥ ≧3 (769 days vs. 409 days; log-rank test p = 0.0333). The median OS of patients with a baseline ALC ≥ ≧1500 was also significantly longer than that of patients with a baseline ALC < 1500 (964 days vs.vs 427 days; log-rank test p = 0.0425). Association between baseline NLR/ALC and PFS were not seen, and also association between at the time of 3 cycles of NLR/ALC and OS/PFS were not seen neither. Conclusions: Baseline NLR and ALC in the patients with HER2- negative breast cancer who plan to treat eribulin may predict overall survival. Clinical trial information: UMIN000007121.
Analysis of circulating tumor DNA identifies homologous recombination repair molecular features of Chinese breast cancer.
Authors: Li Mingwei , Yang Tongtong , Wang Huina , Lou Feng , Cao Shanbo 
Published: June 2021

e13006 Background: Breast cancer (BC) is the most common cancer in women world-wide. Assessments of genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of BC. Alterations in homologous recombination repair (HRR), are a determinant of sensitivity to platinum chemotherapy and poly (ADP-ribose) polymerase inhibitors (PARPi) in BC. However, as far as we known, most of HRR genes, except BRCA1/2, have not yet been fully understood to date. In this study, we aimed to elucidate the comprehensive HRR genetic alteration profile of breast tumors among Chinese patients by ctDNA analysis. Methods: Plasma ctDNA from 259 patients with BC were deeply sequenced via next-generation sequencing (NGS) techniques using AcornMed Biotechnology for 808 genes panel. Molecular profiles were reviewed to identify somatic and germline pathogenic mutations in the 14 HRR genes ( ATM, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, PALB2, RAD51B, RAD51C, RAD51D, RAD54L, CDK12, and BARD1) . Results: At our institution, 259 patients underwent NGS analysis of BC specimens. The median age was 46 (range from 31 to 79). Based on the analysis of the genetic alteration profile from our cohort, at least one of the HRR genes was observed from 29.34% of the tumor samples, with BRCA1 (8.11%), BRCA2 (5.79%), RAD51C (5.02%), CDK12 (4.63%), CHEK2 (1.93%), ATM (1.16%), and BARD1 (1.16%) as the most commonly altered genes. As compared with MSKCC dataset (Table), genetic alterations detected from our cohort affected genes involved in HRR (29.34% vs. 14.03%, P＜0.0001) pathways, with statistically different genetic alteration rates. Moreover, BRCA1/2, RAD51C, CDK12 and CHEK2 mutations exhibited higher mutation rates, whereas ATM, BRIP1 and PALB2 mutations presented a lower mutation rate in Chinese patients with breast cancer (P＜0.05). Conclusions: CtDNA can characterize the mutational feature of HRR in BC. our study contributes to the understanding of the HRR pathways and specific genetic alterations harbored by Chinese patients with BC that could potentially be developed as markers of treatment response to targeted therapeutics. Ref: Razavi P, Chang MT, Xu GT, et al. The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers. Cancer Cell. 2018 Sep 10;34(3):427-438.e6. doi: 10.1016/j.ccell.2018.08.008.[Table: see text]
TDM-1 efficacy in trastuzumab-pertuzumab pre-treated HER2 positive metastatic breast cancer patients: A meta-analysis.
Authors: Omarini Claudia , Piacentini Federico , Sperduti Isabella , Cerma Krisida , Barbolini Monica , Canino Fabio , Nasso Cecilia , Dominici Massimo , Moscetti Luca 
Published: June 2021

e13010 Background: Based on the results reported in Emilia trial population, current guidelines consider TDM-1 the standard second-line therapy for HER2 positive metastatic breast cancer (MBC) patients. Despite that, there are no prospective studies supporting the efficacy of TDM-1 following trastuzumab (T) + pertuzumab (P) and taxane first-line treatment. Currently, only real-world data have investigated this sequence with controversial results Methods: We performed a meta-analysis of the available real world data to determine the efficacy of TDM-1 after first-line TP in HER2 positive MBC patients. We used a random-effect model to find differences in the rate of 1-year progression free survival (PFS) between TP pre-treated population and the phase III Emilia trial (T pre-treated population). Results: Seven studies were eligible, in three of them data were from sub-group population analysis. The meta-analysis showed a combined 1-years PFS risk difference for TDM-1 efficacy after TP in second or more lines of -0.122, with lower and upper limits of -0.253 and 0.010, respectively (p=0.07) , with low heterogeneity among studies (I2 < 0.0001, p =0.836). Considering the four studies on TDM-1 in second-line setting, 1-years PFS risk was -0.034 (95% CI -0.207 – 0,139; p=0.701) (I2 < 0.0001, p =0.91). Conclusions: Results from the meta-analysis show that the efficacy of TDM-1 after TP double-block seems to be similar to the previously reported in Emilia trial. In the second line setting, available data are not mature enough to confirm TDM-1 efficacy in TP pre-treated population. Currently, TP pretreated patients should receive TDM-1 as indicated in the guidelines.
Pre-clinical development of an anti-cancer drug ENZ302, a promising candidate for multiple cancer therapeutics.
Authors: Chakraborty Arindam , Banerjee Abir , Gadgil Himanshu 
Published: June 2021

e13053 Background: Vernonia cinerea extract has been known to be used for various haematological disorders including cancer. In the current study, using state-of-the-art extraction and bioanalytical tools we have identified an active compound having anti-tumor properties from the same plant Vernonia cinerea. The crude extract of Vernonia cinerea as well as the active molecule obtained through the chemical route (ENZ302) showed anti-tumor activity against various cancer models including CML, AML, ALL, HER2+ breast cancer, colon cancer, etc. Methods: Various methods including RP-HPLC, XRD, NMR, IR, cell based assay and LC-MS were used to elucidate the molecular structure of ENZ302. MTD, DRF, PK, and Xenograft study etc were carried out in murine model during the preclinical development of ENZ302. Results: ENZ302 resulted significant cytotoxic effect within 8 hrs of treatment in TNBC (Triple Negative Breast Cancer) model, MDA-MB-468 cells when compared with a known inhibitor Lapatinib. However, ENZ302 treatment in primary cells demonstrates no anti-proliferation activity, indicating the specificity of it’s mode of action. Interestingly, a dose-dependent decrease in tumor volumes was observed for ENZ302 in a xenograft model of TNBC while administered orally. ENZ302 did not cause any adverse changes even at 2gm/Kg dose, indicating the safety of the compound. Although a single-dose PK study showed that ENZ302 has a half-life of ̃40 mins, however, in vitro metabolism of the compound in mouse, rat, dog, and human hepatocytes/microsomes showed the molecule is stable in hepatocyte with very low clearance in microsomes (half-life > 30 min), indicating most of the clearance occurring through the kidney. Conclusions: Our preliminary data suggest that ENZ302 is a specific tyrosine kinase (e.g. Src) inhibitor and a promising therapeutic agent against several cancers. A comprehensive proteomic analysis is ongoing to understand the mechanism of action of ENZ302 that makes it effective against several cancers. The discovery of ENZ302 holds ample opportunities to develop a safe and efficacious treatment regimen against several cancers including TNBC.
The common gamma-chain cytokines IL-2, IL-7 and IL-15 impact on proliferation of lymphocytes in vitro in breast cancer patients.
Authors: Timofeeva Sofia V. , Sitkovskaya Anastasia O. , Zlatnik Elena Yu. , Filippova Svetlana Yu. , Shamova Tatiana V. , Mezhevova Irina V. , Novikova Inna A. , Vashchenko Larisa N. , Kechedzhieva Emma E. , Dashkova Irina R. , Ausheva Tatiana V. , Andreyko Elena A. , Saforyan Natalya S. , Kit Oleg I. 
Published: June 2021

e13060 Background: Monotherapy with low doses of cytokines does not provide significant therapeutic results, while treatment with high doses leads to a number of side effects, for example, cytokine release syndrome, etc. Therefore, it is necessary to study the effect of cytokines on immune cells which are involved in the regulation of pro- and antitumor immune response. Thus, the aim of this study was to analyze the dynamics in the proliferation of the total fraction of lymphocytes after expansion and exposure to γc-cytokines: IL-2, IL-7 and IL-15 and their combinations in vitro in patients with diagnosed breast cancer. Methods: The study included 10 patients with locally advanced stage I-III breast cancer. Peripheral blood mononuclear cells (PBMC, ficoll-hypaque) were used as material. After density separation the cells were cultured at a dose of 500 thousand cells / ml in 6-well plates (Biofil, China) in RPMI 1640 (Gibco, USA) supplemented with 10% FBS (HyClone, USA) at 37° C, 5% CO2. Expansion of lymphocytes was performed by kit with anti-biotin magnetic particles MACSiBead to CD2, CD3 and CD28 (Miltenyi Biotec, Germany), according to the manufacturer's protocol. Stimulation of lymphocyte proliferation was performed on days 4, 8 and 12 by introducing recombinant cytokines - IL-2, IL-7, IL-15 (Miltenyi Biotec, Germany) and their combinations. Cytokines were introduced at a concentration of 40 ng / ml each in the following variants: IL-2; IL-2 / IL-15; IL-2 / IL-15 / IL-7; IL-15; IL-15 / IL-7. Plates with cell suspension were cultured at 37 ° C, 5% CO2 for 15 days. Results: The data obtained on the 11th day of incubation demonstrated statistically significant differences in cell viability in samples with the addition of interleukin IL-7 / IL-15 combination (778%) compared to control samples by 1.5 times (p < 0.05). The proportion of lymphocytes in samples with the addition of only IL-15 (702%) and IL-7 / IL-15 (756%) combination was 1.47 and 1.6 times higher, respectively, compared with the control (p < 0.05) at the 12th day of co-cultivation. Conclusions: Stimulation of lymphocyte proliferation by the IL-7 / IL-15 combination results in a high frequency of viable cell production. Despite the only culture stage, the results of the study may be important for optimizing the use of γc-cytokines in the treatment of patients with breast cancer.
Efficacy of everolimus-containing chemotherapy in HER2 negative metastatic breast cancer patients with PI3K/AKT/mTOR mutations: A retrospective study.
Authors: Wang Rong , Wang Xiaojia , Chen Zhan-hong , Niu Jin , Huang Yuan , Pan Jiani , Ye Weiwu , Cao Wenming 
Published: June 2021

e13069 Background: The PI3K/AKT/mTOR pathway is frequently altered in breast cancer. Everolimus is a selective inhibitor of mammalian target of Rapamycin (mTOR).The benefit of everolimus in metastatic breast cancer patients with PI3K/AKT/mTOR mutations remains unclear, especially in TNBC patients. Our study aimed to investigate the efficacy of the everolimus-containing chemotherapy in metastatic breast cancer patients with PI3K/AKT/mTOR mutations. Methods: 13 cases of HER2- metastatic breast cancer with PI3K/AKT/mTOR mutations treated with everolimus-containing chemotherapy were analyzed. The genetic profile in PI3K/AKT/mTOR pathway was studied. Results: Overall, 4 cases were hormone receptor (HR) positive and 9 were TNBC. 7 patients only had PIK3CA mutations, 1 patient had only PIK3R1 mutations, and 5 patients had other mutations in the pathway in addition to PIK3CA, including PTEN, PIK3CB, CTNNB1, FGFR1 and TSC2. 5 cases were treated as first or second line chemotherapy, and 8 were as third line or above. The ORR (CR+PR) was 38.5% (5/13), and DCR (CR+PR+SD) was 84.6% (11/13), including 5 cases of PR, 6 cases of SD, and 2 cases of PD. The median PFS was 5.8 months (95% CI 3.7-9.7), and the median OS was 14.3 months (95% CI 6.47-null). However, the ORR of TNBC patients was higher than that of HR-positive, which were 44.4% (4/9) and 25% (1/4), respectively ( p = 0.070). The mPFS was also longer than that of HR-positive with 5.8 months versus 1.7 months, as well as the mOS with 14.3 versus 3.8 months. We also found that the patients carrying other mutations besides PIK3CA in the PI3K/AKT/mTOR pathway had a longer PFS compared to the patients without other mutations, which was 9.7 months and 4.3 months respectively ( p = 0.272). And the DCR of the two groups were 100% and 75% respectively ( p = 0.451). Conclusions: We found that everolimus-containing chemotherapy was effective in the treatment of HER2- metastatic breast cancer with PI3K/AKT/mTOR pathway activation. TNBC patients had a trend of longer mPFS than HR+ patients. And the patients carrying other mutations besides PIK3CA in the PI3K/AKT/mTOR pathway have a trend of longer PFS and higher DCR compared to the patients without other mutations. However, trails with larger samples are needed for further verification.
Optimizing chair time in infusion centers using intravenous cetirizine premedication for the prevention of hypersensitivity infusion reactions.
Authors: Peguero Julio Antonio , Ayad Ahmed , Young-Wesenberg Stacia , Yang Teresa , North Janine , Joseph-Ridge Nancy 
Published: June 2021

e13508 Background: Oncology infusion centers are increasingly focused on improving operational efficiencies and patient satisfaction, while maintaining quality care. One key component is optimizing chair time, which has been especially important for patient safety during the COVID-19 pandemic to reduce risk of transmission. Many infusions require antihistamine premedication to reduce the risk of hypersensitivity infusion reactions (IRs). The two IV options are IV diphenhydramine and IV cetirizine, which have a quicker onset than oral options and can be administered IV push. In treating acute urticaria, IV cetirizine was shown to be comparable to IV diphenhydramine, with fewer side effects, and it may be effective for preventing IRs with improved chair time. Methods: A randomized, double-blind phase 2 study evaluating premedication with single dose IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 34 patients receiving paclitaxel, rituximab, its biosimilar or obinutuzumab (first cycle, retreatment after 6 months or with persistent IRs). The primary objective was the incidence of IRs after premedication. Secondary endpoints included sedation due to antihistamines and time to readiness for discharge. Sedation was reported by patients on a scale of 0-4 (0 = none to 4 = extremely severe). No formal statistical analyses were planned given the exploratory nature of the study. Results: Adults primarily with cancer (n = 31 [91%]) were enrolled during the COVID-19 pandemic, from March 25 to November 23, 2020. The median age was 65 and 67 years in the IV cetirizine and diphenhydramine groups, respectively. The number of patients with IRs was 2/17 (11.8%) with IV cetirizine versus 3/17 (17.6%) with IV diphenhydramine. The mean sedation score in the IV cetirizine group compared to the IV diphenhydramine group was lower at all time points, including at discharge (0.1 vs 0.4, respectively). Mean time to discharge was 24 minutes less with IV cetirizine (4.3 hours [1.5]) versus IV diphenhydramine (4.7 hours [1.2]). This difference was greater (30 minutes less) in those ≥65 years of age (4.4 [1.3] vs 4.9 [1.0] hours). Regardless of whether patients received paclitaxel (n = 9) or an anti-CD20 (n = 25), patients had less chair time when premedicated with IV cetirizine. There were fewer treatment-related adverse events (AEs) with IV cetirizine (2 events) than with IV diphenhydramine (4 events). Conclusions: This was the first randomized, controlled trial evaluating IV antihistamine premedication for IRs and chair time. It was shown that IV cetirizine can prevent IRs, with less sedation, fewer related AEs and reduced chair time compared to IV diphenhydramine. This improves infusion center operations and patient experience. Clinical trial information: NCT04189588.