bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety assessment of trastuzumab diluted in 100 ml of saline in the treatment of HER2-positive breast cancer patients.
Authors: Abe Hajime , Mori Tsuyoshi , Kawai Yuki , Tomida Kaori , Kubota Yoshihiro , Umeda Tomoko , Tani Tohru 
Published: March 2020

e11555 Background: The infusion rate is considered to affect incidence and severity of infusion reaction (IR) caused by infusion of protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose followed by 30-minute infusion with 250 ml saline. We evaluated the safety of TRS intravenously administered over 30minutes with 100 ml saline to reduce burden of patients although safety of infusion with 250 ml saline is established. Methods: Women with HER2 positive breast cancer, ≥18 years and ≥55% left ventricular ejection fraction (LVEF) were registered in the study. Patients received 8mg/kg of TRS 250 ml over 90 minutes diluted in 250 ml saline followed by 6mg/kg of TRS in 100 ml saline over 30 minutes in a three-week cycle. The primary endpoint of this study was the incidence of infusion reactions, and secondary endpoints were as follows: incidence of adverse events and effects on cardiac function. Results: Between June 2011 and June 2012, a total of 31 patients were recruited; 24 for adjuvant therapy and seven with metastases. The median age was 59 years (range, 39 to 82). Hormone receptor was positive in 18 patients (58%). Previous treatment with anthracyclines was reported in seven patients and radiation therapy in fourteen patients. The total number of TRS doses ranged from 5 to 17 with the median of 15. Mild IR occurred in two patients and rash occurred in one patient at the first dose. However, no IR and adverse events were observed after reducing to 100 ml saline. The average LVEF measured every 3 months was between 62.3% and 64.8%. No significant decrease in LVEF was reported with the largest decrease of 8% in one patient at the 12th month on treatment. Conversely, brain natriuretic peptide levels tended to decrease as the number of received doses increased. None of the subgroup analysis (age groups, adjuvant vs. metastatic setting, previous anthracycline treatment, and previous radiotherapy) showed statistical significance. Conclusions: Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast cancer patients is considered safe based on results from the study. The safe treatment with shorter infusion time has benefit for both healthcare professionals and patients. Clinical trial information: UMIN000006710.
Role of hypertension on new onset congestive heart failure in patients receiving trastuzumab adjuvant chemotherapy for early breast cancer.
Authors: Maurea Nicola , Russo Giulia , Gori Stefania , Piscopo Giovanna , Cipresso Clemente , Coppola Carmela , Oliva Stefano , Cioffi Giovanni , Tuccia Fausto , De Laurentiis Michelino , Pacilio Carmen , Capasso Immacolata , Iaffaioli Rosario Vincenz , Tarantini Luigi 
Published: March 2020

e11556 Background: Adjuvant trastuzumab therapy improves survival of Human Epidermal growth factor Receptor 2 (HER2)-positive women with early breast cancer (EBC). Trastuzumab-induced cardiotoxicity is not uncommon, occurring prevalently asymptomatic in the first three months of therapy. In the setting of community patients, the incidence, timing and phenotype of new onset congestive heart failure (CHF) is unknown. Methods: 499 consecutive HER2-positive women (mean age 55+11) with EBC treated with Trastuzumab between January 2008 and June 2009 at 10 Italian institutions were followed-up for 1 year. We evaluated incidence, time of occurrence, clinical features associated with CHF. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography at baseline and 3-6-9-12 months during Trastuzumab therapy. Results: CHF occurred in 16 patients (3.2%), who were older and had a higher prevalence and higher degree of hypertension in comparison with patients who had not CHF. All CHF patients had a significant reduction in LVEF with a mean peak of – 12 points % detected at 3-month follow up. CHF occurred in 7 patients (44%) within 3-month follow-up, 4 patients (25%) between 3-6 months, 3 patients (19%) between 6-9 months and 2 patients (12%) between 9-12 months. Trastuzumab was discontinued in 10 of 16 patients and re-started in 5 after LVEF recovery. New onset CHF was predicted by the presence of hypertension (OR 2.9 [CI 1.1 – 7.9]. Conclusions: In clinical practice new onset CHF occurs seldom in HER-positive women with EBC, prevalently in the first six months of therapy. CHF is invariably associated with a significant reduction in LVEF and is predicted by a history of hypertension.
Lapatinib with trastuzumab for heavily treated HER2-positive metastatic breast cancer (mBC).
Authors: Sotelo Miguel J. , Manso Luis , Garcia Saenz José Ángel , Ciruelos Eva M. , Moreno Fernando , Mendiola Cesar , Callata Hector , Ghanem Ismael , Cabezas Santiago , Gonzalez-Larriba Jose-Luis , Diaz Rubio Eduardo 
Published: March 2020

e11561 Background: Trastuzumab and lapatinib show complementary and non-cross resistant mechanisms of anti-HER2 action. Dual HER2 blockade has been preclinically and clinically assessed with encouraging results. Trastuzumab and lapatinib combination is effective in terms of survival in patients with heavily pretreated HER2-positive mBC. We aim to report our experience with lapatinib plus trastuzumab in this setting. Methods: Descriptive retrospective study of trastuzumab plus lapatinib activity in patients with HER2-overexpressing metastatic breast cancer treated in two institutions from 01/2007 to 12/2012. The objective of this analysis is to report the response rate (RR), progression-free survival (PFS) and toxicity. Results: 23 HER2-positive mBC patients previously treated with trastuzumab received trastuzumab plus lapatinib based therapy. 15 patients (65%) received 2 or more previous lines. 17 patients (74%) had visceral disease. Chemotherapy (CT) was added to the dual HER2 blockade treatment in 13 patients (56%) whereas hormonotherapy (HT) was added in 8 patients (35%) and 2 patients (9%) received lapatinib plus trastuzumab without any other agent. Chemotherapeutic drugs most used were: capecitabine (54%) and vinorelbine (15%). RR: partial response 22% (5/23), stable disease 39% (9/23). Median of follow-up was 11 months. PFS in the overall population was 4 months. PFS in patients with CT was 5 months, while PFS in patients with HT was only 2. PFS in hormone receptor positive and negative was 3 and 5 months respectively. The most common toxicities were: diarrhea (48%), anemia (39%), asthenia (39%) and hand-and-foot syndrome (17%). Grade ≥ 3 toxicity was diarrhea (26%) and hand-and-foot syndrome (9%). The incidence of cardiotoxicity was 9% (grade 2). Conclusions: These findings suggest that dual HER2 blockade in combination with CT is feasible and active in heavily pretreated HER2-positive mBC patients. However, further investigation is warranted to demonstrate superiority over sequential blockade with trastuzumab and lapatinib in this setting.
Prediction of benefit from treatment beyond the first line in patients with metastatic breast cancer (MBC).
Authors: Bonotto Marta , Gerratana Lorenzo , Minisini Alessandro , Poletto Elena , Russo Stefania , Andreetta Claudia , Mansutti Mauro , Fasola Gianpiero , Puglisi Fabio 
Published: March 2020

e11565 Background: Despite the availability of several therapeutic options for MBC, palliative treatments beyond 1st line lack of predictive factors that could help clinical decision making. We aimed to determine which is the impact of benefit at 1stline into the benefit from subsequent therapeutic lines. Methods: We analyzed a consecutive series of 472 MBC patients treated with chemotherapy (CT) and/or endocrine therapy (ET) at the Department of Oncology of Udine, Italy, between 2004 and 2012. We evaluated Progression Free Survival at 1st (PFS1), 2nd (PFS2), 3rd (PFS3) and 4th (PFS4) line of treatment. Three distinct analyses were conducted: the first for the lines of CT, the second for the lines of ET and the third by considering both CT and ET as a line of treatment. A PFS longer than 6 months was defined as “6-month benefit". Results: Median Overall Survival was 34.5 mo (25th – 75th percentile: 14.5 – 58.8), median overall PFS1 and PFS2 was 8.9 mo and 4.3 mo respectively. Median PFS1 and PFS2 in CT lines only was 7 mo and 3.7 mo, respectively. Median PFS1 and PFS2 in ET lines only was 9.4 mo and 4.6 mo respectively. Overall, 289 patients (63.5%) presented 6-month benefit at 1st line, 128 (40.5%) at 2nd, 76 (33.8%) at 3rd and 34 (23.3%) at 4th. Not having a 6-month benefit in overall PFS1 was associated with a lack of benefit both at 2nd line (OR=0.48; p=0.0026) and at any line beyond the 1st (OR=0.39; p< 0.0001). Taking into consideration CT lines only, not having a 6-month benefit in CT PFS1 was associated with a lack of benefit both at 2nd line (OR=0.45; p=0.0072) and at any line beyond the 1st (OR=0.43; p=0.0026). A lack of benefit at the 1st ET line was not associated with further ET outcome neither in 2nd line nor in any line beyond the 1st. Stratification according to immunophenotype highlighted a statistical significance only among HER2 positive tumors (OR=0.2; p=0.0152 in 2nd line and OR=0.14; p=0.0036 beyond 1st line). Conclusions: Our results suggest that the absence of a “6-month benefit” in PFS1 predicts a lack of benefit in subsequent therapy lines, especially in HER2 positive disease. However, a lack of benefit at first line ET appears not to be detrimental to further anti-hormonal lines.
Relationship of anti-proliferative activity of TAS-108, a steroid anti-estrogen, and high expression of ERα in MCF7 cells.
Authors: Cheong Ye-Whang , Kim Young Choi , Kim Tae-Hoon 
Published: March 2020

e11566 Background: TAS-108 is an anti-estrogen that binds to both ERα and ERβ and has potent anti-proliferative activity in vitro and in vivo assay. Recently, the phase II clinical study of TAS-108 showed that it has competitive clinical benefic with lower level of adverse effects. However, the effect of TAS-108 on molecular mechanism, including ER dimerization, remains largely uninvestigated. Methods: The plasmids containing ERα or ERβ fused with N- and C-terminal fragments of firefly luciferase were constructed for split luciferase complementation assays. The resulting plasmids were transfected in HEK293 cells for 24 hr and TAS-108 was added to the media for 6 hr. For RT-qPCR of AREG and TFF1 and proliferation assay, ERβ was transfected in MCF7 cells for 24hr. The proliferation level was determined by measuring the fluorescent level induced by Prestoblue reagent. Results: Using split luciferase complementation assay, we determined that TAS-108 induced ERα/β heterodimerization about 100-fold more potently than ERα/α homodimerization. Increasing the ERβ level by transfection in MCF7 cells (MCF7-ERβ), potency of TAS-108 was increased significantly; 30nM TAS-108 was suitable to block the E2 mediated increase of AREG and TFF1 expression and significantly decrease proliferation of MCF7-ERβ. Conclusions: Taken together, these data suggest that TAS-108 has a higher affinity for ERα/β heterodimerization than ERα/α homodimerization and TAS-108 shows more effective anti-proliferative activity by blocking the expression of E2-induced proliferative genes when coupled with increased levels of ERβ. These findings also underscore the molecular role of ERβ in the biology and suggest the possibility of the compound inducing ERα/β heterodimerization as anti-breast cancer drugs.
Coagulation assays in breast cancer: Correlation of plasma D-dimer with tumor load and invasiveness in breast cancer patients.
Authors: Karabulut Senem , Kilic Leyla , Ciftci Rumeysa , Yildiz Ibrahim , Sen Fatma , Keskin Serkan , Tastekin Didem , Tas Faruk 
Published: March 2020

e11592 Background: Activated coagulation and fibrinolytic system in cancer patients is associated with tumor stroma formation and metastasis in different cancer types. The aim of this study is to explore the correlation of blood coagulation tests for various clinicopathologic factors in breast cancer patients. Methods: The study involves treatment-naive female breast cancer patients. Pretreatment blood coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), INR, D-dimer, fibrinogen levels and platelet counts were evaluated. Results: Between February 2010 and June 2011, 123 consecutive female patients with breast cancer were enrolled into the study. Median age of diagnosis was 51 years old (range: 26-82). 22 % of the group consisted of metastatic breast cancer patients. The plasma level of all coagulation factors revealed statistically significant difference between patient and control group except for PT (p<0.001 for all variables except for PT; p=0.08). Elderly age (>50 years) was associated with higher D-dimer levels (median 174 vs 345 U/ml, p=0.003). Metastatic patients exhibited significantly higher D-dimer values when compared with early breast cancer patients (median 205 U/ml vs 407.2 U/ml, p=0.049). Advanced tumor stage (T3&T4 vs T1&T2) was associated with higher INR (median 1.15 vs 1.09, p=0.05) and lower prothrombin activity (median: 82 % vs 70 %, p=0.025). Conclusions: Plasma D-dimer levels are elevated among metastatic breast cancer patients. Involvement of axillary lymph nodes and hormone receptor status does not seem to have an effect on coagulation parameters. For daily practice, D-dimer may be a suitable test for evaluation of disease extent before designing treatment strategy.
Tubular carcinomas of the breast: A comparison of features and survival outcomes versus low grade ductal and lobular carcinomas in the SEER database.
Authors: Romano Andrew Michael , Smolkin Mark E , Dillon Patrick Michael 
Published: March 2020

e11596 Background: Tubular carcinoma of the breast (TC) is a rare histologic subtype of breast cancer considered to have a favorable prognosis relative to other histologies. TC is by definition low grade. TC is described to have clinical behavior similar to low grade ductal and lobular breast cancers, but due to its infrequent presentation, long-term follow-up studies of TC are lacking. Methods: The Surveillance, Epidemiology and End Results database was queried to include the years 1988-2009, selecting for patients with either grade 1 TC or grade 1 ductal and lobular breast cancer (G1BC). Data collected included age at diagnosis, race, stage, receptor status, overall survival, and surgery type. Two Cox proportional hazard models were assessed for differences between TC and G1BC, adjusting for age at diagnosis. Results: In SEER 18, 115,945 cases of TC+G1BC breast cancer are found, with 6.1% classified as TC. Of TC cases, 91% are stage 1, while 71% of GIBC are stage 1. Presenting stage 3 or 4 disease occurred in only 4.7% of G1BC versus 0.68% of TC cases. Due to the rarity of advanced disease, we analyzed early stage disease. For early Stage (1-2) breast cancer, mean age was 61.5 years for TC and 63.5 years for G1BC. The TC cases were 92% white, 4% black, 97% Estrogen Receptor (ER) positive, 82% Progesterone Receptor (PR) positive. Of G1BC cases, 88% were white, 5% black, 96% ER positive, 84% PR positive. Treatment differed with 76% of TC patients receiving lumpectomy versus G1BC where 65% received lumpectomy (p<0.001). There was no significant difference in overall survival between Stage I TC and G1BC (p=0.98), or between Stage II TC and G1BC (p=0.075), with the survival estimate higher for TC. Conclusions: In this large-scale analysis, TC was limited to early stage disease and there was no difference in overall survival between patients with early stage TC and early stage GIBC. There were similar receptor statuses and baseline characteristics, but more conservative surgical treatment in TC. Because no survival difference exists for early stage disease, the finding of tubular histology to guide treatment decisions may not be warranted.
Bevacizumab for advanced breast cancer: Hope, hype, and hundreds of headlines.
Authors: Fralick Michael , Fung Christina , Ray Monali , Booth Christopher M. , Mallick Ranjeeta , Burke Matthew , Clemons Mark 
Published: March 2020

e11597 Background: On February 22, 2008, the Food and Drug Administration (FDA) granted accelerated approval for the use of bevacizumab (Avastin) in metastatic breast cancer. Based on the results of subsequent clinical trials this accelerated approval was revoked on November 18, 2011.In this study we categorize and analyze the newspaper reports related to bevacizumab use in advanced breast cancer. Methods: Using the FACTIVA media database, we reviewed all newspaper reports published in the United States and Canada from January 4,2002 to January 4, 2012 with the words “breast cancer” and “Avastin” or “bevacizumab”. Articles were classified as pre-approval (Jan 4 2002 – Feb 21 2012); approval (Feb 22 2008 – Nov 17 2011); or post-approval loss (Nov 18 2011 – Jan 4 2012). Information related to benefits, side effects, costs, interviewees, and article tone and theme were abstracted from each article by two independent reviewers. Differences between the 3 study phases were compared using the Chi square test. Results: 353 articles met our study inclusion criteria. The major article themes evolved over each study period. Reports having a positive headline tone (36%, 18%, 9%; p=0.0004) and/or positive article tone (42%, 19%, 9%; p<0.0001) declined with each study period. The proportion of articles discussing side effects (25%, 49%, 60%; p<0.0001) and financial costs (19%, 46%, 41%; p<0.0001) increased while those discussing efficacy decreased (82%, 59%, 15%; p<0.0001) with each study period. Drug representatives were most likely to be quoted in newspaper articles prior to bevacizumab’s approval (33%, 23%, 11%; p=0.015). Conclusions: Media reports are a common source of medical information for patients, practitioners, and policy-makers. Although we cannot discern cause from effect, we did observe substantial fluidity of media reports over time.
Comparative efficacy of everolimus versus fulvestrant for hormone-receptor–positive (HR+) advanced breast cancer (ABC) following progression/recurrence after first-line treatment: A network meta-analysis.
Authors: Bachelot Thomas Denis , Jerusalem Guy Heinrich Maria , Cikalo Maria , McCool Rachael , King Sarah , Duffy Steven , Glanville Julie , Varley Danielle , Zhang Jie 
Published: March 2020

e11602 Background: Everolimus (EVE), an oral mammalian target of rapamycin (mTOR) inhibitor, is approved in combination with exemestane (EXE) to treat postmenopausal women (PMW) with HR+, human epidermal growth factor receptor-2–negative (HER2–) ABC that progressed after nonsteroidal aromatase inhibitor therapy. Fulvestrant (FUL), an estrogen receptor antagonist, is another treatment option for PMW previously treated with endocrine therapy. However, the comparative efficacy of EVE + EXE vs FUL is unknown. Methods: Six randomized, controlled trials in HR+, HER2–ABC patients were identified by systematic literature review (Cochrane library, National Horizon Scanning Centre, and NICE Web sites) that formed a network permitting indirect comparisons of EVE + EXE or EVE + tamoxifen (TAM) vs FUL: BOLERO-2, CONFIRM, EFECT, Paridaens (2008), SoFEA, and TAMRAD. All 6 trials had EXE, TAM, or FUL 250 mg as the common comparator to form the network. Relative efficacy of EVE and FUL was obtained using a Bayesian network meta-analysis based on these 6 trials. The primary endpoint was local assessment of progression-free survival (PFS) or time to progression (TTP). The hazard ratio (HR) of EVE + EXE relative to FUL and its 95% credible intervals (CrI) were calculated. Evidence of a difference between treatments is suggested by the 95% CrI not including 1. A HR <1 indicates that the hazard rate is higher in the comparator group and that the treatment is more effective. Results: EVE + EXE was found to be more efficacious for PFS/TTP than FUL 250 mg (HR = 0.47; 95% Crl, 0.38-0.58) and more efficacious than FUL 500 mg (HR = 0.59; 95% Crl, 0.45-0.77). EVE + TAM was found to be numerically better for PFS/TTP than FUL 250 mg (HR = 0.65; 95% Crl, 0.40-1.04) and numerically better than FUL 500 mg (HR = 0.81; 95% Crl, 0.49-1.33). Conclusions: The indirect evidence from this analysis suggests that EVE in combination with EXE is more efficacious than FUL 250 and 500 mg in PMW with HR+, HER2– ABC that progresses after endocrine therapy. These data should be interpreted with caution as there is no randomized trial that directly compares EVE + EXE vs FUL.
Safety and efficacy of dicarbamin in patients with early breast cancer receving DAC (docetaxel, doxorubicin, cyclophosphamide) chemotherapy in adjuvant setting.
Authors: Kopp Mikhail V. , Koroleva Irina , Mochalova Anastasia , Shaplygin Leonid 
Published: March 2020

e12012 Background: One of the most serious potential side effects of chemotherapy is neutropenia. Grade 3 and 4 neutropenia is especially problematic because of increased incidence of infections, hospitalization, antibiotic treatment, necessity to reduce therapy intensity. The intensity of adjuvant chemotherapy is the key to successful treatment. Dicarbamin is agent for the prevention of chemotherapy-induced neutropenia. Dicarbamin therapy decreases dystrophic changes in myeloid progenitor cells and decreases the relative number of cells with signs of apoptosis. We conducted an analysis of efficacy of dicarbamin in patients during docetaxel-based chemotherapy. Methods: Between May 2011 and July 2012, 87 patients with early breast cancer were treated with adjuvant DAC regimens (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 every 3 weeks). All patients were female. All patients were treated with these regimens without prophylactic growth factor support. 42 patients of control (group A) were not given any prophylaxis of neutropenia. 45 patients (group B) were given dicarbamin 100 mg/day on day 5 before chemotherapy administration. Treatment with dicarbamin continued for all treatment period. Neutropenia was evaluated with Common Toxicity Criteria, Version 3.0. Results: Median age was 47 (29 – 55). Grade 4 neutropenia was reported in 13 (30.9%) patients treated without dicarbamin (A) and in 8 (17.7%) patients treated with dicarbamin (B). Grade 4 neutropenia was observed in 39 cycles in group A and in 22 cycles in group B (p=0.016). The beneficial effect of dicarbamin was also demonstrated by a quick recovery of granulocytes levels than in controls. In 17 (37.7%) patients treated with dicarbamin granulocytes levels were normal all period of chemotherapy. The dose intensity of chemotherapy was more in group with dicarbamin prophilaxis. The toxicity of dicarbamin was not observed. Conclusions: Dicarbamin is an active agent for prophylaxis of neutropenia without specific toxicity. The intensity of the DAC-chemotherapy was more in group with dicarbamin prophilaxis.