bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of taxanes followed by anthracyclines as neoadjuvant therapy in HER2-negative breast cancer (BC): Analysis of everyday clinical practice.
Authors: Alanya Rodríguez Enrique , Falo Zamora Catalina , Gil Gil Miguel J. , Anna Petit , Ortega Raul , Fernandez Adela , Morilla Idoia , Stradella Agostina , Cobo Sara , Pernas Simon Sonia 
Published: September 2018

e12112 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy for BC has been related with survival, and the sequence of anthracyclines followed by taxanes (AT) has been the strategy to achieve this response. Some studies suggest that the reverse sequence (TA) might improve cancer outcomes. The aim of our study was to compare clinical response, toxicity and efficacy in terms of pCR rate (ypT0/pTis, ypN0) between both sequences Methods: A retrospective cohort study was designed. TA cohort received Docetaxel (100 mg/m2) x 4, followed by AC (60/600 mg/m2) x 4. AT cohort received the reverse sequence at the same doses. To be included, it was necessary to have received at least one cycle in the planned sequence. Logistic regression analysis was performed to obtain a model adjusted by age, menopausal status, tumor size, nodal status, grade, estrogen receptor (ER), progesterone receptor, and Ki67 Results: From June 2008 to December 2015, 135 consecutive patients with stage II – III HER2 negative BC were treated: TA (n = 48) and AT (n = 87). No significant differences in patient characteristics between groups were found, except for histological grade 3 (63.2% to AT vs. 35.4% to TA), and ER negative (41.4% to AT vs. 22.9% to TA). The pCR rate for TA was 16.7% (8 of 40) vs. 14.9% (13 of 74) for AT. Multivariate logistic regression analysis found OR = 3.65 to achieve pCR for TA (95%CI 1.03 – 12.94; p = .045). We also performed the same analysis for two clinical parameters of response: Neoadjuvant response index (NRI) with cut-off > 0.5 (OR 3.96, 95%CI 1.42-11.08; p = .009) and Clinical response (CR) > 50% (OR 3.65, 95%CI 1.03 – 12.94; p = .045). These parameters were correlated in our series with DFS (p = .011 to NRI and p = .00023 to CR) and OS (p = .034 to NRI and p = .0014 to CR) using the Kaplan-Meier method. No significant differences between rates of either, hospitalizations, neutropenia or dose intensity were found Conclusions: Sequence of T followed by A was slightly significantly more effective to achieve pCR as well as better clinical outcomes in our series of HER2 negative BC than classical sequence of A followed by T, and support the design of large prospective studies to confirm these results
Prognostic factors in breast cancer patients evaluated by PET/CT prior to neoadjuvant chemotherapy.
Authors: Farrugia Mark K , Jacobson Geraldine M. , Salkeni Mohamad Adham 
Published: September 2018

e12113 Background: Neoadjuvant chemotherapy (NAC) is an important modality in breast cancer treatment. We sought to identify pre-treatment prognostic factors in patients who had positron emission tomography paired with diagnostic quality contrast-enhanced CT (PET/CT) prior to neoadjuvant chemotherapy with respect to pathologic complete response (pCR) , survival and relapse-free survival (RFS). Methods: We retrospectively analyzed 118 breast cancer patients who had pre-treatment PET/CT imaging and received NAC from 2008-2014. We collected data on molecular markers, PET/CT, pCR, survival, and disease status. Results: The median follow up was 44 months(range 7.3-101.5),median age was 51 years; 47% were stage II, 53% stage III. 52% of patients had hormone receptor (HR) positive/HER2 negative disease, 31% of tumors were HER2 positive, and 17% of tumors were triple-negative. 92.5% with HER2 positive tumors received NAC containing at least one HER2 targeted agent. Pre-treatment standard uptake value (SUV) max of the primary breast tumor showed no statistically significant relationship to survival, RFS, or pCR. PET avid (>2 SUV) extra-axillary nodes such as internal mammary and supraclavicular was associated with a non-statistically significant trend towards reduced RFS (p=0.06, HR=0.13-1.06). pCR overall was 37.5% for HER2 positive tumors, 15% in triple-negative tumors, and 8% in HR positive/HER2 negative tumors. Log-rank analysis with post-hoc pairwise comparisons showed a significant difference between the RFS of triple-negative tumors and HER2 positive tumors (p=0.001), while comparison between HR positive/HER2 negative and HER2 positive was not statistically significant (p=0.11). Multivariate cox regression analysis, which included grade and stage of tumors, showed HER2 positivity to be associated with a favorable outcome (p=0.04, HR=0.22 (0.05-0.94)). Conclusions: Within this cohort, pre-treatment SUV max of the primary tumor showed no prognostic value with regard pCR or RFS. PET avid extra-axillary metastasis trended towards reduced RFS. Patients with HER2 positive tumors had the highest pCR and RFS comparable to classically favorable subgroups such as HR positive/HER 2 negative.
Prognostic value of Ki-67 labeling index according to age in patients with non-metastasic triple-negative breast cancer.
Authors: Zenzola Victor , Cabezas-Quintario María Antonia , Correa Andrea , Moreno Irene , Pedregal Manuel , Rojo Federico , Arguelles Miguel , Perez Fernandez Elia , Garcia-Foncillas Jesus 
Published: September 2018

e12118 Background: The prognostic value of Ki67 in triple negative breast cancer (TNBC) is yet unclear because the cut-off points employed differ widely and its predictive effect may vary according to age. The purpose of this study was to analyze the role of Ki-67 among patients with TNBC, and determined the optimal Ki-67 cut-off point to demonstrate its prognostic relevance associated with patient age and treatment strategy. Methods: 201 patients treated for primary TNBC from 1999 to 2014 were identified from the breast surgery database. Clinicopathologic characteristics and outcomes were compared between patients treated with neoadjuvant or adjuvant chemotherapy. We used time-dependent receiver operating characteristic (ROC) curve and time-dependent area under the ROC curve (AUC) to evaluate the discriminative ability of Ki-67 at 3 and 5 years of follow up. A Ki-67 cut-off point was set up to maximize sensitivity and specificity. Interaction effect between age and Ki-67 on disease-free survival (DFS) and overall survival (OS) was evaluated by stratified analysis. Results: There was a non-significant Ki-67 cut off value to predict OS and DFS at 3 and 5 years neither in the whole serie (201) nor in the adjuvant group (125), and only a slightly better threshold for DFS in the neoadjuvant one (N = 46) at 5 years (AUC = 0.697). According to the coordinates of the ROC curves, the best cut-off point for Ki-67 was 60%. In the multivariate analysis (COX proportional hazards regression), high Ki-67 ( > 60%), was a poor prognostic factor for DFS in patients > 40 yo. Among the patients < 40 yo, high Ki-67 was a better prognosis factor. Conclusions: Our data suggest that a threshold of Ki-67 of 60% could provide a usefull tool to define patients with significantly different outcome in TNBC.
Association between ER±36 and PR A/B overexpression in trastuzumab resistant HER2+ breast cancer cell lines.
Authors: Contreras Sergio , Torres Eduardo Rey , López José Anselmo , García Eric Alejandro , Ventura José Luis , Badillo Ernesto , Lara - Torres Cesar , Aguilar Diana Elodia , Ibarra María de los Ángeles , Zentella Dehesa Alejandro , Aguayo Alvaro 
Published: September 2018

e12501 Background: Clinical importance of the ERa36 isoform is poorly understood. It is present in 40% of the cells that lack the ERa66 and has also been linked to proliferation and invasion. It is also related to expression of phospho-src. Coincidently, phospho-src over-expression is associated to trastuzumab-resistance. We analyzed the possible link between trastuzumab-resistance and over expression of estrogen and progesterone receptors in HER2+ cell lines with trastuzumabTM chronic treatment. Methods: BT-474 and SKBR-3 cells were treated with trastuzumabTM with 4 ug/ml for 8 weeks, then 10 ug/ml for 2 weeks and with 20 ug/ml for the last 2 weeks. Protein extracts for western blot analysis where obtained from paternal cell lines and at 4, 8 and 12 weeks during treatment. Western blots were done for total and phosphorylated HER2, total and phosphorylated Src, aER and PR A/B. Densitometry analysis was applied to the western blots with the image-jTM software. Surface HER2 status was determined by flow citometry. Results: Treatment led to increase in T-HER but no changes in p-HER, T-Src and p-Src where increased, 5.27% and 18.01% respectively compared to baseline. 36KDa and 46KD aER isoforms increased with treatment. The most significant increase was in PR A expression. Western Blot for total HER2 and flow citometry for surface HER2 status revealed a link between HER2 and hormone receptor over-expression in TrastuzumabTM resistant BT-474 cells while both where absent in trastuzumabTM resistant SKBR-3 cells. Conclusions: A variety of trastuzumabTM-resistance mechanisms have been established, some of which include over-expression of p-Src. So far, none of them had been associated with expression of hormone receptors. We observed two molecular phenotypes associated to trastuzumabTM resistance: over-expression of HER2 linked to over-expression of hormone receptors in BT-474 cell and down-regulation of HER2 with no change in the hormone receptor status in the SKBR-3 cells. Our results suggest that over-expression of ERa36, ERa46 and PR A/B could represent a novel mechanism of trastuzumabTM resistance.
Efficacy of pertuzumab in combination with trastuzumab and a taxane in first-line treatment for metastatic breast cancer (MBC): A multicenter, retrospective, observational study.
Authors: Gamucci Teresa , Mentuccia Lucia , Sperduti Isabella , Gelibter Alain , D'Onofrio Loretta , Cassano Alessandra , Iezzi Laura , Botticelli Andrea , Pizzuti Laura , Moscetti Luca , Barchiesi Giacomo , Scinto Fedele , Carbognin Luisa , Cursano Maria Concetta , Foglietta Jennifer , Rossi Ernesto , Barni Sandro , Graziano Vincenzo , Magnolfi Emanuela , Vici Patrizia 
Published: September 2018

e12504 Background: Pertuzumab (P) , Trastuzumab (T) and Docetaxel (D) is standard first-line treatment in patients (pts) with HER2 + metastatic breast cancer (MBC). This multicenter retrospetive observational study was performed to evaluate the activity of P and T in combination with D or Paclitaxel (Tx) in real world HER2 + MBC pts. Methods: We identified HER2 + MBC pts treated with P, T and D or Ptx optionally followed by P, T and endocrine therapy (ET) maintenance in hormone positive (HR+) BC, in 17 Italian cancer centres between 09/2012 and 08/2016. Overall Survival (OS) and Progression Free Survival (PFS) were calculated by the Kaplan-Meier product-limit method. Log-rank test was used to assess differences between subgroups. Results: 191 pts were included in our analysis. Pts characteristics: median age 54 years (range 29-80); PS 0 in 127 (67%) pts and PS 1 in 54 (28%); 107 (56%) had visceral metastases (mts), 23 (12%) only bone mts and 28 (15%) brain mts, 130 (68%) were ER/PgR +. 76 pts (40%) were metastatic at diagnosis; 148 (78) were treated with D while 43 (22%) with Tx. The ORR was 78% (CI 95% 72-84), RC 18% and RP 60%, only 10 (5%) had PD. To date, of the 54 pts treated with ET maintenance, 26% had a further improvement of response (7 pts had RC). At median follow-up of 17 months (mo) (range 6- 52), median PFS was 20 mo (95% CI 14-26) and median OS at 2 years was 80%. No differences in PFS were found for age (p = 0.92), PS (p = 0.18), receptor status (p = 0.57), visceral mts (p = 0.54) and chemotherapy (cht) type (p = 0.47), whereas number of mts site (1 vs > 1) affected PFS (28 vs 16 mo, p = 0.002). Moreover median PFS in naïve pts and in pts pretreated with only cht was 28 mo (95% CI, 20-36) and 27 mo (95% CI, 16-38) respectively, whereas in pts pretreated with T it was 12 mo (95% CI 16-38 p 0.002). In HR+ pts ET maintenance together with P and T had an impact on PFS (28 vs 15 mo, p = 0.01). Conclusions: Our analysis confirms, in real world HER2 MBC pts, the efficacy of P, T and a taxane combination in first line treatment; in this population PFS was shorter in pts pretreated with T. ET maintenance in association with P and T in HR+ pts improved PFS. Data collection is ongoing and update results will be presented.
Inter-laboratory evaluation of a novel DEPArray-HER2 FISH assay.
Authors: Gerber Amanda , Koenig Lisa , Millner Lori , Strotman Lindsay , Sero Valeria , Manaresi Nicolò , Kasimir-Bauer Sabine , Bischoff Farideh Z. 
Published: September 2018

e12506 Background: Fluorescent in Situ Hybridization (FISH) is a method currently used for detection and assessment of HER2 gene amplification. Although clinical guidelines set forth by CAP/ASCO exist to ensure accuracy, limitations in HER2test results due to sample preparation, assay-conditions and tumor heterogeneity remain unresolved. We have successfully demonstrated analytical confidence in performing HER2 FISH on DEPArray™ sorted and recovered tumor cells. In this study, we aimed to evaluate inter-laboratory concordance of the DEPArray™ HER2-FISH assay. Methods: Three laboratories equipped with the DEPArray™ were designated as testing sites for this study. Positive control SKBr3 cells embedded in paraffin as well as 20 invasive breast carcinoma FFPE samples were blinded and evaluated by each of the three labs. Control and patient samples were processed through the DEPArray™ beginning with dissociation of the FFPE curls followed by single-cell image-based cell sorting to separate and recover pure distinct tumor cell populations prior to HER2 FISH analysis. Data was only obtained when ∼200 intact cytokeratin+/vimentin-/DAPI+ tumor cells from each sample were recovered and used for subsequent FISH using a standard dual-color HER2/CEP17 FISH procedure. Results: Overall, 80% concordance between DEPArray™-HER2 and conventional HER2 (6 HER2 negative and 10 HER2 positive) was observed between lab(s) and the conventional HER2 method. In each of 4 cases, a discordant HER2 result was reported by one of three sites. In three of these discordant cases, the DEPArray™ HER2 ratio was reported as amplified while the conventional result was negative. In the remaining discordant case, the converse was observed by one site; however, this case was initially evaluated 15 years ago. All three sites correctly scored the SKBr3 positive control cells. Conclusions: The results showed a high concordance rate of correct HER2 status classification. This data further supports the understanding that tissue heterogeneity can indeed give rise to discordant results that may consequently affect treatment options for patients. We demonstrate that sample preparation by DEPArray™ may aid in a more precise classification for tumor biomarker status.
A real-world retrospective study of apatinib plus chemotherapy in metastatic breast cancer.
Authors: Zhu Anjie , Yuan Peng , Wang Jiayu , Ma Fei , Luo Yang , Fan Ying , LI Qing , Zhang Pin , Xu Binghe 
Published: September 2018

e12507 Background: Antiangiogenic therapy in combination with chemotherapy has shown improved clinical outcome in advanced breast cancer(ABC). Apatinib is an orally administered tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2), which exhibited objective efficacy in metastatic breast cancer(MBC). We performed a retrospective observational analysis to evaluate the efficacy and safety of apatinib plus chemotherapy in the real-world practice of patients with MBC. Methods: Patients who have failed at least one prior chemotherapy regimen for metastatic disease were included in this study. The primary endpoint was progression free survival(PFS). Secondary end points included objective response rate(ORR), clinical benefit rate(CBR), overall survival(OS) and safety. Data analysis included association between clinicopathological characteristics or treatment choice and PFS. Results: Of the 23 patients analyzed, 14(60.9%) received plant-derived anticancer agents combined therapy and 9(39.1%) combined with non-plant-derived agents. Objective response rate(ORR) was 34.7% and clinical benefit rate(CBR) reached 52.2% on last tumor assessment. With a median follow-up of 9.0 months, the estimated median PFS and OS were 5.4 months (95%CI 3.5-7.3) and 8.2 months (95%CI 4.7-11.7), respectively. Toxicities were tolerable or could be clinically managed.The most frequently observed adverse events (AEs) of all grade were hypertension, myelosuppression, hand-foot syndrome, proteinuria, fatigue and gastrointestinal reaction. The most common grade 3/4 treatment-related AEs were myelosuppression(39.1%) and gastrointestinal reaction(17.4%). Conclusions: In this retrospective observational study, combination of apatinib with chemotherapy demonstrated clinically relevant efficacy and tolerability in metastatic breast cancer.
Circulating tumor cells and genomic profiling of patients with ERBB2 mutant, HER2 non-amplified metastatic breast cancer treated with neratinib.
Authors: D'souza Anishka , Shishedo Stephanie , Spicer Darcy V. , Welter Lisa , Jiang Yuanfei , Hyman David Michael , Solit David B. , Ma Cynthia X. , Bose Ron , Cutler Richard E. , Eli Lisa , Hicks James B , Kuhn Peter , Lu Janice M. 
Published: September 2018

e12554 Background: ERBB2 mutations in the absence of gene amplification are rare, with an incidence of 2-4%. Neratinib is a HER2/EGFR tyrosine kinase inhibitor being evaluated for use in ERBB2 mutated breast cancer. Neratinib has been found to have clinical activity on heavily pre-treated ERBB2 mutant breast cancer patients. We are evaluating the response and genomic profiles of 3 postmenopausal patients with metastatic ERBB2 mutant/non-amplified breast cancer receiving neratinib and fulvestrant NCT01953926, NCT01670877. Methods: Samples were collected at different points during treatment and CTCs were identified. Other representative cells were tracked but not classified as CTCs. CD45-CK+ cells with cytoplasmic and/or nuclear apoptosis were defined as CTC-Apoptotic. CD45- cells expressing little to no CK but otherwise meeting morphological criteria for CTCs are CTC-LowCK. CD45-CK+ cells with small nuclear size are CTC-SmallCK. Single CTCs will be analyzed using whole genome copy number variation to determine chromosomal alterations. Results: The patients had an average of 4.7 lines of therapy for metastatic disease before neratinib. Two had stable disease and one had progression. The patient who progressed had a rise in the number of CTCs from 37 to 52 cells/ml and drop in apoptotic cells from 5 to 0 cells/ml. Conclusions: The high CTC count of the patient who progressed may suggest more aggressive disease. The drop in the apoptotic cell count may correlate with a failure to respond to therapy. Samples have been sent for copy number variation profiling. The goal is to identify any genomic amplifications or deletions associated with clinical response and progression after targeted therapy. We hope to demonstrate the timeframe of tumor evolution in response to therapy and provide a framework for the use of fluid biopsies to monitor disease progression. [Table: see text]
Nab-paclitaxel in clinical practice: Preliminary data from the mantel study.
Authors: Garrone Ornella , Saggia Chiara , Bergnolo Paola , Beano Alessandra , Castiglione Federico , Vanella Paola , Turletti Anna , De Conciliis Enrico , Vellani Giorgio , Denaro Nerina , Bellini Elisa , Miraglio Emanuela , Merlano Marco Carlo 
Published: September 2018

e12561 Background: Metastatic breast cancer (MBC) is an incurable disease. The main goals of treatment are palliation, symptoms control, preserving QoL and prolonging survival. New drugs have contributed to ameliorate the outcome of MBC patients (pts) by increasing response rates (RR) progression free survival (PFS) and, in some setting, overall survival (OS). Taxanes are the most effective drugs in the management of MBC. Nab-Paclitaxel (Nab-P), a solvent-free albumin-bound taxane with high tumor retention, showed antitumor efficacy, and limited toxicity in MBC pts. Aim of the present study is to evaluate the activity and safety of Nab-P in clinical practice. Methods: MANTEL is a retrospective, multicenter, observational study, designed to collect biological and clinical data of MBC treated with Nab-P, from its availability in Italy. Objectives of the study are PFS, correlation between response and tumor biological characteristics and safety. Results: Up to date 137 cases were collected from 9 centers. Main patients’ characteristics were: median age 58 y (32-82) including 40 pts over 65, median ECOG PS 0 (0-2), ER/PgR positive 118 pts (86.1%), Triple Negative 11 pts (8%), most common metastatic sites: bone 100 pts (73%), liver 77 pts (56.2%), soft-tissues 72 pts (52.5%), lung 38 pts (27.7%), CNS 7 (5.1%) median number of organs involved: 2 (1-5), median number of previous chemotherapy regimens for advanced disease: 2 (0-9). Preliminary results were: 4 CR (3%), 34 PR (24.8), 35 SD (25.5%), 54 PD (39.4%) and 10 NE (7.3%), CB was observed in 52 pts (37.9%). Median number of cycles administered was 5 (1-15). Six pts are still on treatment. Median PFS is 4.2+ months (0.3+ - 34). G3-4 leucopenia and neutropenia were observed in 6 (4.3%) and 11 pts (8%) respectively, anemia (all grades) in 51 pts (37.2%). 65 pts (47.4%) experienced neuropathy (G3 in 6 pts), 87 (63.5%) fatigue (G3 in 4) and 20 pts (14.6%) G1-2 arthro-myalgia. 99 pts (72.2%) received standard every 3-weeks schedule. 34 pts (24.8%) required dose reduction due to toxicity. Conclusions: Nab-P is feasible in unselected MBC pts. No concerns about toxicity in this real life population including large number of elderly and heavily pretreated pts. The study is ongoing.
Treatment patterns and associated adverse events among patients with metastatic triple-negative breast cancer.
Authors: Kaklamani Virginia G. , Schultz Neil M. , Irwin Debra E. , Fulcher Nicole , Noxon Virginia , Wu Jun , Pandya Bhavik J. , Kim Ruth , Barlev Arie , Flanders Scott 
Published: September 2018

e12576 Background: Triple-negative breast cancer (TNBC) accounts for 10–20% of all breast cancers and about 4% are metastatic (mTNBC) at diagnosis. This research aims to describe treatment patterns and associated adverse events (AEs) among mTNBC patients. Methods: MarketScan Commercial Claims and Encounters and Medicare Supplemental Database, linked to an oncology EMR database, was used to identify patients with mTNBC. Demographic factors, clinical characteristics, mTNBC treatment patterns (treatment type and initial regimen), and the incidence of associated AEs (rates per 100 person-years) were tabulated. Patients seen in oncology practices between January 1, 2011 and June 30, 2015 were included in the study and were required to have continuous enrollment overlap in the administrative claims data for 6 months before the first diagnosis and throughout the variable-length follow-up period. Follow-up ended due to death, end of continuous enrollment, or end of study (whichever occurred earlier). Results: The study identified 163 mTNBC patients with a mean age of 55 years. The average length of follow-up was 569 days and 34% died during the study period. Diabetes mellitus (22%) and anemia (16%) were the most common comorbid conditions at baseline. During the follow-up period, the majority of mTNBC patients received treatment (76%); the most common first-line treatments included cyclophosphamide (60%), paclitaxel (56%), doxorubicin (52%), carboplatin (25%), and docetaxel (23%), averaging 96 days in duration. In 47% of patients, treatment ended due to a switch. Over 96% of the patients experienced at least one AE during treatment, the most common being hematological (neutropenia, leukopenia, and anemia), gastrointestinal (nausea and vomiting), and other (pyrexia, fatigue, and dyspnea) [see table]. Conclusions: Several different chemotherapy agents were used to treat mTNBC. Adverse events were common among mTNBC patients initially treated with chemotherapy; the highest incident AEs were hematological. [Table: see text]