bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor cells (CTCs) in peripheral blood of primary breast cancer patients
Authors: Rack B. K. , Schindlbeck C. , Hofmann S. , Schneeweiss A. , Rezai M. , Beckmann M. , Pantel K. , Schneider A. , Sommer H. , Janni W. 
Published: March 2020

10595 Background: Detection of CTCs has been shown to predict decreased PFS and OAS in metastatic breast cancer, whereas only limited data has been published in the adjuvant setting. We evaluate the role of CTCs in peripheral blood at primary diagnosis and during adjuvant chemotherapy, endocrine and bisphophonate treatment within the SUCCESS-Trial (n=3,658 pts). Methods: We analyzed 23ml of peripheral blood from 1767 N+ and high risk N- primary breast cancer pts before systemic treatment. 852 of these pts have undergone follow-up blood sampling after completion of chemotherapy. The presence of CTCs was assessed with the CellSearchSystem (Veridex, Warren, USA). Briefly, after immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies to distinguish epithelial cells and leukocytes. Results: 10% of pts with a blood sampling before systemic treatment (n=170) showed >1CTC before the start of systemic treatment (mean 13, range 2–827). While we found 2 CTCs in 5% of pts, 3% had 3–5 CTCs and 1% 6–10 and >10 CTCs each. The presence of CTCs did not correlate with tumor size (p=.07), grading (p=.30), hormonal status (p=.54) or Her2-Status of the primary tumor (p=.26). However, we observed a significant correlation with the presence of lymph node metastases (p=.015). None of 24 healthy individuals showed more than 1 CTC. Among those 852 pts with follow-up blood sampling after the completion of cytostatic treatment, 11% were CTC positive before starting systemic treatment (mean 7, range 2–166), while 7% of patients presented with >1CTC after completion of chemotherapy (mean 6, range 2–84). Of those, initially CTC positive, 10% remained positive (n=9) and 90% had a negative CTC test after chemotherapy (n=82). Of those initially CTC negative, 93% remained negative (n=711), whereas 7% returned with a positive CTC test (n=50) (p=.24). Conclusions: Our data show good feasibility of this highly standardized and easily applicable approach for the detection of CTCs in a large number of primary breast cancer patients. In a considerable number of patients, persistent CTCs can be detected after completion of cytostatic treatment. Whether this finding is prognostically relevant will have to been shown with longer follow-up of the SUCCESS-trial. No significant financial relationships to disclose.
Preoperative sodium concentration as a possible predictor of survival in patients with renal cell carcinoma
Authors: Vasudev N. S. , Brown J. E. , Brown S. R. , Cocks K. , O'Donnell D. , Patel P. M. , Harnden P. , Banks R. E. , Selby P. J. 
Published: March 2020

10601 Background: Conventional renal cell carcinoma (RCC) has a variable natural history, and determining individual prognosis is important to guide management. In this cross-sectional study of RCC, a large number of parameters including hematological and biochemical as well as traditional tumor-related factors have been assessed for their prognostic significance. Methods: Consecutive, unselected patients undergoing nephrectomy for newly diagnosed RCC were invited to participate. Primary end-points were overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). A subset analysis of patients presenting with localized N0 disease was planned. Univariate and multivariate Cox's proportional hazards models were used. Results: 212 patients with RCC formed the study population. Tumor-related factors including grade, stage, presence of necrosis and vascular invasion were prognostic for survival on multivariate testing, in agreement with previous reports. In multivariate analyses pre-operative serum sodium (sNa) was found to be independently and significantly associated with OS and DFS when considered as a continuous variable (see table ). In a further exploratory analysis for all patients when sNa was dichotomized into above/below the median value (139 mmol/l; normal range: 135–145 mmol/l), 3-year OS estimates above and below the median were 74%, 95% CI [64%, 85%] and 54%, 95% CI [44%, 64%]; corresponding figures for 5 years were 68%, 95% CI [54%, 81%] and 44%, 95% CI [33%, 56%]. Conclusions: We have confirmed the prognostic value of traditional tumor-related factors but, to our knowledge, these are the first data to demonstrate that pre-operative sodium concentration may be an important factor associated with survival in patients with RCC. This result suggests that sNa should be considered with established prognostic parameters in modeling survival in RCC. [Table: see text] No significant financial relationships to disclose.
Assessment of tumour size and its relationship to nodal involvement in multifocal and multicentric breast cancer
Authors: Rezo A. , Rodins K. , Davis A. J. , Shadbolt B. , Zhang Y. , Huynh F. , Dahlstrom J. ,   ACT & SE NSW Breast Cancer Treatment Group (ACT& SE NSW BCTG)
Published: March 2020

10602 Background: The AJCC/UICC staging system categorises tumour size in multifocal and multicentric breast cancer (MMBC) using the largest dimension of the largest focus of tumour. This under-estimates the total tumour burden and therefore may under-estimate the potential of these tumours to metastasise. This study tests the hypothesis that an aggregate measurement of tumour size in MMBC is more closely related to nodal status than the size of the largest focus. Methods: This prospective cohort study involved women with ipsilateral invasive breast cancer with known nodal status using data from the ACT & SENSW BCTG database from July 1997 to June 2004. Pathology reports were reviewed to obtain tumour size in the unifocal group and nodal status in all women. The histopathology of MMBC cases were reviewed measuring all tumour foci that were recorded as: (1) the diameter of the largest deposit (LD), (2) the aggregate diameter (AD) of all deposits, and (3) a calculation of the aggregate volume (AV) using the largest dimension of each focus. The MMBC dimensions were compared with unifocal cancers and against nodal status using a multivariate logistic regression analysis and compared against each other using a stepwise method to determine which method is most predictive of nodal involvement. Results: 795 women met the criteria for study entry: 139 (17.5%) had MMBC and 656 (82.5%) had unifocal disease. When adjusting for tumour size method of measurement in MMBC, there was strong agreement between the AD MMBC and unifocal groups in terms of nodal status (p=0.7). Conversely, there were statistically significant differences in nodal status using LD (p=0.008) and AV (p=0.02) measurements in MMBC when compared to the unifocal group. Within the MMBC group the aggregated diameter measure was most significantly related to nodal status (p=0.001). Conclusions: The results of this study confirm that the current tumour staging system in MMBC under-estimates the potential for nodal spread and that aggregate diameter is more clinically useful. Nodal status is used in this study as a surrogate for tumour behaviour. Further studies are underway to assess relationship of aggregate size of MMBC to relapse and survival. No significant financial relationships to disclose.
Investigating tamoxifen resistance in the luminal B estrogen receptor positive breast cancer subtype: Tailoring treatment in hormone responsive breast cancer
Authors: Loi S. , Sotiriou C. , Haibe-Kains B. , Lallemand F. , Conus N. , Piccart M. J. , Speed T. , McArthur G. A. 
Published: March 2020

10603 Background: We recently reported that the two estrogen receptor (ER) positive breast cancer (BC) molecular subtypes can be defined by their expression of proliferation genes using a gene expression index (GGI): the luminal A and B subtypes have low and high levels respectively (J Clin Onc, in press). When treated with adjuvant tamoxifen, luminal A tumors have a good prognosis, however the clinical outcome of the luminal B subtype was poor. This study aimed to explain the biological basis for these observations using global gene expression profiling and an in vitro model of ER+ BC. Methods: 246 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy were analyzed with affymetrix gene expression arrays and evaluated using gene set enrichment analysis (GSEA). ER+ MCF-7 BC cells (control) treated with tamoxifen (TAM) and heregulin (HRG) were used to investigate molecular pathways identified using GSEA. Results: We found that a gene set suggesting ERBB2 pathway activation was significantly enriched in the luminal B subtype (p=0.02). Only 10% of samples overexpressed HER2 by immunohistochemistry, suggesting that activation of HER2 signaling pathways is independent of HER2 overexpression and may contribute to TAM resistance in this subtype. To validate this hypothesis, MCF-7 cell-lines were treated with HRG (HRG-MCF7) to create a model of ERBB2 pathway activation. HRG-MCF7 cells displayed phosphorylation of HER2/3 without HER2 overexpression. Treatment with HRG overcame TAM induced cell cycle arrest with higher S-phase fraction (p<0.01) and increased anchorage- independent colony formation (p<0.01). Gene expression profiling confirmed significant enrichment of the ERBB2 gene set (p<0.01) and higher GGI levels (p=0.02) in HRG-MCF7 cells compared with control. Conclusions: HRG-MCF7 cells may be useful as an in vitro model of the TAM resistant luminal B subtype. In this group, targeting activated HER2 signaling may be a helpful treatment strategy despite the lack of HER2 overexpression. Our data suggests that agents like lapatinib may be effective only in the luminal B and not the luminal A tumors, demonstrating the importance of stratifying by subtype in future clinical trials of ER+ disease. No significant financial relationships to disclose.
Evaluation of gemcitabine plus carboplatin in pretreated, metastatic breast cancer patients: Final analysis of a phase II trial
Authors: Laessig D. , Vehling-Kaiser U. , Stemmler H. J. , Fasching P. , Melchert F. , Koelbl H. , Stauch M. , Scharl A. , Morack G. , Heinemann V. 
Published: March 2020

1074 Background: There is an increasing proportion of metastatic breast cancer patients (pts) who have been exposed to anthracyclines and taxanes either during perioperative treatment or during intial therapy of metastatic disease. The efficacy of gemcitabine plus cisplatin has been consistently demonstrated in several trials. This study evaluates the combination of gemcitabine plus carboplatin as a treatment option for intensively pretreated breast cancer pts. Methods: Metastatic breast cancer pts were treated with gemcitabine (1,000 mg/m2 iv on days 1 and 8) and carboplatin (AUC 4 iv on day 1) in a 3-week regimen. The trial was performed as a 2-stage phase II study according to the optimal design described by Simon (p0 = 0.1, p1 = 0.3, a = 0.05, β = 0.1) with overall remission rate (according to RECIST) as the primary objective. Results: 39 pts were recruited, median age was 60 years (29–77 yrs): median Karnofsky performance status was 90% (range, 70–100%), 77% of pts were ER- and/or PR-positive, and 28% of pts presented with Her-2 overexpression (IHC 3+ or FISH-positive). 87% of pts had visceral metastasis and 79.5% had =2 sites of metastasis. All patients had received prior chemotherapy and 92% of pts had received prior anthracyclines (87%) and/or taxanes (67%). Prior endocrine therapy had been applied to 77% of patients. Median follow-up time was 13.2 months (1–27 months) during which 207 treatment cycles were documented with a median number of 5 cycles per pt (range 1–12). A CR was observed in 1 pt, a PR in 11 pts for an overall remission rate of 31% (95%-CI: 17–48%). Stable disease was documented in 12 pts (31%) resulting in a disease control rate of 61.5%. Median time to remission was 2.6 months (1.3–5.1 months), median time to progression was 4.9 months (95%CI, 2.6–6.7 months), and overall survival was 13,2 months (95% CI, 8.7–16.7 months). Grade 3–4 leucopenia (NCI-CTC) was observed in 64%, neutropenia in 51%, thrombocytopenia in 49%, and anemia in 10% of pts. Conclusion: Gemcitabine plus carboplatin is an effective and well tolerated treatment option in intensively pretreated breast cancer pts. No significant financial relationships to disclose.
Low tumor cell detection rate in bone marrow of patients with primary breast cancer after elimination of stroma cells: Comparison of immunocytology and molecular analysis of CK19 and mammaglobin 1
Authors: Kaul S. , Aggarwal M. , Eichler A. , Sohn C. , Fersis N. 
Published: March 2020

1075 Background: Rapidly self-renewing stroma cells of the bone marrow (RS cells) are MUC-1 and cytokeratin positive at a rate of 56% (475/850). Elimination of RS cells by size exclusion results in a positivity rate of 2.6% (36/1407) in primary breast cancer patients. We have used preanalytical immunomagnetic tumor cell enrichment followed by molecular detection of CK19 and Mammaglobin1 (MA) transcripts for an independent verification of the bright-field immunocytology results. Material and Methods: Mononuclear cells (2x106) from bone marrow of 1,407 patients with primary breast cancer were analysed by standardized cytospin immunocytology techniques. Disseminated tumor cells (DTC) were stained with CK8/18/19 antibodies 5D3 and A45-B/B3 using either the APAAP technique (Dako Techmate 500) or the enhanced SA-FastRed method (Ventana). Parallel DTC consisted of immunomagnetic tumor cell selection of 1x107 BM cells using the cell membrane glycoproteins EpCAM and MUC-1 as targets. CK 19 and MA transcripts were determined by conventional and quantitative real time RT-PCR. Results: Using acetic acid and periodate blocking steps before immunocytology 36 from 1407 (2.6%) breast cancer patients operated between 1999 and 2005 at the University Hspital Heidelberg were scored DCT positive using computer assisted automated (Chromavision ACIS II) picture analysis. From this group 186 bone marrow samples were used for molecular tumor cell detection. By RT-PCR analysis of 1x107 immunomagnetically purified BM cells only 6 from 186 (3.2%) samples were CK19 and MG positive. Discussion: Detection rates of tumor cells in bone marrow from non-metastatic breast cancer patients has been reported to be in the range of 0% to 100%. We show here that proliferating bone marrow stroma cells of the RS type are positive for various antigens including CK polypeptides 7, 8, 18 and 19. Elimination of these cells by size exclusion results in a tumor cell detection rate of 2,6% in 1,407 BM probes. This low detection rate could be verified in 186 BM probes by CK19 and mammaglobin1 RT-PCR. We conclude that standard immunocytology in bone marrow is severely impaired by cytokeratin expression of RS-type stroma cells. No significant financial relationships to disclose.
A phase I trial of pegylated liposomal anthracycline and lapatinib (L) combination in the treatment of metastatic breast cancer (MBC): First evaluation of an anthracycline and lapatinib combination in the treatment of MBC
Authors: Cianfrocca M. E. , Rosen S. T. , von Roenn J. H. , Rademaker A. W. , Rubin S. D. , Friedman R. A. , Rozario C. P. , Gradishar W. J. 
Published: March 2020

1079 Background: Liposomal formulations such as pegylated liposomal doxorubicin (PLD) were developed to improve the therapeutic index and overall benefit of the anthracyclines (A). L is a selective and highly competitive inhibitor of ErbB1 and ErbB2 tyrosine kinases. The combination of conventional doxorubicin and an ErbB2 targeting agent (trastuzumab), while effective, led in a randomized phase III trial to an unacceptable risk of cardiac toxicity. The combination of PLD and L however may be effective with less cardiac risk Methods: This is an open-label, phase I, dose-escalation trial of PLD at 20, 30, 45 and 60 mg/m2 IV every 4 weeks (maximum of 8 doses) and L, 1,500 mg po daily until progression in patients (pts) with MBC. EGFR and/or ErbB2 positivity was not required. Prior chemotherapy, endocrine therapy and trastuzumab were allowed however prior A use was limited to 240 mg/m2 of doxorubicin or 600 mg/m2 of epirubicin and prior EGFR targeting therapies were not allowed. Concomitant CYP3A4 inducers/ inhibitors were not allowed. A left ventricular ejection fraction (LVEF) of ≥ 50% was required. The primary objective was to evaluate the safety, tolerability and feasibility of the combination of PLD and L, particularly with respect to cardiac safety. MUGAs were performed at entry and every 8 weeks thereafter. Results: 7 patients (PLD: 20 mg/m2 - 3 pts; 30 mg/m2 - 3 pts; and 45 mg/m2 - 1 pt) with a mean age of 43 yrs (range, 33–68) have been treated for a total of 14 treatment cycles. Dose-limiting toxicity (DLT) has not been reached. One pt experienced an LVEF drop to < 50% after 4 cycles however this was accompanied by a pericardial effusion felt to be secondary to progressive disease. Adverse events observed include: grade III/IV- none; grade I/II in ≥2 pts- rash, nausea, and anorexia; grade II leukopenia, fatigue, alopecia, diarrhea, headache were also seen in 1 pt each. Preliminary response data in 4 evaluable pts reveals 1 PR, 1 SD, and 2 PD. Conclusions: In the first 7 pts treated, the combination of PLD and L has been well tolerated. One pt experienced an LVEF drop to < 50%, however this was felt likely to be disease-related. DLT has not yet been reached and accrual is ongoing. No significant financial relationships to disclose.
Triple-negative metastatic/recurrent breast cancer: Treatment with paclitaxel/carboplatin combination chemotherapy
Authors: Chia J. W. , Ang P. , See H. , Wong Z. , Soh L. , Yap Y. , Wong N. 
Published: March 2020

1086 Background: Patients with triple negative (ER, PR, Her2 negative) breast cancers do not derive benefit from Herceptin or hormonal agents. For them, conventional chemotherapy remains the only option. Recent data suggests that triple negative breast cancers (TNBC) have increased sensitivity to platinum agents. We conducted a retrospective analysis to determine the response rates of such patients treated with paclitaxel and carboplatin (TC) chemotherapy. Methods: Patients with metastatic/recurrent TNBC were included in our study. Chemotherapy administered at weekly (paclitaxel 80mg/m2 and carboplatin AUC2 on D1, D8, D15) or 3 weekly intervals (paclitaxel 175mg/m2 and Carboplatin AUC 5 on D1). ER and PR status was defined using IHC. Her 2 positive was defined by a positive FISH or 3+ IHC staining. Results: 101 patients with TNBC were diagnosed at our centre from 2002 to 2005 and of these only 23 patients had metastatic/ recurrent disease. 14 patients were treated with TC and therefore included in our analysis. Median age of patients was 53 yrs (range 36 to 68yrs). 3 patients had metastatic disease at diagnosis and 11 patients were treated for recurrent disease. Median time to recurrence for this subgroup was 20 months (range 8 to 224mths). 4 and 6 patients had prior adjuvant exposure to taxanes and anthracyclines respectively. Median prior lines of chemotherapy was 1 (range 0–4). Median number of disease sites in patients was 4. Eight patients (57%) experience a partial response (PR) with TC. 2 patients had stable disease and 4 progressive disease. Although no patients experienced complete response, 3 patients had good PR. One patient with metastatic disease had complete resolution of a large, 9cm locally invasive breast tumor after 3 cycles of TC. The second had a 90% reduction in volume of a large chest wall recurrence after 2 cycles TC. Patients who had 2 or 3 prior lines of chemotherapy also continued to show response. The median time to tumor progression was 16 weeks (range 4–28 wks). Conclusions: TC gives a high response rate in patients with metastatic/ recurrent TNBC. Patients with prior exposure to taxanes and those with large volume disease showed good response. Randomised trials are underway to compare the TC regimen with non-platinum containing doublets. No significant financial relationships to disclose.
Phase II trial of vinorelbine (V) days 1+8 every 3 weeks and trastuzumab (T) weekly as first-line chemotherapy for HER2+ metastatic breast cancer (MBC)
Authors: Andersson M. , Nielsen D. , Sørensen P. G. , Ewertz M. 
Published: March 2020

1091 Background: Weekly V and T as 1. line therapy in patients (pts) with HER2+ MBC is highly effective with reported response rates (RR) from 61–86% and median time to progression (TTP) 8.5–16 months. This study examined V given twice every 3 weeks. Methods: Eligible pts had HER2+ (IHC 3+ or FISH) MBC with measurable disease by RECIST criteria, no prior chemotherapy or T for MBC, and LVEF > 50%. They received V 35 mg/m2 i.v. days 1+8 every 3 weeks (= 1 cycle) and T weekly (4 mg/kg loading dose, 2 mg/kg thereafter i.v.) until progression or unacceptable toxicity. Planned sample size was 50, but the study was replaced by a randomised trial at 46 pts, all of them eligible. Primary endpoint was RR, secondary endpoints included TTP, overall survival (OS) and toxicity. Results: From December 2001-July 2004 46 pts were recruited at 4 centers. They received 11 (1–54) cycles (median, range). V dose was reduced due to neutropenia in 7.5% of cycles and for other reasons in 14.5%. V treatment was delayed due to neutropenia in 7.8% of cycles and for other reasons in 4.7% of cycles. Median received V dose intensity was 0,78. Cardiotoxicity: asymptomatic reduction of LVEF > 20% or >10% to below 50%: 8 pts (3 to below 50%). Toxicity grade III-IV (pts): Neutropenia: 11. Infections: 5 (one septic death). Constipation 2. 43 pts have progressed and 32 have died. RR: CR: 9 (20%) PR: 13 (28%) SD 11 (24%) (SD> 6 months 9 (20%)) PD: 10 (22%) NE: 3 (7%). Median duration of response: 18.0 months. Median TTP: 11.0 months (95% confidence interval (95%CI) 7.6–14.4). Median OS: 25.4 months (95%CI 22.7–28.0). After progression 24 received docetaxel, 14 capecitabine, 6 epirubicine, and 11 endocrine therapy. Conclusions: V given twice every 3 weeks and T weekly is a highly active and well-tolerated 1. Line treatment for HER2+MBC. Recruitment into the trial was stopped at 46 pts in favor of a phase III-trial which is ongoing in the Nordic countries comparing V (days 1+8) + T with docetaxel+T every 3 weeks. No significant financial relationships to disclose.