bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-08-05: A phase I trial of chemotherapy followed by infusions of activated T cells armed with anti-CD3 and anti-HER2 bispecific antibody for stage III, Her2+ or Her2- breast cancer
Authors: Dillon P , Rathore R , Thakur A , Colvin G , Kouttab N , Lum L 
Published: February 2018

Abstract
Background: The balance in the immune system between immune surveillance and tolerance is known to be associated with the prognosis of breast cancer patients. The aim of this phase I study was to assess the safety of anti-CD3 x anti-HER2Bi bispecific antibody targeted (BAT) activated T cells (TC) in high risk breast cancer patients. The BAT T-cells exhibit anti-HER2 cytotoxicity, proliferate, and secrete immunokines upon tumor engagement.
Methods: High risk adjuvant breast cancer patients were recruited and completed standard adjuvant chemotherapy. BATs were produced by stimulating peripheral blood mononuclear cells (PBMC) obtained by leukapheresis; collected TC were then activated with anti-CD3 monoclonal antibody and expanded in IL-2 for 12-14 days. TC were armed with bispecific antibody and cryopreserved until used. Groups of 3 patients received 20, 40, 80 or 160 x 109 BATs per infusion twice a week for four weeks. All patients were treated at Roger Williams Medical Center.
Results: Nine patients were accrued and all had N3 disease. Eight of 9 patients were ER positive; 2 of 9 were HER2 overexpressing. The median OS has not reached as five of nine patients are still alive. OS range from 14.3 to 154.7 months (as December 11, 2016). Five out of the five patients who are alive have no evidence of disease and 1 patient had a secondary primary that has been successfully treated and she has no evidence of disease. It was feasible to grow up to 160 x 109 BATs and this dose level was tolerable without any cell-based dose limiting toxicities. BATs persisted in the blood for at least a week. BAT infusions induce cellular anti-tumor responses and cytokine responses.
Conclusion: Targeting HER2 positive and negative tumors induced cytotoxic anti-tumor responses, increases in Th1 cytokines and IL-12 serum levels. The prolonged survival in a high risk population suggests that BAT infusions provided a clinical benefit. These results are being confirmed in a phase II trial for metastatic breast cancer.
Citation Format: Dillon P, Rathore R, Thakur A, Colvin G, Kouttab N, Lum L. A phase I trial of chemotherapy followed by infusions of activated T cells armed with anti-CD3 and anti-HER2 bispecific antibody for stage III, Her2+ or Her2- breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-08-05.
Abstract P1-09-01: A phase 1b study of abemaciclib plus pembrolizumab for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC)
Authors: Rugo HS , Kabos P , Dickler MN , John WJ , Smith I , Lu Y , Young S , Tolaney SM 
Published: February 2018

Abstract
Background: Abemaciclib is a selective and potent small molecule inhibitor of CDK4 and 6, with evidence of single-agent antitumor activity, and a safety profile that enables dosing on a continuous schedule. Abemaciclib demonstrated anti-tumor activity as a single agent with a 19.7% objective response rate for women with previously treated HR+, HER2- MBC1. In the phase 1b study JPBH, abemaciclib demonstrated a tolerable safety profile when combined with endocrine or HER2 targeted agents for MBC2. Abemaciclib given BID in combination with pembrolizumab also demonstrated a tolerable safety profile in phase 1b study of stage IV NSCLC3.
Methods: JPCE is a multicenter, nonrandomized, open-label, phase 1b study of abemaciclib plus pembrolizumab for patients with HR+, HER2- MBC or NSCLC (ClinicalTrials.gov NCT02779751). The study has 3 disease-specific cohorts, each with approximately 25 patients (N=75); the HR+, HER2- MBC cohort (part C) will be presented here. The primary objective was to characterize safety of the abemaciclib and pembrolizumab combination. Secondary objectives included efficacy endpoints (objective response rate, disease control rate, duration of response, progression-free survival, and overall survival), pharmacokinetics of abemaciclib plus pembrolizumab, and changes in patient-reported pain and disease-related symptoms. Patients received 150 mg of abemaciclib orally Q12H plus pembrolizumab 200 mg as a 30-minute IV infusion on Day 1 every 21 days. Eligible patients included women with confirmed HR+, HER2- MBC who have previously received at least 1 but no more than 2 prior chemotherapy regimens for MBC; are able to provide tumor tissue at baseline and at cycle 3, day 1; have measurable disease (RECIST v.1.1), adequate organ function, ECOG PS ≤1, are able to swallow oral medications; and have not received treatment with CDK4 & 6 or PD-1/ PD-L1 inhibitors.
Results: At the time of abstract submission, study JPCE part C cohort (HR+, HER2- MBC) was fully enrolled at 25 patients. Data to be presented include patient demographics, baseline disease characteristics, adverse events by frequency and by grade, and preliminary efficacy of the abemaciclib plus pembrolizumab combination in HR+, HER2- MBC.
References:
1. Dickler et al, Clin Cancer Res. 2017
2. Goetz et al. poster presented at SABCS, 2015
3. Goldman et al. poster presented at IASLC 2016
Citation Format: Rugo HS, Kabos P, Dickler MN, John WJ, Smith I, Lu Y, Young S, Tolaney SM. A phase 1b study of abemaciclib plus pembrolizumab for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-09-01.
Abstract P1-10-16: In vitro delivery of model fluorescent dyes through the mammary papilla
Authors: Kurtz SL , Lawson LB 
Published: February 2018

Abstract
In the United States, 100,000 women each year are diagnosed with atypical hyperplasia (AH), significantly increasing their risk of developing breast cancer. However, only 40% of patients accept breast cancer preventive treatment, in part, due to systemic side effects. The localization of pre-cancerous cells within the ducts or lobules of the breast permits a local treatment strategy employing the innate mammary ducts. This expansive tree-like structure extends throughout the entire breast and may serve as a conduit for local delivery of therapeutics, thereby minimizing side effects associated with current preventive treatment strategies. This study examines how lipophilicity influences diffusion through porcine tissue using a model hydrophilic dye, Sulforhodamine B (SRB), and a model lipophilic dye, Nile Red (NR). Porcine nipple or skin tissue was positioned in a Franz diffusion cell and the formulations were applied topically. With equivalent dye concentrations applied to the donor surface, we noted no significant difference in total dye permeation when comparing diffusion through skin versus nipple tissue or when comparing SRB versus NR after 48 hours. However, the diffusion coefficient for both NR and SRB through the nipple was almost 700-fold greater compared to through the skin indicating improved drug delivery via the nipple. Additionally, after 48 hours there was significantly higher retention of SRB in the nipple and skin compared to NR. When we further looked at the distribution of each dye within the nipple using fluorescence microscopy, we saw a distinction in the localization of each dye. Fluorescence micrographs show that lipophilic NR is retained within the ducts while the hydrophilic SRB diffuses throughout the entire tissue section, suggesting that hydrophobicity impacts the ability of molecules to diffuse from the duct into the surrounding tissue. This suggests that lipophilic carriers may be effective for delivery of cancer therapeutics or preventative agents targeting the mammary ducts, where AH is localized.
Citation Format: Kurtz SL, Lawson LB. In vitro delivery of model fluorescent dyes through the mammary papilla [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-16.
Abstract P1-12-01: Withdrawn
Authors: Bardia A , Vahdat LT , Diamond JR , Kalinsky K , O'Shaughnessy J , Moroose RL , Isakoff SJ , Tolaney SM , Santin AD , Abramson V , Shah NC , Govindan SV , Maliakal P , Sharkey RM , Wegener WA , Goldenberg DM , Mayer IA 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P1-16-01: Tumor subtype concordance between breast and bone biopsies in bone only metastasis patients
Authors: Parkes AM , Clifton KK , Al Awadhi A , Oke OC , Warneke CL , Litton JK , Hortobagyi GN 
Published: February 2018

Abstract
Background:
Bone is the most common site of metastasis in metastatic breast cancer patients. Notably, bone biopsy is considered technically challenging with concerns regarding yield and reproducibility of immunohistochemistry technique. Our goal was to assess tumor subtype concordance between breast and bone biopsies done in patients with bone only metastases.
Methods:
We identified patients followed at MD Anderson Cancer Center for at least 6 months from 01/01/1997 to 12/31/2015 with bone as first site of metastasis. Breast and bone biopsy immunohistochemistry was used to categorize tumor subtype with hormone receptor positive (HR+) defined as ER or PR &gt;1%. The following four tumor subtypes were identified: luminal A-like (HR+, HER2-), luminal B-like (HR+, HER2+), triple negative (HR-, HER2-), and HER positive (HR-, HER2+).
Results:
We identified 805 bone only metastasis patients with positive bone biopsies, 395 (49%) of which had hormone receptor and HER2 characterization available. Of these 395 patients, 293 (74%) were luminal A-like, 44 (11%) were luminal B-like, 51 (13%) were triple negative, and 7 (2%) were HER2 positive. Of these patients, we identified 281 patients with tumor subtype data available for both primary breast biopsy and bone metastasis biopsy, of which 237 (84%) were concordant, while 44 (16%) were discordant (Table 1).
Table 1. Concordance between breast and bone biopsies based on initial breast biopsy tumor subtypeBreast Biopsy Tumor Subtype (n = 281)Concordance with Bone Biopsy Tumor SubtypeDiscordant Bone Biopsy Tumor SubtypeLuminal A-like, HR+ HER2- (225/80%)Concordant: 199 (88%), Discordant: 26 (12%)10 Luminal B-like, 16 Triple negativeLuminal B-like, HR+ HER2+ (33/12%)Concordant: 19 (58%), Discordant: 14 (42%)11 Luminal A-like, 2 Triple negative, 1 HER2 positiveTriple negative, HR- HER2- (20/7%)Concordant: 16 (80%), Discordant: 4 (20%)3 Luminal A-like, 1 Luminal B-likeHER2 positive, HR- HER2+ (3/1%)Concordant: 3 (100%), Discordant: 0 (0%)NA
Conclusions:
When available, bone biopsy tumor subtype had significant concordance with breast biopsy tumor subtype in this large study of bone only metastasis patients. Discordant tumor subtype results were more common in patients with luminal B-like tumor subtype on initial breast biopsy.
Citation Format: Parkes AM, Clifton KK, Al Awadhi A, Oke OC, Warneke CL, Litton JK, Hortobagyi GN. Tumor subtype concordance between breast and bone biopsies in bone only metastasis patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-16-01.
Abstract P1-17-08: Efficacy of lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive metastatic breast cancer: A systematic review and meta- analysis
Authors: Thein KZ , Zaw MH , Yendala R , Igid HP , Chai-Adisaksopha C , Hardwicke F , Awasthi S , Radhi S 
Published: February 2018

Abstract
Background:
Brain metastases contribute to significant morbidity and mortality in breast cancer. Approximately one fourth of breast tumors overexpress the human epidermal growth factor receptor 2 (HER2) protein and are twice as likely to develop brain metastases. There are currently no systemic therapies approved. We undertook a systematic review and pooled analysis of trials to determine the efficacy of lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive metastatic breast cancer (MBC).
Methods:
We performed a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts through December 31, 2016. Trials that utilized lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive MBC were incorporated in the analysis. The pooled estimated rates were calculated using random effects model. Heterogeneity was assessed using I2 statistic.
Results:
A total of 513 patients with brain metastases from HER-2 positive MBC from 6 trials and a subgroup of another 4 trials were included in our analysis. Lapatinib and capecitabine therapy was used as second-line treatment in 9 studies (n= 468) and as first-line treatment in the LANDSCAPE study (n= 45). Three studies were retrospective evaluations of randomized trials and the rest were phase 2 trials. CNS objective response rate (ORR) was 26% (95% CI: 19 – 33, I2: 65.9%). Complete response (CR) rate was 1% (95% CI: 0 - 2, I2: 0.0%) and partial response (PR) rate was noted at 24% (95% CI: 17- 31, I2: 66.1%). Stable disease (SD) occurred in 37% (95% CI: 29- 45, I2: 66.6%) and progressive disease (PD) in 19% (95% CI: 12- 25, I2: 66.5%). The first line LANDSCAPE study had the highest PR (49%) and ORR (53%) without a significant impact on CR rate; PD was 7%.
Conclusion:
Brain metastases in breast cancer is an area of urgent unmet need. Our meta-analysis showed that lapatinib/capecitabine therapy had some first line or second line activity in brain metastases from HER-2 positive MBC. Nevertheless, further randomized controlled trials are required in this patient population.
Citation Format: Thein KZ, Zaw MH, Yendala R, Igid HP, Chai-Adisaksopha C, Hardwicke F, Awasthi S, Radhi S. Efficacy of lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive metastatic breast cancer: A systematic review and meta- analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-17-08.
Abstract P2-01-07: Isolation of viable CTCs from leukapharesis product with parsortix system enables subsequent culture
Authors: Neubauer H , Franken A , Driemel C , Lampignano R , Behrens B , Reinhardt F , Niederacher D , Stoecklein NH , Fischer JC , Fehm T 
Published: February 2018

Abstract
Background: Solid tumors are constantly releasing circulating tumor cells (CTCs) into the circulatory system. They are genotypically and phenotypically different from the primary tumor. Especially viable CTCs can be of high interest to obtain further therapeutically relevant information. Their extremely low frequency is one of the main limiting factors to use them for further characterization.
To overcome this challenge we tested to isolate viable CTCs from diagnostic leukapharesis (DLA) products obtained from breast cancer patients.
Material/methods: 16 DLA samples and matched peripheral blood (PB) samples of metastasized breast cancer patients were collected and CTC numbers were determined by CellSearch® analysis. Viable cells were enriched from DLA product with Parsortix system. Genomic DNA of single cultured CTCs was isolated and amplified by whole genome amplification. Array-based comparative genomic hybridization of single cells was performed to analyze for genomic aberrations. Resulting profiles were compared to genomic aberration profiles of CTCs isolated before in vitro culture.
Results: CTCs were detected in ten PB and matched DLA samples and in three more DLA samples whose corresponding blood samples were CTC-negative. CTC number per ml was increased by an average of 22.5 fold. Parsortix was optimized to enrich tumor cells from DLA product while keeping them best viable. An enrichment rate of 67.7% ± 11.3% and a harvesting rate of 65.3% ± 9.7% were determined with spiked MCF7 cells. We could grow viable CTCs from three out of eight CTC positive DLA samples from metastasized patients as determined by immune fluorescence analysis. The growing cells harbor genomic anomalies confirming their malignant origin. Most aberrations are widely identical to the aberrations detected in uncultured CTCs.
Conclusions: DLA provides greater numbers of viable CTCs which can be enriched with Parsortix system in order to enable their in vitro cultivation. This workflow will allow functional studies.
Citation Format: Neubauer H, Franken A, Driemel C, Lampignano R, Behrens B, Reinhardt F, Niederacher D, Stoecklein NH, Fischer JC, Fehm T. Isolation of viable CTCs from leukapharesis product with parsortix system enables subsequent culture [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-01-07.
Abstract P2-02-13: Utilization of cell-free circulating tumor DNA for management of breast cancer: Practices in academic and community oncology
Authors: Thomas RA , Klar N , Kiedrowski L , Nagy RJ , Lee AV , Brufsky A 
Published: February 2018

Abstract
Background: Next-generation sequencing (NGS) of cell-free DNA (cfDNA) is increasingly being utilized to assess somatic genomic alterations in patients with breast cancer. We investigated the clinical use of such testing in breast cancer care in a major healthcare system with both academic and community-based practices. We also explored the observed genomic landscape in the analyzed patient cohort and whether treatment plans were modified based on the results.
Methods: A retrospective review of cfDNA NGS results (Guardant360) ordered at the University of Pittsburgh Medical Center for patients with breast cancer from 7/2015-3/2017 was performed. Test ordering patterns, the landscape of genomic alterations identified, and clinical use of select results were assessed.
Results: During this period 95 samples were submitted, 73 (77%) ordered by academic center providers and 22 (25%) from community providers. Alterations were detected in 88 samples (93%) with a median of 3 alterations per test. Five patients had serial samples ordered assessing dynamic cfDNA across clinical treatment and progressions, leaving 84 unique patients in the dataset. The average patient age was 57, and 95% of patients were female. Patients were most often observed to have alterations in TP53 (51%), PIK3CA (44%), and ESR1 (26%). Additional clinical data were collected for 48 patients with mutations or amplifications in PIK3CA, ESR1, and/or ERBB2 (HER2) to assess for clinical use of genomic information. Results were used to change clinical care in 13 (27%) of these cases. Community providers were more likely to use genomic results to guide clinical management in these cases (9/16, 56%) than academic providers (4/32, 12.5%), p=0.001. Of this patient subset, those with tests ordered by an academic provider had more lines of prior therapy at the time of testing vs. those in the community (average 5.9 vs 3.4 respectively, p=0.019).
Conclusions: CfDNA NGS analysis for somatic genomic alterations in breast cancer is being ordered clinically by both academic and community practices within this healthcare system. Results for a subset of clinically annotated patients were acted on more frequently by community-based ordering providers, which may be related to patients tested at academic sites having had more lines of prior treatment.
Citation Format: Thomas RA, Klar N, Kiedrowski L, Nagy RJ, Lee AV, Brufsky A. Utilization of cell-free circulating tumor DNA for management of breast cancer: Practices in academic and community oncology [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-02-13.
Abstract P2-04-07: Triple negative breast cancer-specific chromatin conformation links Notch signal to tumor-specific transcriptional program
Authors: Petrovic J , Zhou Y , Georgakilas G , Vahedi G , Pear WS , Faryabi RB 
Published: February 2018

Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is currently incurable with conventional chemotherapy. Some TNBC patients harbor either recurrent somatic gain-of-function mutations or focal amplification in genes coding for Notch receptors. Recent findings suggest that Notch signals, in the absence of Notch mutations are also important to maintain chemotherapy-resistant circulating tumor cells. Importantly, elevated Notch signaling is specifically enriched in the TNBC and is associated with worse survival in this subtype. These findings underscore the importance of Notch signaling in pathogenesis of TNBC and suggest potential new avenue for therapeutic approaches. Despite this, the target genes and oncogenic mechanisms downstream of aberrant Notch signaling are poorly understood. To create a high confidence map of the oncogenic Notch-driven regulome in TNBC, we performed an integrative, comprehensive and functional genome-wide analysis of Notch-driven targets in Notch-mutated TNBC cell lines by combining high-resolution genome-wide chromatin topology data (HiChIP), dynamic mapping of Notch transcriptional complex members and active and repressive chromatin marks (ChIP-seq), as well as evaluation of dynamic transcription (RNAseq) in presence and absence of Notch signals. One important oncogene and critical Notch target in TNBC is MYC. Our integrative analysis identified detailed map of Notch-dependent MYC regulatory network. The TNBC-specific MYC regulatory region, located 5' of MYC, is much more complex compared to other known Notch-driven malignancies and constitutes of a broad domain of active enhancers marked by H3K27ac that are not present in Notch-driven lymphoma and leukemia. Integrative analysis of ChIP-seq and HiChIP revealed multiple enhancers within this broad domain of regulatory elements that are directly bound by the members of Notch transcriptional complex, sensitive to acute changes in Notch activation and that contact MYC promoter via tumor specific chromatin loops. We showed that genetic perturbation of MYC by CRISPR/Cas9 approach was sufficient to kill TNBC cells. Since, MYC is difficult to target pharmacologically an alternative strategy is to use drugs that inhibit factors regulating MYC expression. To this end, elucidating the Notch regulatory landscape, and in particular, the mechanism by which Notch regulates MYC expression in TNBC may reveal new therapeutic strategies to precisely target MYC in Notch-dependent breast cancer.
Citation Format: Petrovic J, Zhou Y, Georgakilas G, Vahedi G, Pear WS, Faryabi RB. Triple negative breast cancer-specific chromatin conformation links Notch signal to tumor-specific transcriptional program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-04-07.