bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES9-3: Androgen, progesterone and glucocorticoid receptors: Drivers of breast tumor progression or reprogramming of steroid receptors during breast tumor progression
Authors: Conzen SD 
Published: February 2018

Abstract
In normal physiology, glucocorticoid receptor (GR) activity regulates thousand of genes whose products modulate metabolism, inflammation, cell cycle and apoptosis/cell survival pathways. Synthetic GR agonists, or glucocorticoids (GCs), are often used to treat hematologic malignancies because of GR's ability to induce proapoptotic gene expression, inhibit nuclear factor – κB, and induce cell cycle arrest. In contrast, recent examination of GR expression and activity in human breast cancer models and clinical specimens has suggested that GR expression has remarkably diverse roles in breast cancer subtypes. In ER+ breast cancer, GR appears to modulate ER-regulated transcriptional activity through ER/GR receptor crosstalk resulting in antagonism of ER-associated proliferation. However, in ER-negative breast cancer (including TNBC), high tumor GR expression is associated with poor prognosis, anti-apoptotic signaling, and chemotherapy resistance. In addition, high GR activity in the tumor microenvironment is predicted to be immunosuppressive. Recently described selective GR modulators are expected to help dissect divergent GR mechanisms present in breast cancer subtypes.
Citation Format: Conzen SD. Androgen, progesterone and glucocorticoid receptors: Drivers of breast tumor progression or reprogramming of steroid receptors during breast tumor progression [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 ES9-3.
Abstract MS2-2: Understanding the unique biology of ILC
Authors: Oesterreich S 
Published: February 2018

Abstract
Invasive lobular breast cancer (ILC) is characterized by distinct etiological, pathological, and clinical features, yet the underlying biology is poorly understood. To extend the molecular determinants of ILC beyond the well-known loss of E-cadherin, we combined a plethora of in silico and wet-bench approaches, and comprehensively characterized ILC tumor models and clinical samples.
In support of recent data from The Cancer Genome Atlas on differences in mutations in critical ER co-factors between invasive lobular and ductal cancers, we have identified distinct ER signaling pathways, and mechanisms of endocrine resistance in ILC. These include the acquisition of unique ER target genes, activation of IGF and FGFR signaling, and changes in metabolic pathways. As part of our efforts to elucidate mediators of ILC progression, transcriptomic analysis of primary tissue from patients with and without disease recurrence identified potential genetic drivers, including Cortactin, an actin binding protein with a known role in metastasis. To further identify genes that mediate the unique metastatic properties of ILC cells, we sequenced metastases to the ovary and the gastrointestinal tract, and uncovered pathways that might serve as critical vulnerabilities and therapeutic opportunities. In this lecture, I will review our progress, and discuss the potential clinical significance and implications of these findings.
Citation Format: Oesterreich S. Understanding the unique biology of ILC [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 MS2-2.
Abstract OI-1: Tackling Breast Cancer Diversity
Authors: Turner NC 
Published: February 2018

Abstract
Breast cancer is a highly diverse disease with multiple subtypes and driver mutations. Further diversity may develop, particularly in metastatic breast cancer, due to the selective pressure of treatment. In ER positive breast cancer, activating mutations of the oestrogen receptor (ESR1), along with mutations in the NF1, KRAS and FGFR genes, are all enriched in endocrine resistant breast cancer, although rare in untreated primary breast cancer.
This diversity presents a substantial challenge to the treatment of metastatic breast cancer, with new therapeutic approaches required to tackle this heterogeneity. Circulating tumour DNA analysis, to identify selected mutations in the tumour and guide matching targeted therapy, has preliminary evidence of clinical utility. Targeting common phenotypes presents an alterative therapeutic approach, targeting the dependence of luminal breast cancer on CDK4/6 to initiate cell cycle entry. Pre-clinical evidence supports combining CDK4/6 inhibition with mutation-targeted therapies, although implementing these combinations presents a substantial clinical translational challenge.
A novel approach to overcoming tumour heterogeneity is to identify and target micro-metastatic cancer in the adjuvant setting. Micro-metastatic cancer can be detected with highly sensitive circulating tumour DNA analysis for minimal residual disease (MRD) detection. This may open up a new paradigm of treatment guided by MRD monitoring, potentially treating cancer in a setting where the cancer may be less genetically diverse, with lower potential to develop resistance to therapy.
Citation Format: Turner NC. Tackling Breast Cancer Diversity [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 OI-1.
Abstract OT2-01-05: Sentinel lymphnode biopsy (SLNB) and targeted axillary surgery (TAS) by indocyaningreen (ICG) and a novel near-infrared color camera system - a prospectively randomised, multicenter study to avoid radioactivity in a time-/cost-saving procedure in primary breast cancer
Authors: Kern P , Kimmig R , Rezai M , Hoffmann O , Bücker I , Braun M 
Published: February 2018

Abstract
Background: Sentinel lymph node biopsy (SLNB) by radioactively labelled 99mTechnetium +/- patent blue is so far the current standard in SLN detection. However, it remains a time- and cost-consuming procedure requiring the availability of a nuclear medicine department and a precise coordination with the subsequent surgery. It could be desirable to empower surgeons to be independent from availability of a nuclear source and to spare patients from radioactivity. Indocyanine green (ICG) as a fluorescent coloring agent is already known as safe in diagnostics for heart, circulation, liver and eye disease and may represent a valid alternative to 99mTc and patent blue (PBD), especially as it does not cause aesthetic impairment of the breast, with ICG being only visible with near infra-red light.
Methods: This prospective, randomized study is a non-inferiority trial to evaluate ICG-fluorescence as an alternative to either 99mTc and/or patent blue dye for sentinel lymph node detection of primary breast cancer with and without neoadjuvant chemotherapy.
Patients, aged 18 - 80 years, with unilateral or bilateral, unifocal or multifocal/ multicentric primary breast cancer without signs of metastases and written consent are eligible for this study. ECOG status of 0-2 and life expectancy &gt; 1 year is required. All BMI classes are admitted to the study, with predefined subgroups of a) &lt;= 20 b) &gt;20-30 c) &gt;30-40 d) &gt;40. Tumor stages included are a) Tis (&gt;= 4 cm) b) T1 c) T2 and d) T3. ICG-guided SLNB may be applied in patients in the following settings: a) before neoadjuvant, b) after neoadjuvant chemotherapy.
Primary Endpoints: Rate of SLN detection by either of the methods in the following 3 arms of the trial:
Arm A: 99mTc + patent blue dye (PBD)
Arm B: 99mTc + indocyanine green (ICG)
Arm C: Indocyanine green (ICG)
Secondary Endpoints:
- Time to identify (TTI) sentinel lymph node(s) (min)
- Number of sentinel lymph nodes (SLN) and non-sentinel lymph nodes (non-SLN)
- Rate of concordance of detection by 99mTc+patent blue dye (PBD) vs. 99mTc + ICG
- Dose of radioactivity omitted in Arm C vs. Arm A & B
Results: This trial is in progress.
Citation Format: Kern P, Kimmig R, Rezai M, Hoffmann O, Bücker I, Braun M. Sentinel lymphnode biopsy (SLNB) and targeted axillary surgery (TAS) by indocyaningreen (ICG) and a novel near-infrared color camera system - a prospectively randomised, multicenter study to avoid radioactivity in a time-/cost-saving procedure in primary 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 OT2-01-05.
Abstract OT2-07-01: Phase 1/2 trial of the oncolytic virus, talimogene laherparpvec, in combination with neoadjuvant chemotherapy in stage II/III triple negative breast cancer
Authors: Soliman HH , Hogue D , Han H , Lee C , Ismail-Khan R , Khong H , Niell B , Czerniecki B 
Published: February 2018

Abstract
Background: The host anti-tumor immune response plays an important role in determining natural history and therapy response for early stage breast cancer. Tumors with high levels of lymphocytic infiltration appear to have a superior prognosis and response rate to neoadjuvant chemotherapy. However, these tumors are in the minority so methods to enhance tumor lymphocyte infiltration should be identified. The oncolytic virus, talimogene laherparpvec (TVEC) is a genetically modified HSV1 virus which selectively replicates in transformed cells while sparing normal tissue. This leads to lysis of infected tumor cells along with co-expression of GM-CSF to elicit an enhanced anti-tumor immune response. Prior data has shown TVEC can be safely combined with chemotherapy in other indications, so we launched an investigator initiated study to determine the safety and efficacy of combining TVEC with neoadjuvant dose dense chemotherapy in stage II-III TNBC.
Study design: The study is a phase 1 (2 dose levels of TVEC, 3+3 design) and phase 2 single arm Simon two stage combination trial. Primary endpoints of phase 1 is safety of intratumoral TVEC (DL1=106 PFU x 5 injections, DL2=106 PFU x 1 then 108 PFU x 4 injections) administered q2-3 weeks concurrently with weekly paclitaxel followed by standard dose dense AC x 4 and local therapy as indicated. Phase 2 primary endpoint is pCR rate of the study treatment, secondary endpoints include DFS, OS, immune correlates in resected tumor specimens. Eligibility criteria includes females &gt;17 years old, newly diagnosed T2-3N0-3 TNBC, adequate organ function, primary tumor amenable to injection with TVEC, no immunosuppressive or autoimmune conditions, no inflammatory or bilateral/multifocal disease. Sample size is up to 49 patients (12 phase 1, 37 phase 2) with 80% power to detect increase in pCR rate from 30% to 50% with one sided p=.1 in phase 2.
Study status: This novel Amgen supported investigator initiated study activated to accrual 3/2017 and first patient on study was on 5/2017. The study is currently open only at the Moffitt Cancer Center. Target study completion date 8/2021. (NCT02779855)
Citation Format: Soliman HH, Hogue D, Han H, Lee C, Ismail-Khan R, Khong H, Niell B, Czerniecki B. Phase 1/2 trial of the oncolytic virus, talimogene laherparpvec, in combination with neoadjuvant chemotherapy in stage II/III triple negative 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 OT2-07-01.
Abstract OT3-05-11: Palbociclib after CDK inhibitor and endocrine therapy (PACE): A randomized phase II study of fulvestrant versus palbociclib plus fulvestrant, with and without avelumab, for CDK inhibitor pre-treated HR+/HER2- metastatic breast cancer
Authors: Mayer EL , Wander SA , Regan MM , DeMichele AM , Forero A , Rimawi MF , Ma CX , Cristofanilli M , Anders CK , Huang Bartlett C , Koehler M , Winer EP , Burstein HJ 
Published: February 2018

Abstract
Background:
CDK4/6 inhibition (CDK4/6i) has a significant role in contemporary management of hormone receptor positive/HER2 negative (HR+/HER2-) metastatic breast cancer (MBC). The addition of a CDK4/6i to endocrine therapy (ET) in HR+/HER2- MBC leads to prolongation of progression-free survival in previously untreated and pre-treated HR+/HER2- MBC. Mechanisms of resistance to CDK4/6i are not well described, and it is not known if continuation of CDK4/6i with subsequent lines of ET improves outcomes over ET alone. Further, preclinical data suggest combination therapy with ET, CDK4/6i, and anti-PDL1 may provide synergistic efficacy. The PACE trial was designed to determine the optimal subsequent line of therapy in patients (pts) with HR+ /HER2- MBC that has progressed despite prior CDK4/6 inhibition and endocrine therapy.
Methods:
PACE (NCT03147287) is a multicenter phase II trial randomizing pts 1:2:1 to Arm A: fulvestrant alone (with option for Palbociclib (P) monotherapy crossover at time of progression); Arm B: fulvestrant + P; or Arm C: fulvestrant + P + avelumab. The primary objective is to evaluate progression-free survival (PFS) with the combination of fulvestrant + P vs. fulvestrant alone; secondary objectives include overall response (OR), safety and tolerability, and PFS comparisons of avelumab containing arm vs other arms. Exploratory objectives include assessment of outcomes in predefined molecular subgroups (i.e. ESR mutation, PI3K mutation, and loss of Rb); and comparing OR by RECIST vs irRECIST in the avelumab cohort. Extensive molecular profiling of tissue, ctDNA, and CTCs for markers of response and resistance to therapy is also planned. Eligible pts have HR+/HER2- MBC, with prior response to and subsequent progression on any CDK4/6i and ET, defined as at least 6 months of prior treatment, with confirmed subsequent progression, and no more than one prior P dose reduction for toxicity. Pts may have had 1-2 prior ET (aromatase inhibitor or tamoxifen), and 0-1 prior lines of chemotherapy. A sample size of 220 patients is planned.
Citation Format: Mayer EL, Wander SA, Regan MM, DeMichele AM, Forero A, Rimawi MF, Ma CX, Cristofanilli M, Anders CK, Huang Bartlett C, Koehler M, Winer EP, Burstein HJ. Palbociclib after CDK inhibitor and endocrine therapy (PACE): A randomized phase II study of fulvestrant versus palbociclib plus fulvestrant, with and without avelumab, for CDK inhibitor pre-treated HR+/HER2- metastatic 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 OT3-05-11.
Abstract P1-01-15: Investigation of phosphoserine aminotransferase 1 and its role in breast cancer progression
Authors: Metcalf S , Kruer T , Klinge C , Clem B 
Published: February 2018

Abstract
Metastasis and endocrine resistance are two factors that complicate therapeutic intervention in breast cancer patients and lead to poorer overall survival. Metastasis is known to be responsible for 90% of cancer related deaths, and is especially prevalent in triple negative breast cancer (TNBC); while endocrine resistance can affect up to 50% of patients diagnosed with estrogen receptor positive breast cancer (ER+BC). Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second step within de novo serine biosynthesis and increased expression of enzymes in this pathway have been linked to progression of breast cancer and poor clinical outcomes. Within our preliminary retrospective analysis of human breast cancer patients, we identified an inverse association with elevated transcript levels and poorer distant metastasis free survival, which, coupled to a previously reported correlation of PSAT1 with response to endocrine therapy in patients with ER+BC, we postulate that PSAT1 contributes to breast cancer progression through promotion of metastasis and/or endocrine resistance. To initially determine relevance for PSAT1, immunohistochemistry was performed to determine PSAT1 expression in human breast cancer patients. We found that PSAT1 expression is increased through breast cancer progression, with highest levels observed within metastatic conditions. To investigate the metastatic contribution of PSAT1, we silenced PSAT1 expression within the triple negative breast cancer cell line (TNBC), MDA-MB-231. While suppression of PSAT1 had no effect on proliferation, there was a significant decrease in the motility and invasion of these cells. In addition, decreased PSAT1 substantially inhibited lung metastasis following tail-vein injections of MDA-MB-231 cells in vivo. To investigate PSAT1's role in endocrine resistance, we used parental MCF-7 cells and an endocrine-resistant derivative cell line (LY2) and found that LY2-resistant cells exhibited higher PSAT1 expression compared to parental MCF-7 cells. Lastly, suppression of PSAT1 was able to sensitize the LY2 cells to 4-hydroxytamoxifen treatment. Taken together, these data indicate that PSAT1 may contribute to the progression of human breast cancer via either metastasis or endocrine resistance or both and could potentially serve as a viable target for new therapies.
Citation Format: Metcalf S, Kruer T, Klinge C, Clem B. Investigation of phosphoserine aminotransferase 1 and its role in breast cancer progression [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 P1-01-15.
Abstract P1-01-16: Detection of disseminated tumor cells in DCIS patients impacts local recurrence
Authors: Walter VP , Taran F-A , Wallwiener M , Brucker SY , Hartkopf AD 
Published: February 2018

Abstract
Background
Recently it was shown that tumor cell dissemination is an early event in breast cancer progression (Hosseini et al., Nature 2016). This has been backed up by an assessment of over 100,000 patients with in situ carcinoma (DCIS), where some patients developed distant metastases and died from breast cancer without presenting with local invasive recurrence (Narod et al., JAMA Oncology 2015). We therefore analyzed the presence and clinical impact of disseminated tumor cells (DTC) in the bone marrow (BM) of DCIS patients.
Methods
BM aspirates were collected from patients undergoing surgery for primary DCIS at Tuebingen University Hospital between 2001 and 2016. Exclusion criteria were presence of invasive breast cancer, bilateral or metastatic disease as well as other malignancies in their history. DTC were identified by immunocytochemistry using the A45-B/B3 anti-pancytokeratin antibody.
Results
627 patients were included. Median follow-up was 49 months. 72 (11%) had detectable DTC. The detection of DTC was not significantly associated with lymph node positivity (3/479, Fisher's exact test: p=0.307) or tumor size (median 30mm, Wilcoxon test: p=0.952).
In 33 (5%) women, a disease recurrence was observed. Of 31 local recurrences 19 were invasive. 7 Patients developed distant metastases, four without an invasive recurrence beforehand. 14 patients died during follow-up.
The detection of at least 2 DTC per 1.5x106 mononuclear BM cells was significantly associated with a lower local recurrence free survival (log-rank: p=0.023) whereas there was no significant difference in distant disease free survival (p=0.315) and overall survival (p=0.083).
Discussion
For the first time, we were able to show that DTC-detection in DCIS patients is associated with local recurrence.
The number of distant metastases in women without invasive local recurrence detected in this cohort was comparable to earlier findings at different centers. This study warrants further investigations concerning evolutionary relationship between primary tumor, minimal residual disease, local recurrence and clinically detectable macrometastases.
Citation Format: Walter VP, Taran F-A, Wallwiener M, Brucker SY, Hartkopf AD. Detection of disseminated tumor cells in DCIS patients impacts local recurrence [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 P1-01-16.
Abstract P1-02-01: NMR metabolomic signatures reveal predictive plasma metabolites associated with long-term risk of developing breast cancer
Authors: Lécuyer L , Victor Bala A , Deschasaux M , Bouchemal N , Nawfal Triba M , Vasson M-P , Rossary A , Demidem A , Galan P , Hercberg S , Partula V , Le Moyec L , Srour B , Fiolet T , Latino-Martel P , Kesse-Guyot E , Zelek L , Savarin P , Touvier M 
Published: February 2018

Abstract
Background: Combination of metabolomics and epidemiological approaches opens new perspectives for ground-breaking discoveries. The aim of the present study was to investigate for the first time whether plasma non-targeted metabolomic profiles, established from a simple blood draw from healthy women, could contribute to predict the risk of developing breast cancer within the following decade and to better understand the etiology of this complex disease.
Methods: A prospective nested case-control study was set up in the SU.VI.MAX cohort, including 206 breast cancer cases diagnosed during a 13y follow-up, and 396 matched controls. Non-targeted NMR metabolomic profiles were established from baseline plasma samples. Multivariable conditional logistic regression models were computed for each individual NMR variable and for combinations of variables derived by principal component analysis.
Results: Several metabolomic variables from 1D NMR spectroscopy were associated with breast cancer risk. Women characterized by higher fasting plasma levels of valine, lysine, arginine, glutamine, creatine, creatinine, and glucose and lower plasma levels of lipoproteins, lipids, glycoproteins, acetone, glycerol-derived compounds and unsaturated lipids had a higher risk of developing breast cancer. P-values ranged from 0.00007 (ORT3vsT1=0.37[0.23-0.61] for glycerol-derived compounds) to 0.04 (ORT3vsT1=1.61[1.02-2.55] for glutamine).
Conclusion: This study highlighted associations between baseline NMR plasma metabolomic signatures and long-term breast cancer risk. These results provide interesting insights to better understand complex mechanisms involved in breast carcinogenesis and evoke plasma metabolic disorders favorable for carcinogenesis initiation. This study may contribute to develop screening strategies for the identification of at-risk women for breast cancer well before symptoms appear.
Citation Format: Lécuyer L, Victor Bala A, Deschasaux M, Bouchemal N, Nawfal Triba M, Vasson M-P, Rossary A, Demidem A, Galan P, Hercberg S, Partula V, Le Moyec L, Srour B, Fiolet T, Latino-Martel P, Kesse-Guyot E, Zelek L, Savarin P, Touvier M. NMR metabolomic signatures reveal predictive plasma metabolites associated with long-term risk of developing 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 P1-02-01.