bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-01-07: Pre-operative selection of patients with limited disease of the axilla using ultrasonography of the axilla: Might additional lymph node dissection (ALND) be safely omitted in the future?
Authors: Moorman AM , Bourez R , Heijmans HJ , Kouwenhoven EA 
Published: August 2014

Abstract
Background: The sentinel lymph node biopsy (SLNB) procedure is the method of choice for the identification and monitoring of regional lymph node metastases in patients with breast cancer. In the case of a positive sentinel node additional lymph node dissection is still warranted for regional control, though 40-65% have no additional axillary disease. Recent studies showed that after breast-conserving surgery, SLNB and adjuvant systemic therapy there is no significant difference between recurrence-free interval and overall survival if there are 2 or less positive axillary nodes.
Purpose: Preoperative identification of patients with limited axillary disease (≤ 2 macrometastases) using ultrasonography (US).
Method: Between January 2007 and August 2011, data from 1103 consecutive primary breast cancer patients who underwent surgery in our hospital were collected into a single database. Patients were selected by clinical tumours smaller than 50mm (cT1-2), no palpable adenopathy (cN0) and a maximum of 2 SLNs containing macrometastases. The variable of interest was ultrasonography of the axilla. The population was divided into two groups: the group with 2 or fewer positive nodes and the group with more than 2 positive nodes in the axilla after ALND.
Results: After selection, 1060 patients remained of which 102 (9.6%) had more than 2 positive axillary nodes on SLNB or ALND. Selected by unsuspected US, the chance of having more than 2 positive lymph nodes is substantially lower (4.2%). This is significant on univariate and multivariate analysis. The chance of more than 2 positive lymph nodes was 12.8 times as big in case of a positive axillary US. When we select this subgroup even further by excluding the patients with extra capsular extension (ECE) on SLN, the chance of more than 2 positive lymph nodes is only 2.6%. Subdivided by clinical tumour size the chances are 0.96% in case of cT1 tumour and 7.0% in case of a cT2 tumour. For pathological T-status the numbers are respectively 0.87% en 5.0%. For pT1-2 this is 2.2%.
Conclusion: The risk of more than 2 positive axillary nodes is relatively small in patients with cT1-2 breast cancer. Ultrasonography of the axilla helps in further identifying patients with a minimal risk of additional axillary disease, putting ALND up for discussion.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-07.
Abstract P1-01-22: Which cytologically proven node-positive breast cancer patients can avoid axillary lymph dissection after neaodjuvant chemotherapy?
Authors: Karanlik H , Ilhan B , Fayda M , Yavuz E , Mudun A , Saip P , Eralp Y , Kurul S , Aydiner A 
Published: August 2014

Abstract
BACKGROUND:
It is still controversial whether axillary lymph node dissection can be omitted after negative sentinel lymph node biopsy in breast cancer patients with clinically positive axilla at presentation treated with neoadjuvant chemotherapy (NAC). The aim of this study was to analyze whether SLN biopsy could be useful in these patients.
METHODS:
After NAC of 112 patients with cytology-proven axillary node metastasis at the time of diagnosis, SLNB using radioisotope and blue dye was performed including completion node dissection between 2008 and 2012. The results of SLNB and clinicopathological characteristics were analyzed for correlation with pathological axillary lymph node status.
RESULTS:
SLN was successfully identified in 107 (95.5%) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Axillary status was predicted with 94% accuracy and a false negative rate of 8.7%. Axillary nodal status before NAC (cN2 versus cN12) was associated with higher false-negative rates (p = 0.02). Conversion to node-negative disease was achieved in 38 (35%) patients: 23% of patients with the luminal A subtype, 12% of patients with the luminal B, 39% of patients with the HER2-enriched, and 26% of patients with the triple-negative breast cancer subtype. The tripple negative and HER2-enriched breast cancer subtypes had a significantly better false negative rate and accuracy.
CONCLUSIONS:
SLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NAC. However, acceptable performance was noted for tripple negative and HER2-enriched breast cancer patients presented with N1 axillary status in the beginning of NAC, and thus SLNB might be safely considered in these selected patients.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-22.
Abstract P1-01-24: Preoperative ultrasound staging of the axilla superfluous peroperative examination of the sentinel node
Authors: Tjalma W , Van Berckelaer C , Van Goethem M , Verslegers I , Van Dam P 
Published: August 2014

Abstract
Background:
Axillary surgery in breast cancer is tailored. The current standard is to perform a frozen section or dep examination of the sentinel node during surgery. If the sentinel node is found positive (≥ macrometastases) a complete axilliary resection is recommended. Preoperative identification of positive nodes will lead to a further improvement of the tailored therapy.
Hypothesis:
A percentage of less than 5% of patients who would needed an additional operation is considered acceptable.
Material and Method:
From 2010 – 2012 all breast cancer patients of the Multidisciplinary Breast Clinic Antwerpen had an ultrasound evaluation of the axilla as part of their staging.
Fine needle aspiration cytology was performed of suspicious lymph nodes. If this showed to be positive, sentinel node biopsy was bypassed. Patients with normal nodes or benign/non diagnostic biopsy had removal of the sentinel node(s) without peroperative pathological examinations.
Results:
A total of 275 breast patients had an ultrasound staging (table 1). The sensitivity, specificity, positive predictive value and negative predictive value was respectively 90%, 85%, 77% and 94%.
Table 1: Ultrasound stagingEchoLN +LN -N1 (n = 117)9027N0 (n = 158)10148
Ten of the 275 patients (3.6%) needed an axillary clearance as a second procedure.
Discussion
Preoperative detection of invaded lymph nodes has several advantages. First of all it will allow you to identify patients with positive nodes, who can participate in neoadjuvant trial. Secondly it will save operating time and avoid overloading of the system for direct examination and reduces tissue loss. This approach will reduce costs for the health system and anesthetic time for the patient, with an acceptable reoperation rate.
Conclusion
Preoperative evaluation ultrasound staging of the axillare lymph nodes will avoid peroperative examination of the sentinel node at an acceptable reoperation rate. It is better for the patient, the physicians and the health care system.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-24.
Abstract P1-01-25: Predictive factors of micrometastases in the sentinel node of patients affected by invasive early breast cancer
Authors: Livi L , Meattini I , Bertocci S , Zei G , Cecchini S , Francolini G , Scotti V , De Luca Cardillo C , Orzalesi L , Casella D , Simoncini R , Nori J , Bianchi S , Biti G 
Published: August 2014

Abstract
Aim: nodal metastatic involvement is the most important prognostic indicator in breast cancer. Sentinel node biopsy led to an increase in the detection of micrometastases. The aim of our analysis was to identify predictive factors of micrometastases and macrometastases of sentinel node.
Materials and Methods: between January 2000 and December 2006, 675 patients were treated with breast surgery and sentinel node evaluation at University of Florence (Florence, Italy). Estrogen receptor status, progesterone receptor status, and Ki-67 labeling index determined with the MIB1 monoclonal antibody were assessed. HER2 immunohistochemistry (IHC) expression was scored as follows: 0, no staining or faint membrane staining; 1+, faint membrane staining in &gt;10% of tumor cells, incomplete membrane staining; 2+, weak to moderate membrane staining in &gt;10% of tumor cells; and 3+, intense circumferential membrane staining in &gt;10% of tumor cells. HER2 scores of 0 and 1+ were considered negative. HER2 IHC 3+ and fluorescent in situ hybridization (FISH) – amplified tumors were considered positive. All IHC 2+ tumors and indeterminate tumors were tested for gene amplification by FISH. The sentinel node was examined by hematoxylin and eosin. The patients were divided into three groups based on AJCC TNM staging: sentinel node negative (n = 601); micrometastases if tumor deposit more than 0.2 mm but &lt;2 mm (n = 20), and macrometastases if tumor deposit more than 2 mm (n = 53).
Results: at the logistic regression with polytomous analyses (outcome micrometastases or macrometastases), age (p = 0.048), menopausal state (p = 0.013), breast quadrant (p = 0.005), lymph vascular invasion (p = 0.0001), post-surgical T stage (p = 0.0001), histotypes (p = 0.023), HER2 status (p = 0.02), Ki-67 proliferative index (p = 0.001) and nuclear grade (p = 0.024) were significantly correlated with sentinel node macrometastases. Sentinel node biopsy technique (cytological aspiration versus histological biopsy) was not associated with micrometastases (p = 0.89) or macrometastases (p = 0.48) occurrence. The only feature significantly associated with micrometastases in sentinel node was the lymph vascular invasion (p = 0.0001).
Conclusion: the presence of micrometastases remained fairly constant over time if compared to macrometastases. In our experience the only feature significantly associated with micrometastases in sentinel node is the lymph vascular invasion.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-25.
Abstract P1-04-10: Assessment of circulating tumor cells (CTC) by RT/PCR as a surrogate marker for PFS in metastatic breast cancer (MBC)
Authors: Saber MM , Bahnasy AA , El-Zawahry HM , Allahloubi NM , El-Moetii MA , Abd El Fatah RM , Aid S , Ghareeb M 
Published: August 2014

Abstract
Background: Despite significant improvements in the treatment of metastatic breast cancer (MBC), it remains an incurable disease. The presence of circulating tumor cells (CTC) predicts for progression free survival (PFS) in (MBC) patients. We hypothesized that the change in level of CTCs can be a good surrogate marker for PFS.
Methods: CTC level was determined by flow cytometry (FCM) in the blood of MBC female patients with measurable or non-measurable evaluable disease excluding CNS metastasis 1) before starting taxanes (Docetaxel or Paclitaxel) regimen, 2) after the first cycle, and 3) at assessment of the disease after 3-4 cycles. The breast origin was further confirmed through assessment of CK19, mammaglobin, prolactin inducible peptide (PIP), aldehyde dehydrogenase 1 (ALDH1) and human chorionic gonadotropin (hCG) in the separated CTCs by quantitative real time PCR (QRT-PCR). CTC level and level of these markers were correlated with the clinical features of the patients, response to treatment and PFS.
Results: Sixty-six female patients were enrolled between May 2010 and Jan. 2011. The median age was 48.9 years and duct carcinoma was the main pathologic subtype. After a median follow up period of 20 months, median PFS was 6 months. There was a very strong relation between the selection marker CK-19 and the breast cancer markers (p value = 0.0001). Patients with baseline CTC &lt; 4 had significantly higher median, 6 months and 1 year PFS when compared with those with CTC ≥ 4 (p value = 0.03) while CTC levels did not correlate with PFS in the 2nd & 3rd samples respectively (p value = 0.28). Also patients whose CTC level decreased after treatment had significantly prolonged median PFS compared to patients whose CTC level increased (10 versus 4 months, p = 0.007).
Conclusions: CTCs; measured by RT-PCR were strongly predictive of PFS in MBC. CTC also could be of a great potential value in early assessment of response to chemotherapy after the 1st cycle especially in non-measurable lesions.
Key Words: Circulating tumor cells, metastatic breast cancer, progression free survival and RT-PCR.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-04-10.
Abstract P1-05-05: Epithelial cell reprogramming assay reveals inter-individual heterogeneity in stem/basal and progenitor cell profile of the normal breast
Authors: Nakshatri H , Anjanappa M , Bhat-Nakshatri P 
Published: August 2014

Abstract
Objectives: The majority of our understanding of mammary epithelial cell hierarchy is from mouse models. In addition, due to limited replication potential, primary cells of either mouse or human origin have rarely been used for functional studies. In this study, we took advantage of the recently developed epithelial cell-reprogramming assay that utilizes irradiated fibroblasts and ROCK inhibitor to characterize breast epithelial cells from individuals with varying degree of breast cancer risk.
Methods: Primary breast tissues were collected at the time of surgery and cultured either immediately or at convenient time after freezing in liquid nitrogen with ROCK inhibitor. Flow cytometry sorting was employed to fractionate and propagate stem-like/basal (CD49f+/EpCAM-), luminal progenitor (CD49f+/EpCAM+), and mature (CD49f-/EpCAM+) cell enriched fractions. Similar fractionation/characterization was performed using CD133, CD10, CD271, EGFR and ALDEFLUOR.
Results: Inter-individual variability was observed in proportion of CD49f+/EpCAM+, CD49-/EpCAM+ and CD133+ cells. Epithelial cells from a patient considered high risk based on the history of hyperplasia as well as cells from BRCA1 and BRCA2 patients displayed unique CD49f and EpCAM staining pattern compared to cells isolated from adjoining “normal” tissue of two cancer patients. In addition, CD133+ population was higher in BRCA1 and BRCA2 mutant patients. Morphologically, cells isolated from BRCA1 patient displayed higher levels of cells with mesenchymal phenotype. Upon short-term culturing of cells under regular 2D culture without reprogramming conditions, cell surface marker profile remained unchanged suggesting that most of the cell surface marker profile is cell intrinsic. CD49f+/EpCAM-, CD49f+/EpCAMhigh, CD49f+/EpCAMmedium, CD49f-/EpCAM+, CD133+/EpCAM+, and CD10+/EpCAM+ cells were amicable for further propagation in culture. CD49f+/EpCAMmedium cells cultured for two weeks remained CD49f+/EpCAMmedium. Additional marker profiling including cancer stem cell markers is underway to further refine stem, progenitor, and mature cells.
Conclusion: Ability to propagate distinct subpopulation of normal cells from patients with different breast cancer risk would allow investigation of the impact of cell type origin of cancer on the course of the disease including response to therapy and the development of in vitro assay for breast cancer risk assessment.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-05-05.
Abstract P1-06-09: Engineered model matrix to mimic cancer stem cell microenvironment: Effect of integrin and heparin binding peptides
Authors: Jabbari E , Sarvestani SK 
Published: August 2014

Abstract
Introduction: It is critical to understand the mechanism of cancer stem cell (CSC) maintenance and its regulation by the microenvironment to prevent and treat cancer. Since cancer takes many years to grow, it is imperative to develop in vitro models to study the molecular basis of tumorigenesis and progression. In an effort to isolate and investigate the effect of individual physical, mechanical, and biological factors in the tumor microenvironment on the fate of cancer cells and maintenance of CSCs, we have developed novel inert synthetic hydroxy acid-chain-extended polyethylene glycol (PEGXA) hydrogels with defined physical, chemical, mechanical, and biological properties. The objective of this work was to investigate the effect of integrin-binding and heparin-binding peptides conjugated to a matrix with defined physiochemical properties and stiffness on tumorsphere formation and CSC maintenance.
Methods: Mouse 4T1, human MCF7, and human MDA-MB-231 breast cancer cells were encapsulated in PEGXA gels conjugated with integrin-binding and heparin-binding peptides. Peptides included laminin-derived IKVAV and YIGSR, collagen-IV derived TAGSCLRKFSTMY and GEFYFDLRLKGDKY, and fibronectin-derived WQPPRARI and RGD. Gels without peptide conjugation and those conjugated with laminin-derived CD44 binding RLVSYNGIGGLK peptide were used as positive (CSC forming) and negative controls, respectively. Tumorsphere size and density, and expression of CSC markers were determined with incubation time in tumor CSC culture medium. For in vivo, cell encapsulated gels were inoculated in syngeneic Balb/C mice and tumor formation was determined with time.
Results: All tumor cells types encapsulated in PEGXA gels without peptide formed tumorspheres and maintained CSCs. Gel stiffness had a bimodal effect on tumorsphere formation in the 1-50 kPa compressive modulus range. Tumor cells encapsulated in the gel with 5 kPa compressive modulus had the highest expression of CSC markers. Conjugation of CD44 binding peptide eliminated tumorsphere formation by encapsulated tumor cells. Interestingly, integrin-binding peptides (RGD, IKVAV and YIGSR) conjugated to the gel abolished tumorsphere formation by encapsulated cells whereas heparin-binding peptides (TAGSCLRKFSTMY, GEFYFDLRLKGDKY and WQPPRARI) improved rate of tumorsphere growth and the expression of CSC markers. It should be noted that peptides dissolved in the gel (not chemically attached to the gel) or gels conjugated with mutant peptides did not have a noticeable effect compared to the gels without peptide. Similar results were observed with the cell-encapsulated gels were implanted in Balb/C mice. The expression pattern of EMT markers suggested that enhanced EMT contributed to the increased tumorsphere formation in gels conjugated with heparin-binding peptides.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-06-09.
Abstract P1-06-11: Tumor-associated macrophages: CD206 expression and patient outcomes in locally advanced breast cancer
Authors: Reynolds JM , Hodges DB , Salam A , Shaw ET , Magoon V , Werlang-Perurena AM , Singh HB , Speights VO , Ruud CO , Bhat A 
Published: August 2014

Abstract
Introduction
The ability of a tumor to recur is related to the complex molecular biology of the tumor cells and the surrounding microenvironment. Tumor-associated macrophages (TAMs) account for up to 50% of the cell mass within a breast tumor, and the M2 macrophage phenotype has been reported to have pro-tumor activity. The mannose receptor, CD206, is a transmembrane receptor expressed predominantly in macrophages and shown in mouse studies to promote M2/TAM activity. This study evaluates CD206 expression in the tumor stroma with patient outcomes in locally advanced breast cancer.
Methods
The Scott & White tumor registry was queried for consecutive cases of women diagnosed with stage 3, HER-2 negative breast cancer between January 1999 and December 2006. To meet inclusion criteria, all biopsies must have been performed at S&W and patients must have had at least 5 years of follow up in our system documenting status of cancer (complete remission vs. metastatic recurrence). Archived formalin fixed and paraffin embedded tissue breast tissue from initial surgical biopsies was obtained from the Scott & White Pathology Department. Sections were cut at 4 microns thick and slides were stained for CD206. Two pathologists without knowledge of the patients’ clinical backgrounds reviewed each slide. The hot spot method was employed at 20x power to identify the 3 spots in tumor stroma that stained most heavily. The number of CD206+ cells in each of 3 hot spots was counted, and the mean number of CD206+ cells per hot spot reported by two independent pathologists was averaged for analysis.
Results
65 patients met inclusion criteria, of these 31 had a recurrence within 5 years of diagnosis. There was no correlation between likelihood of recurrence or overall survival and CD206 expression. In the 31 patients that had a recurrence, a high CD206 count of greater than or equal to 15 was associated with a shorter time to recurrence than a CD206 count of less than 15 (14.8 months vs. 22 months, respectively, p = 0.028). Mean age at diagnosis in the recurrence group was 59.6 vs. 60 years, and 15 (60%) vs. 2(33%) patients were ER positive in the low CD206 (&lt;15) vs. high CD206 ( = &gt;15) groups, respectively.
Conclusion
High expression of CD206 in the tumor stroma was associated with a shorter time to recurrence in patients with stage 3, HER-2 negative breast cancer; however, there were more ER negative tumors in the high CD 206 group. Our research supports in vitro data that high CD206 expression in macrophages may represent a more aggressive tumor phenotype. Future studies focusing on studying CD206 expression in HER-2 positive breast tumors along with histological stratification are needed to confirm this finding.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-06-11.