bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-02-01: Predictive value of TILs in evaluation of 18F-FDG-PET in breast cancer
Authors: Hirakata T , Takaaki F , Kurozumi S , Katayama C , Yajima R , Obayashi S , Nakazawa Y , Tokuda N , Yanai K , Honda C , Kuwano H 
Published: February 2018

Abstract
Background:
Several recent clinical studies have evaluated the prognostic and predictive importance of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC). 18F-Fluorodeoxyglucose positron-emission (FDG-PET) CT was found to be effective for monitoring cancer cell viability of tissues and tumors, and it is used to evaluate the glucose metabolic rates of such tissues because most neoplasms have high glycolytic rates. FDG-uptake is also influenced by many factors, including inflammatory cells. In the present study, we investigated the relationship in evaluation of FDG-PET and degrees of TILs.
Patients and Methods:
Invasive carcinoma tissues of 100 breast cancer patients were examined. All patients underwent surgery. None of the patients had received preoperative chemotherapy. The proportional grades of stromal (Str)-TILs in surgical specimens were determined as follows: low (0-10%), intermediate (20-40%) and high (50-90%) grade, using the criteria of the International Working Group for TILs 2014 in breast cancer, using an immunohistochemical (IHC) method. The evaluation of PET was determined as follows, using standardized uptake value max (SUV max): low (&lt;5) and high (&gt;5). Estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, and nuclear glade were also measured by IHC.
Results:
Among the 100 patients, range of age was 36 to 86 (mean 58) years. Twenty-seven patients were pre-menopausal, seventy-one were postmenopausal, and two were unknown. Invasive ductal carcinoma was diagnosed in 97 (97%) of the patients, invasive lobular carcinoma was diagnosed in 2 (2%), and others was 1 (1%).We divided the cases into three groups based on the degrees of TILs, low (57%), Intermediate (33%) and high (10%). We divided the cases into three based on the degrees SUV max, low (78%) and high (22%). High TILs group significantly showed higher SUV max than that of lower SUV max group (P=0.009). High TILs group had statistically higher rates of ER negative (P=0.001), PgR negative (P=0.002), HER2 positive (P=0.007), and nuclear grade 3 (P=0.013) than those of low TILs group.
Conclusion:
The proportional grades of stromal (Str)-TILs were associated with the degrees of SUV max in primary breast tumor in FDG-PET. High FDG uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. From our findings, the evaluation of TILs is to be useful for predicting a better prognosis or therapeutic effect in cases with high FDG-uptake which indicate higher risk of recurrent disease.
Citation Format: Hirakata T, Takaaki F, Kurozumi S, Katayama C, Yajima R, Obayashi S, Nakazawa Y, Tokuda N, Yanai K, Honda C, Kuwano H. Predictive value of TILs in evaluation of 18F-FDG-PET in 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 P5-02-01.
Abstract P5-03-06: Novel targets of breast cancer associated with inflammatory tumor microenvironment
Authors: Tiwari RK , Ben Rahoma G , Tuli N , Bednarczyk R , Maniyar RR , Chakraborty S , Singh S , Mittelman A , Geliebter J 
Published: February 2018

Abstract
Breast cancer affects one in eight women in the USA. Considerable progress in the identification of genetic lesions and their modulation has resulted in newer therapies making breast cancer a manageable disease. However, triple negative breast cancer is still difficult to treat and warrants a search for newer targets. To this end, we focused our attention towards the modulation of the breast cancer epithelium by other cell types such as the endothelial cells and the macrophages. The migratory macrophages and the estrogen sensitive migratory endothelial progenitor cells (EPCs) constitute the cellular milieu within the tumor microenvironment which continuously modulates breast cancer epithelium. We analyzed the interactions of the breast cancer cell lines (MCF-7 and MDA-MB-231) with the highly proliferative human umbilical cord derived CD133+/CD34+/VEGFR-2+ EPCs and M1 polarized macrophages (activated THP-1 cell line) in two separate in vitro studies. The readouts were cell proliferation, changes in epithelial to mesenchymal transition (EMT), and cellular differentiation. We observed morphological and cellular growth changes in the EPCs on treatment with conditioned medium (CM) generated from breast cancer cells, consistent with vasculogenesis and in vitro tubulogenesis. Both, MDA-MB-231 and MCF-7 CM, treatments resulted in enhanced EPCs proliferation and differentiation. However, the differentiation patterns were distinct, with MCF-7 CM increasing the number of cell clusters, whereas MDA-MB-231 CM increasing the number of adherent spindle shaped cells. The paracrine interaction was also assessed with M1 polarized macrophages. We observed decreased cell viability in MCF-7 and MDA-MB-231 cells following activated THP-1 CM and exosome treatments. Analysis of exosomes from activated THP-1 indicated an upregulation of 13 miRNAs compared to unactivated THP-1. The miRNA hsa-miR-146a-5p had the highest upregulation (44 fold increase). This specific miRNA has been observed in senescent cell and it inhibits cell proliferation, suggesting a possible mechanism for exosome-associated growth inhibition. The analysis of the paracrine interactive mediators between breast cancer cells, EPCs, and M1 polarized macrophages is likely to yield viable novel clinically translatable therapeutic targets.
Citation Format: Tiwari RK, Ben Rahoma G, Tuli N, Bednarczyk R, Maniyar RR, Chakraborty S, Singh S, Mittelman A, Geliebter J. Novel targets of breast cancer associated with inflammatory tumor microenvironment [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 P5-03-06.
Abstract P5-07-10: Circulating microRNAs as early predictors of relapse in operable breast cancer
Authors: Agelaki S , Papadaki C , Stratigos M , Spiliotaki M , Markakis G , Mastrostamatis G , Mavroudis D , Ioannis S 
Published: February 2018

Abstract
Background: Metastasis remains a major threat for patients (pts) with operable breast cancer (BC). Recurrence could arise from a state of tumour dormancy during which there is growth restriction of undetectable micrometastases. The expression of dormancy and metastasis related miRNAs was evaluated in the plasma of pts with operable BC obtained before adjuvant therapy in order to discover novel biomarkers for the prediction of relapse.
Methods: Plasma miR-21, miR-23b, miR-190, miR-200b and miR-200c expression was assessed by qRT-PCR in 133 pts with early BC (non-relapsed, n=84; relapsed, n=49). Expression was classified as high or low according to the median values and was associated with pts' clinicopathological characteristics and clinical outcome.
Results: No correlation was observed between the expression of miRNAs and the clinicopathological characteristics of pts. After a median f-up of 90.5 mo, median Disease Free Interval (DFI) was significantly lower in pts with high compared to low miR-21 [105 mo vs not reached (NR); p=0.001], miR-200c (105.2 mo vs NR; p=0.007), or both miR-21 and miR-200c expression (81.37 mo vs NR; p=0.001). miR-21-high was also associated with decreased median Overall Survival (OS; p=0.041). In multivariate analysis the number of infiltrated axillary lymph nodes (N3 vs N0-N2, HR: 2.86; p= 0.004) and miR-21 expression (high vs low, HR: 2.824; p=0.001) were independent negative prognostic factors for DFI, whereas negative hormone receptor status (HR: 3.062; p=0.024) and miR-21 high (HR: 3.545; p=0.029) independently predicted for worse OS. Moreover, miR-21 expression was higher in pts presenting early relapse (defined as relapse at ≤ 3 yrs) compared to those without relapse at 5 yrs (p=0.032). Furthermore, higher miR-21 (p=0.038), miR-23b (p=0.039), miR-200b (p=0.027) and miR-200c (p&lt;0.001) levels were observed in pts with late relapse (at ≥ 5 yrs) compared to those without relapse.
Conclusions: Differential expression levels of metastasis and/or dormancy related circulating miRNAs are encountered before adjuvant therapy in pts with operable BC presenting subsequent relapse compared to non-relapsed pts. In addition, circulating miRNAs could predict for early or late recurrence years before clinical detection of metastases. These results merit prospective validation in an independent pt cohort.
Citation Format: Agelaki S, Papadaki C, Stratigos M, Spiliotaki M, Markakis G, Mastrostamatis G, Mavroudis D, Ioannis S. Circulating microRNAs as early predictors of relapse in operable 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 P5-07-10.
Abstract P5-09-02: Tβ4 expression in cancer-associated endothelial cells enhances progression of invasive breast cancer
Authors: Cai J , Jiang W 
Published: February 2018

Abstract
Background: Invasive breast cancer is a highly aggressive primary breast tumour with poor prognosis. As tumour angiogenesis is exhibited by invasive breast cancer, anti-angiogenic therapy has been intensively evaluated over the past decade. However, clinical studies were disappointing. Thymosin β4 (Tβ4), a multi-functional peptide, is associated with induction of angiogenesis, but the role of Tβ4 in tumorigenesis of invasive breast cancer is unknown. We tested whether Tβ4 inhibition could be a new target involved in tumour development and tumour angiogenesis for treatment of invasive breast cancer.
Methods: We have adapted a 3D co-culture system to acquire invasive breast cancer cells-associated endothelial cells (ECs), which is followed by characterising the differential gene expressions by PCR-based subtraction analysis. We performed Western blot analysis on the protein samples obtained from ECs-stimulated by invasive breast cancer cells. Expression of Tβ4 in invasive breast cancer was assessed by qPCR in the breast tissues (tumour, n=119; background, n=55), and protein expression confirmed by immunohistochemical examination in an invasive breast cancer tissue microarray. Finally, mice breast cancer xenografts plus non-invasively photoacoustic microscopy were used to analyse the effect of Tβ4 knockdown on the tumorigenesis of invasive breast cancer.
Results: We found that invasive breast cancer cells could stimulate an increase in Tβ4 expression in microvascular ECs. High Tβ4 levels were strongly associated with high malignant invasive breast cancer and poor clinical outcome. In vivo study showed that siRNA targeting Tβ4 blocked growth of invasive breast cancer in mice. Photoacoustic imaging revealed that knockdown of Tβ4 elicited anti-breast cancer growth, in part, through disruption of tumour vasculature. Our results demonstrate that endothelial cell-derived Tβ4 enhances the progression of breast cancer by up-regulating tumour angiogenesis and it indicates that a high level of tumour stromal Tβ4 is an independent predictor of poor outcome.
Conclusions: Inhibiting endothelial Tβ4 could be a new therapeutic target in anti-angiogenic strategy for treatment of invasive breast cancer.
Citation Format: Cai J, Jiang W. Tβ4 expression in cancer-associated endothelial cells enhances progression of invasive 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 P5-09-02.
Abstract P5-14-05: α-tocopherol succinate enhances the anti-tumor activity of pterostilbene against human breast cancer cells in vivo and in vitro
Authors: Tam K-W , Lee C-H 
Published: February 2018

Abstract
Background: The cancer preventive activity of vitamin E (α-tocopherol, α-TP) has been suggested by many epidemiologic studies. Our previous study showed that Tocopherol-Associated Protein (TAP), a major tocopherol–binding protein, is preferentially detected in normal breast tissues than in tumor regions among 93 clinical breast cancer patients, which postulate its tumor suppressive role in breast cells. Pterostilbene (3,5-dimethoxi-49-hydroxystilbene, PS) is a natural dimethylated analogue of Resveratrol found in different plants. Previous studies have shown that PS has the ability to induce apoptosis in a range of cancer cell lines. The purpose of our study was to assess the effect of TAP and Pterostilbene in tumor suppression of breast cancer cell.
Methods: Cell growth, proliferation, and viability were determined using the MTT assay. TAP protein expression was ablated in MDA-MB-231 breast cancer cell with nine independent siRNA sequences. MDA-MB-231 cells were transfected with pcDNA5 plasmids expressing the firefly luciferase gene. TAP protein expressions for each plasmid transfection were measured by western-blot analysis. Synergic effects of tumor growth and metastasis inhibitions in MDA-MB-231 xenograft animal model by PS and α-tocopherol treatment were evaluated.
Results: TAP served as a key molecular in responding to α-tocopheryl succinate (α-TOS) induced cell cycle regulation. PS has demonstrated the synergic decrease on breast cancer cell growth effects by the combination of α-TOS exposure. In animal model, treatment of PS and high level vitamin E diet not only induced breast tumor growth inhibition, but also suppressed tumor cell invasion by measuring circulation tumor cells in mouse blood.
Conclusions: Upon the evidences showed in this study, we suggest taking vitamin E and PS as supplements may provide both breast tumor preventative and therapeutic benefits in clinic.
Citation Format: Tam K-W, Lee C-H. α-tocopherol succinate enhances the anti-tumor activity of pterostilbene against human breast cancer cells in vivo and in vitro [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 P5-14-05.
Abstract P5-14-06: Towards breast cancer prevention through reduced breast density: Suppressive effects of tamoxifen on normal breast epithelial cells
Authors: Rosendahl AH , Puig Blasco L , Borgquist S 
Published: February 2018

Abstract
Background: Breast density is positively associated with risk of breast cancer and the local microenvironment in the normal breast is known to significantly impact breast cancer initiation and further progression. The selective estrogen receptor modulator tamoxifen, with beneficial clinical effects on breast cancer recurrence, has also been shown to reduce mammographic density potentially explaining the primary preventive effects of tamoxifen. Still, important gaps persist regarding the cellular and molecular basis of how tamoxifen modifies breast density and subsequently breast cancer risk.
Purpose: To investigate the impact by tamoxifen on normal human breast epithelial cells (MCF-10A) with the additional ambition to mimic variations in breast density on the cellular level.
Experimental design: Effects of tamoxifen on MCF-10A cells at different cellular densities were evaluated in vitro. Flow cytometry and the sulforhodamine-B assay were used to assess cell cycle distribution and proliferation. Cell adhesion to extracellular matrix proteins was analyzed using hexosaminidase assay. Modulation of integrin receptor levels was determined by Western immunoblotting.
Results: Tamoxifen exposure resulted in impaired cell cycle progression of human breast epithelial cells with a dose-dependent G2/M-phase arrest and reduced cell proliferation. Irrespective of tamoxifen treatment, the percent cellular adhesion to fibronectin and collagen type I by MCF-10A cells was significantly greater in high-density models compared to low-density models. Following tamoxifen treatment the adhesion was reduced in all density models. Consistent with the tamoxifen-induced lower adhesion, the integrin α1 and β3 levels were reduced in a dose-dependent way.
Conclusion: These data support the hypothesis that tamoxifen affects the normal breast epithelium and its adhesion capacity, which may contribute to the clinically observed decrease in breast density and a potential reduced risk of breast tumor establishment.
Citation Format: Rosendahl AH, Puig Blasco L, Borgquist S. Towards breast cancer prevention through reduced breast density: Suppressive effects of tamoxifen on normal breast epithelial cells [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 P5-14-06.
Abstract P5-19-03: Factors that influence posttraumatic growth in patients with breast cancer: A longitudinal trial
Authors: Berndt U , Gottschlik Y , Leplow B , Thomssen C 
Published: February 2018

Abstract
Objectives:
The main focus of previous research into coping with breast cancer, have been mostly with regards to the negative impacts such as emotional stress, anxiety, depression or cognitive dysfunction. However, patients also report positive changes that have come about as a result of their struggle with cancer. This is referred to as posttraumatic growth (PTG). The aim of this study was to assess the presence of PTG in breast cancer patients at two measurements and to explore the association between personality traits (resilience, optimism, self-efficacy) and positive emotions on PTG.
Patients and Methods:
The study group comprised of 80 women (with a mean age of 53.6 years, SD=10.2) recently diagnosed with stage I to III breast cancer. They completed self-report measures of PTG, resilience, optimism, self-efficacy and positive emotions up to three weeks after diagnose (t1) and then following by an update six months later (t2). Sociodemographic characteristics, emotional distress, anxiety and depression were also recorded.
Results:
Planned comparison: Breast cancer patients showed an increase of PTG from t1 to t2 (p=.00035). Resilience, optimism, self-efficacy and positive emotions did not change in the total sample from t1 to t2. Emotional distress, anxiety and depression have significantly declined from t1 to t2 (anxiety p=.015, depression p=.029, emotional distress p=.000065). Moreover, we found a significant positive correlation between positive emotions to PTG (r=-.386, p=.0004) and optimism to PTG (r=.334, p=.002) at t2, respectively. Depression t2 correlated negatively to PTG at t2 (r=-.264 p=.018).
Explorative results: We also calculated the difference between PTG t2 and t1. We found 67.5% (n=54) of the patients with an increase of PTG and 32.5% (n=26) without or with negative change. In a subgroup analysis we noticed that patients without benefit of PTG showed a decline of resilience (p=.015), self-efficacy (p=.028) and positive emotions (p=.045) between t1 and t2. Furthermore, anxiety and depression did not improve from t1 to t2 in this group.
Conclusions: Positive emotions and optimism represent indicators of PTG in breast cancer patients. A decline of anxiety and depression is associated with a higher rate of PTG. Psycho-oncological strategies related to these factors may support PTG in breast cancer patients. Future studies are needed to search for effective interventions to support patients in PTG.
Citation Format: Berndt U, Gottschlik Y, Leplow B, Thomssen C. Factors that influence posttraumatic growth in patients with breast cancer: A longitudinal trial [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 P5-19-03.
Abstract P5-22-05: Evaluation of simplified lymphatic microsurgical preventing healing approach (SLYMPHA) for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection
Authors: Ozmen T , Lazaro M , Zhou Y , Vinyard A , Avisar E 
Published: February 2018

Abstract
Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure however requires microsurgical techniques. The aim of this study was to assess the efficiency of Simplified-LYMPHA (SLYMPHA) in preventing LE in a prospective cohort of patients.
Methods: All patients, undergoing ALND with or without SLYMPHA between January 2014 and December 2016 were included in the study. SLYMPHA is a slightly modified and simplified version of LYMPHA. It is performed by the operating surgeon performing the ALND. One or more lymphatic channels identified by reverse arm mapping are inserted using a sleeve technique into the cut end of a neighboring vein. During follow-up visits, tape-measuring limb circumference method was used to detect clinical LE. Demographic, clinical, surgical and pathologic factors were recorded. The incidence of clinical LE was compared between ALND with and without SLYMPHA. Univariate and multivariate analysis were used to assess the role of other factors in the appearance of clinical LE.
Results: 406 patients were included in the study. SLYMPHA procedure was attempted in 81 patients and was completed successfully in 90% of patients. Early complication rates were similar between patients who underwent SLYMPHA and who did not (4% vs. 4.13%; p = 0.948). Median follow-up time was 15±13.73 [1-32] months. Patients, who underwent SLYMPHA, had a significantly lower rate of clinical LE both in univariate and multivariate analysis (3% vs 19%; p = 0.001; OR 0.12 [0.03-0.5]). Excising &gt; 22 lymph nodes and a co-diagnosis of diabetes were also correlated with higher clinical LE rates on univariate analysis, but only excising &gt; 22 lymph nodes remained to be significant on multivariate analysis.
Conclusions: SLYMPHA is a safe and relatively simple method, which decreases incidence of clinical LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.
Citation Format: Ozmen T, Lazaro M, Zhou Y, Vinyard A, Avisar E. Evaluation of simplified lymphatic microsurgical preventing healing approach (SLYMPHA) for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection [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 P5-22-05.