bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of cardioprotective medications on breast cancer survival: A retrospective study from an academic center from Southern Illinois.
Authors: Regmi Manjari Rani , Parajuli Priyanka , Cheema Asad , Lara Garcia Odalys Estefania , Tandan Nitin , Maini Ruby , Sahib Hamsa , Mirihagalle Noupama , Koester Cameron , Niaz Zurain , Abedrabo Sabree , Johnson Alexander , Ibrahim Abdisamad M. , Bhandari Bishal , Delfino Kristin , Robinson Kathy , Desai Meghna R. , Kulkarni Abhishek 
Published: May 2020

e12540 Background: Cardiovascular disease is one of the leading causes of deaths in breast cancer patients. Pre-existing cardiac conditions and cardiovascular risks associated with chemotherapy affect the overall mortality of these patients. Cardio protective medications like beta-blocker, ACEIs, ARBs, statin, and potassium-sparing diuretics have shown to increase the survival odds. In our study, we investigated the survival of breast cancer patients who were on cardio protective medications. Methods: Our retrospective cohort study included breast cancer patients from Simmons Cancer Institute, Springfield, Illinois from January 1st, 2014 to December 31st, 2017. The first step comprised of screening patients using ICD code of breast cancer. Next, a retrospective chart review led to selecting eligible patients with biopsy proven breast cancer diagnosis within the aforementioned dates. We excluded patients who were diagnosed outside the give time frame. Data on age, gender, medical comorbidities, medications, and survival status were also collected. Comparisons between categorical variables were compared with the Chi-Squared test. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival are assessed with Cox proportional hazards regression analyses. Results: Screening using ICD codes resulted in 1618 patients. Of those, 478 had biopsy proven diagnosis within the dates mentioned. 301 out of 478 patients were on some kind of cardio protective medication (88 on beta-blockers, 73 on ACEIs, 41 on ARBs, 87 on statins, and 12 on potassium sparing diuretics). We looked into survival analysis in patients on different cardioprotective medications. ARBs and potassium sparing diuretics showed increased likelihood of survival as the hazard ratio (HR) was found to be 0.512 (95% Cl: 0.068-3.832, p-value:0.0919) and HR 0.390 (95% CI: 0.130-1.66, p-value:0.514) respectively. In contrast, other cardio protective medications showed decreased trends for survival. The HR of beta blocker was 1.734 (95% CI: 0.508-5.919, p-value: 0.379) and of ACEIs was 1.350 (95% CI: 0.395-4.613, p-value: 0.632). Similarly, statins had a hazard ratio of 1.534 (95% CI: 0.512- 4.594, p-value:0. 444). Conclusions: We found that the cardio protective medications showed no statistically significant difference in survival in breast cancer patients. Given the smaller sample size and single center study, further multi-center clinical trial is warranted to establish a stronger association.
Radiation therapy following breast conserving surgery (BCS) in women with early-stage breast cancer and low oncotype scores.
Authors: Damico Nicholas , Kharouta Michael , Lyons Janice A. , Harris Eleanor Elizabeth 
Published: May 2020

e12547 Background: Clinical trials have demonstrated radiation therapy (RT) significantly reduces local recurrence following BCS, but that omission of RT does not compromise survival in the majority of women with early stage, low risk breast cancer. Criteria for omission of RT have been based on clinical factors such as age, stage, tumor size, surgical margins and estrogen receptor (ER) status. The utility of Oncotype DX RS in determining benefit of RT is not well defined. Methods: The National Cancer Database (NCDB) was queried for women ages 50-69 with T1N0M0, grade 1-2, ER+, Her2- breast cancer who underwent BCS with negative margins and had Oncotype DX RS of 0-18. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between patients who received RT and endocrine therapy (ET) versus ET alone using logrank analysis. Propensity matching was performed to reduce the impact of potential confounders and balance sample bias. Cox proportional hazards regression was used to identify predictors of OS. Results: A total of 13,648 women met inclusion criteria. The median age was 60 years. 13,389 women had adjuvant RT+ET, while 259 women had ET alone. Five year OS was 98.6% in patients who underwent RT+ET compared to 95.5% in those that had ET alone (p = 0.0012). Propensity-matching by age, Charlson Deyo Comorbid Condition score, tumor size, Oncotype RS, and race. Five year OS in the propensity matched cohort was 99.6% for women receiving RT+ET, and 98.3% for ET alone, which was not significantly different (p = 0.095). On multivariate analysis receipt of radiotherapy was not predictive of survival. Age and comorbidity score were the only significant predictors of survival. Conclusions: Patients who receive adjuvant RT with low risk, early stage ER+/Her2- breast cancer had higher OS than women who received ET alone on univariate analysis. However, results from both multivariate analysis and propensity score matching suggest no survival benefit to the addition of RT. Prospective studies are underway assessing omission of RT on the basis of multigene assays rather than clinical features alone. [Table: see text]
Prognostic value of circulating nucleosomes in primary breast cancer.
Authors: Mego Michal , Kalavska Katarina , Karaba Marian , Minarik Gabriel , Benca Juraj , Sedlackova Tatiana , Manasova Denisa , Pindak Daniel , Mardiak Jozef , Celec Peter 
Published: May 2020

e12553 Background: Nucleosomes are composed of DNA wound around histone proteins and represent the basic structural unit of chromatin in the nucleus. When cells die, nucleosomes get out of the cell and end eventually in the circulation. Plasma nucleosomes might serve as a non-specific biomarker of cell death, which might be of particular interest for non-invasive tumor monitoring. The aim of this study was to assess the prognostic value of circulating nucleosomes in primary breast cancer. Methods: This study included 92 primary breast cancer patients treated with surgery from March 2012 to February 2015, for whom plasma isolated on the day before surgery was available in the biobank. Plasma nucleosomes were detected using Cell Death Detection ELISA kit with anti-histone and anti-DNA antibodies. Results: Circulating nucleosomes were associated with the systemic inflammatory index (0.17 vs. 0.27, P = 0.02) and with aldehyde-dehydrogenase expression (0.22 vs. 0.15, P = 0.03). Patients with lower than mean nucleosomes had significantly better disease-free survival (HR = 0.46, P = 0.05). The prognostic value was most pronounced in lymph node positive disease with high proliferation rate and in patients with detectable circulating tumor cells with epithelial-to-mesenchymal transition, but negative for epithelial circulating tumor cells. In a multivariate analysis, nucleosomes, hormone receptor status, HER2 status, lymph node involvement and tumor grade were independent predictors of disease-free survival. Conclusions: Our data suggest prognostic value of plasma nucleosomes in primary breast cancer and their association with metastatic ability and stem-cell ness characteristics. Their quantification could be added to the established prognostic markers.
Immunological changes with perception of cold in breast cancer (BC) patients.
Authors: Gandhi Shipra , Sarma Maithreyi , Attwood Kristopher , Ambrosone Christine B. , Repasky Elizabeth A. , Hong Chi-Chen 
Published: May 2020

e12559 Background: Tumor-bearing mice “feel colder” than non-tumor bearing mice and prefer to be at thermoneutral temperatures. Cold stress results in immunosuppressive tumor microenvironment [decrease in CD8+T-cells, increase in myeloid derived suppressor cells and T-regulatory cells]. Cytokines play a significant role in modulating these immune cells. Breast cancer (BC) patients frequently report feeling excessively cold under ambient temperature. We examined the association between cytokine levels and thermal discomfort symptoms in BC patients in the Women’s Health After Breast Cancer (ABC) Study treated at Roswell Park Comprehensive Cancer Center. Methods: 424 stage I-III BC patients were identified. Standard demographics, body mass index (BMI), race, grade, histological subtype, tumor size, stage, nodal status, treatment received, and menopausal status were recorded. Peripheral blood was prospectively collected at diagnosis and one year post diagnosis and analyzed for a panel of 27 cytokines. Patients completed a questionnaire reporting symptom of “feeling cold when others are fine” using a Likert scale one year post BC diagnosis. Relationships between cytokines levels as tertiles and symptoms of “feeling cold” were evaluated using logistic regression. Change in cytokine levels from the time of BC diagnosis to one year post were also evaluated [ > 20% decrease, no change (-20 to +20%), and > 20% increase]. Results: Overall, 195/424 (46%) patients reported “feeling cold”. There were no differences in patient and tumor characteristics between patients who reported “feeling cold” vs “not cold.” Interestingly, 53.4% patients on chemotherapy reported “feeling cold” (p < 0.05). At baseline, higher IL-17E and IL-6 were associated with decreased perception of feeling cold (p < 0.05, p < 0.01). At one year post diagnosis, higher TNF-β was associated with decreased perception of feeling cold (p < 0.05). Changes in IL-22 and IL-33 were associated with increased perception of feeling cold (p < 0.05, p < 0.05). Multivariate model adjusted for age, race, BMI, histological subtype, stage, grade, treatment and menopausal status showed a trend towards decreased cold perception with higher IL-6 but was not statistically significant. Conclusions: We observe significant differences in pro-tumorigenic IL-6 and anti-tumorigenic IL-17E & TNF-β cytokines in BC patients reporting thermal discomfort. This suggests avenues for using thermal therapies to modulate inflammatory cytokine production in breast cancer.
Prognostic value of tumor: Infiltrating lymphocytes and androgen receptors correlation in triple negative breast cancer.
Authors: Tecic Vuger Ana , Separovic Robert , Vazdar Ljubica , Pavlovic Mirjana , Sitic Sanda , Tecic Vuger Ana , Sarcevic Bozena , Vrbanec Damir 
Published: May 2020

e12571 Background: Little is known about correlation of tumor infiltrating lymphocytes (TIL) and androgen receptors (AR) and their joint effect on early triple-negative breast cancer (TNBC) prognosis. Analyzes to date evaluated mostly stromal TIL (sTIL) and intratumoral (iTIL), but not separately in central tumor (CT) and invasive margin (IM). Methods: We retrospectively analyzed consecutive sample of 152 early TNBC patients treated at our institution 2009-2012. TIL and AR were assessed using standard FFPE samples, TIL according to International Working Group for Evaluation of TIL recommendation, sTIL and iTIL in CT and IM, and AR by immunohistochemistry. Results: Median age was 58, 84% NOS, median T 2.2cm, 41% N+, 22%, 59% and 19% in stage I, II and III, respectively. Radical mastectomy was performed in 39%, adjuvant chemotherapy in 88% and radiotherapy in 74% of patients. Positive AR defined as ≥1% nuclear-stained cells, were expressed in 31%, and AR≥10% in 26% of patients. Median TIL content was: sTIL 19%, iTIL 5%, TIL in CT 5%, at IM 18%, sTIL in CT (CTs) 5%, iTIL in CT (CTi) 1%, sTIL at IM (IMs) 30%, and iTIL at IM (IMi) 5%. Prevalence of intermediate or high TIL content, defined as ≥10% was: CTs in 48%, CTi in 23%, IMs in 86%, and IMi in 47% of cases. In bivariable analysis all TIL indicators were significantly associated with longer OS, while AR was not. After adjustment for potential confounders using Cox proportional hazard regression, significant predictors of OS were sTIL (p0.007), IM TIL (p0.002), IMs (p0.001), and IMi (p0.030). In all cases higher TIL content was associated with longer OS. Although AR was not significant predictor of OS, it's interactions with TIL IMs and IMi was. There was no significant difference in OS between patients with high IMs and low IMs and AR0, but those with high IMs and AR≥1 had HR0.22 (p0.045) for death compared to patients with low IMs and AR0. Also, no difference for high IMi and low IMi and AR0, but patients with high IMi and AR≥1 had HR0.10 (p0.028) for death compared to patients with low IMi and AR0. Conclusions: Section analysis reveals frequent intermediate to high density and statistically significant prognostic impact of TIL on IM. That directs question towards role of different tumor compartments. Furthermore, combination of high expression of IMs and IMi with AR≥1 appears to be associated with longer OS than in patients with high IMs and IMi but with AR0. The correlations between AR and all TIL studied are extremely small, indicating their independence, but if so, their interaction in impact on OS is particularly interesting.
4D radiomic biomarker of functional tumor heterogeneity to predict breast cancer recurrence in pretreatment dynamic FDG-PET.
Authors: Chitalia Rhea , Viswanath Varsha , Pantel Austin R. , Peterson Lanell , Cohen Eric , Muzi Mark , Karp Joel , Mankoff David A. , Kontos Despina 
Published: May 2020

e12573 Background: Breast cancer heterogeneity is thought to be associated with adverse outcomes. Dynamic molecular imaging modalities, including PET, permit 4-D sampling of tumor biologic properties and can therefore capture functional heterogeneity revealed by the temporal dimension of the dynamic tracer uptake. With the goal of improved non-invasive characterization of in vivo tumor biology, we have developed and tested a novel radiomic biomarker that characterizes 4-D functional tumor heterogeneity (FTH). We hypothesize subclonal populations are spatially contiguous regions of shared physiologic behavior that drive breast cancer heterogeneity and can be quantified. We describe an initial application of this approach to FDG PET imaging of breast cancer. Methods: We retrospectively analyzed data from a study of 50 patients with locally advanced breast cancer. Patients underwent 60-minute dynamic FDG PET over the chest prior to neoadjuvant chemotherapy and breast surgery and were followed for disease recurrence (DFS). A 3-D region bounding each tumor was identified by a radiologist and a novel Markov Random Field based 4-D segmentation paradigm segmented each tumor into three spatially constrained sub-regions with distinct time activity curve dynamics. From each tumor, an FTH imaging signature was extracted characterizing cluster compactness and separation. FTH imaging signatures were z-score normalized across all patients. Time-to-event analysis was used to assess the prognostic value of the FTH imaging signatures in predicting DFS. Discriminatory capacity compared to a baseline model of established prognostic factors (age, hormone receptor status, baseline tumor size) and standard PET uptake and kinetics markers (SUV, K1, and Ki) shown to be predictive of DFS (Dunnwald, J Clin Oncol 26:4449, 2008) was evaluated using the c-statistic and the log-likelihood statistical test. Results: 17 of 50 women (34%) had recurrence events. Adding FTH imaging signatures to the baseline model of age, baseline tumor size, and hormone receptor status improved a cross validated c-statistic from 0.51 to 0.74 (p < 0.05), and demonstrated higher discriminatory capacity over a model of age, tumor size, hormone receptor status, and standard PET measures (c-statistic = 0.59). Conclusions: Imaging biomarkers of 4-D metabolic tumor heterogeneity may add prognostic value in predicting recurrence-free survival in breast cancer and merit further study.
Axillary management after neoadjuvant chemotherapy in breast cancer: A survey by Brazilian Society of Mastology.
Authors: Frasson Antonio Luiz , Lichtenfels Martina , Resende Heloisa Magda , Barbosa Fernanda , Miranda Isabela , Borba Alessandra , Falcone ANA Beatriz 
Published: May 2020

e12609 Background: Several trials have been investigating the accuracy of sentinel lymph node biopsy (SLNB) in clinically node-positive breast cancer patients undergoing neoadjuvant chemotherapy (NAC). A survey of breast surgeons was performed to assess the current management of axilla after NAC in Brazilian clinical practice. Methods: Brazilian Society of Breast Surgeons members were invited by email to complete an anonymous online survey. From 2000 eligible members, 426 (21.3%) members responded the survey. Results were summarized as proportions based on the number of responses to each question. Results: The majority of responders, 43.4%, indicated performing routine axillary staging by physician exam, ultrasound and PAAF (if necessary) in patients who are to undergo neoadjuvant chemotherapy. Approximately 43% of responders perform SLNB instead of ALND in patients with N1 axillary involvement before neoadjuvant chemotherapy, however many breast surgeons also indicated SLNB for N2 (27.7%) and N3 (18.8%) patients. Axillary complete pathologic response (ypN0) is necessary to omit ALND for 42.8% of responders and 19.5% do not perform ALND in patients getting ypN1is+ (isolated tumoral cells). Considering the option with patients getting ypN1is+ (isolated tumoral cells) and ypN1mic (micrometastases), 24.5% reported not performing ALND after SLND. Fifty-eight participants, 13.8%, accepted only SLNB in patients getting ypN1is+ (isolated tumoral cells), ypN1mic (micrometastases) and ypN1. The molecular profiling of breast tumor is considered when choosing axillary management after neoadjuvant chemotherapy for 26.3% of responders and for 73.7% the molecular profiling is not influencing the decision. Conclusions: Our survey highlighted the trend toward de-escalation of axillary surgery in patients undergoing neoadjuvant treatment and a high heterogeneity in axillary management after chemotherapy in Brazilian practice.
Giant tumors of the breast in adolescents and types of reconstruction during thelarche.
Authors: Kern Peter 
Published: May 2020

e12614 Background: Tumors like cystosarcoma phylloides may exhibit malignant potential and occur already in young adolescents in their thelarche. Adolescents often do not report the growth of a tumor in the breast due to lack of knowledge or shame. The necessity for surgical intervention interferes with the normal development of the breast, however must be performed due to the deformation of the growing breast and the malignant potential of cystosarcoma phylloides. Methods: We report on two young girls, 13 years of age, who presented with giant cystosarcoma phylloides and fibroadenomas, with tumor diameters of 9 and 13 cm in their thelarche with extension to whole volume of the breast. Results: Both tumors were removed via an axillary access to the breast to avoid scars in the developing breast and removed with free margins at first surgical intervention. Autologous reconstruction by lateral thoracic wall advancement mammaplasty in one patient and implant based reconstruction as a temporary spacer have been used for reconstruction. The young patients showed a high degree of satisfaction in validated Breast QoL questionnaires. Conclusions: Surgical intervention in giant cystosarcoma phyllodes of the breast in adolescents require careful planning of surgery and avoid unnecessary scars in the developing breast. Axillary approach for surgical removal of the tumor and replacement by thoracic wall advancement mammoplasty or temporary implant-based reconstruction may both be safely applied in thelarche.
Gene expression profiling involved in response to neoadjuvant therapy in breast cancer.
Authors: Bofill Salvador , Garrigos Carmen , Benavent Marta , Gonzalez Rosario , Montaño Alvaro , Falcon Gonzalez Alejandro 
Published: May 2020

e12618 Background: Neoadjuvant systemic therapy for breast cancer is used increasingly but, there is a group of patients which do not benefit from this therapy. With these premises, we stablished that our main objective was to identify differential expression genes patterns in patients (pts) with the ER/PR- Her2+, ER/PR+ Her2+ and triple negative (TN) subtypes breast cancers according to response to neoadjuvant therapy. Methods: RNA from formalin fixed paraffin embedded tumor samples from 54 pts with breast cancer that had received neoadjuvant therapy was extracted with mirVana miRNA isolation kit (Ambion). Patients with TN subtype received neoadjuvant chemotherapy based on anthracyclines and taxanes and patients with the Her2+ subtype received treatment with taxanos-trastuzumab and anthracyclines. The RNA expression levels were identified by ClariomD Asssay (ThermoFisher). Results were analyzed with Transcriptome Analysis Console and with in-house scripts in R (version 3.5.1). Data were corrected and normalized using Robust Multichip Average method from the oligo package. Expression was summarized at gene level using the corresponding annotation for ClariomD array BrainArray. Expression analyses were performed with limma package. A fold change ≥ 2 and p < 0.05 was considered statistically significant. We defined to groups: R (response, RCB 0) and NR (not response, RCB III) pts. Results: The median age of the pts was 52 years and 58% were menopausal and 42% pre-menopausal. Tumor stage were T1 9%, T2 50%, T3 30%, T4 11% and lymph node involvement were N0 31%, N1 41%, N2 24%, N3 4%. We obtained twelve genes differentially expressed in R vs NR groups. Respect to TN, two genes (AC053503.12, C9orf153) were differentially expressed between R (n = 11) and NR (n = 11). In ER/PR+ Her2+ subgroup, NBPF4 showed a differential expression in R (n = 8) vs NR (n = 7). In pts with ER/PR- Her2+, nine genes (DHRS2, SLCO1B3, UGT2B15, RGS2, SULT1E1, MED23, FKBP5, MIEN1, HER2) were differentially expressed in R (n = 10) vs NR (n = 7). We have started a validation in an independent cohort of pts in ER/PR+ Her2+ subgroup, confirming the results previously obtained. Conclusions: We found twelve genes differentially expressed in the different molecular subtypes of breast cancer involved in the response to neoadjuvant therapy. Several of these genes, especially UGT2B15, SULT1E1, FKBP5, MIEN1 and HER2 have been reported as key genes in tumoral processes, such as cell proliferation, invasion and drug resistant pathways, suggesting that its could be good biomarkers of response to neoadjuvant therapy in breast cancer.