bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transglutaminase II expression in invasive ductal carcinomas.
Authors: Assi Jasmeet Sunny , Srivastava Gunjan , Matta Ajay , Chang Martin , Ralhan Ranju , Walfish Paul G. 
Published: February 2017

34 Background: Molecular markers for predicting breast cancer patients at high risk of recurrence are urgently needed for more effective disease management. The impact of alterations in extracellular matrix components on tumor aggressiveness is under intense investigation. Overexpression of Transglutaminase 2 (TG2), a multifunctional enzyme, in cancer cells impacts epithelial mesenchymal transition and cancer stem cell phenotype, growth, invasion and interactions with tumor microenvironment. The objective of our study is to determine the clinical relevance of stromal TG2 overexpression and explore its potential to identify which IDCs are at high risk of recurrence. Methods: This retrospective study is based on immunohistochemical analysis of TG2 expression in 168 invasive ductal carcinomas with clinical, pathological and follow-up data available for up to 12 years. TG2 expression was correlated with clinical and pathological parameters as well as disease free survival (DFS) of breast cancer patients. Results: Stromal TG2 overexpression was observed in 97/168 (57.7%) invasive ductal carcinomas (IDC). Notably, IDC patients showing stromal TG2 accumulation had significantly reduced disease free survival (mean DFS = 110 months) in comparison with patients showing low expression (mean DFS = 130 months), as revealed by Kaplan-Meier survival analysis (p <0.001). In Cox multivariate regression analysis, TG2 accumulation in tumor stroma emerged as an independent risk factor for recurrence in IDC (p = 0.006, Hazard’s ratio, H.R. = 3.79). Conclusions: Accumulation of TG2 in tumor stroma is an independent risk factor for identifying breast cancer patients at high risk of recurrence. TG2 overexpression in tumor stroma may serve as a predictor of poor prognosis for IDC of the breast.
Women's understanding of personal breast cancer risk: Does ethnicity matter?
Authors: Herman Jonathan D. , Herman Sarah M. 
Published: February 2017

4 Background: A woman’s understanding of her breast cancer risk is an important precursor for care. A valid estimate allows for greater opportunity to consider early detection modalities and chemopreventive medications. The USPSTF recently encouraged women who have an increased risk of developing a first breast cancer and a low risk of side effects to take tamoxifen or raloxifen. The objective of this study is to compare patients' perceived breast cancer risk with their calculated risk and then parse those findings by ethnicity. Methods: Anonymous, IRB approved, pre-piloted questionnaires were filled out by women at 21 mammography centers on Long Island. The survey included questions about patient demographics, patient’s estimates of their own breast cancer risk and personal risk factors. Results: 9,873 respondents qualified for inclusion in our analysis. Women were asked to quantify their breast cancer risk by age 90. Overall, 707 (9.4%) were in line with their risks, 3,359 (44.7%) underestimated risk and 3,454 (45.9%) overestimated their risk. When parsed by ethnicity, of the 781 African Americans, 8.7% were in line, 57.6% underestimated risk, and 33.7% overestimated risk. Of the 245 Asians, 10.2% were in line, 58.8% underestimated risk, and 31% overestimated risk. Of the 427 Hispanics, 8.9% were in line, 50.4% underestimated risk, and 40.8% overestimated risk. Of the 6850 Caucasians, only 10.2% were in line, 38.6% underestimated risk, and 51.3% overestimated risk. Conclusions: Most women lack accurate knowledge of their own breast cancer risk – 90.6% overall. When parsed by ethnicity, while there was a statistical difference between groups, the difference was not important because overall understanding was very low. Caucasian women tended to overestimate their risk compared with other ethnic groups, possibly resulting in unnecessary anxiety. African American and Hispanics tended to underestimate risk compared with Caucasians, possibly resulting in underutilization of available resources. Patients must have a better understanding of their personal risk. Study findings should help refocus educational efforts because increased knowledge of breast cancer risk will enable providers to tailor an individual’s medical treatment plan.
Can Oncotype DX Recurrence Score (RS) be used in Luminal A and Luminal B breast cancer patients (pts) to predict the likely benefit of chemotherapy? A retrospective unicentric study in Spanish population.
Authors: Estevez Laura G. , Calvo Isabel , Fernandez-Abad Maria , Cruz Juan Jose , Suarez Ana , Lopez-Rios Fernando , Hidalgo Manuel 
Published: February 2017

40 Background: The 2011 St Gallen guidelines recommend the use of Ki67 as a surrogate marker for luminal A and Luminal B breast cancer subtypes. Pts with luminal B subtypes should be treated with adjuvant chemotherapy. The guidelines also recognize the Oncotype DX RS as a predictor of chemotherapy benefit. The aim of this study is to assess the distribution of the RS in luminal A and luminal B breast cancer subtypes as defined by Ki67. Methods: Data from 131 pts with invasive breast cancer for which Oncotype DX results and pathology data were available. Pathological assessment was evaluated by the same pathologist. Estrogen (ER) and progesterone (PR) receptor was assessed by immunostaining (cut-off 10% nuclear staining). Ki67 was assessed by IHC [high (≥14%) and low (< 14%)]. Histological grade was performed by using Nottingham grading system. Results: Median age: 50 (range: 35-78); premenopausal status: 53 pts (44.2%). Median tumor size: 1, 5 cm (0, 3-5); Median of Ki 67 index: 15 (range: 3-63); 79 pts (66.4%) had negative-lymph nodes. Seventy (58.3%) tumors were classified as Luminal B (Ki 67 ≥14%) and 50 (41.7%) as Luminal A. Grade III were more common in Luminal B 14 (20.3%) than in Luminal A 1 pts (2%) patients (p=0.003). Chemotherapy was the first recommendation in 29 pts (41.4%) with Luminal B vs. 7 pts (14%) with Luminal A; hormonotherapy was the first recommendation in 32 pts (45.7%) with Luminal B and 37 pts (74%) in Luminal A (p =0.003). In the Luminal B group, Recurrence Score results was low in 42 (60%) pts, intermediate in 19 (27.1%) and high in 9 (12.9%) while in the Luminal A group 31 (62%) had low; 16 (32%) intermediate and 3 (6%) high Recurrence Score results (p=0.433). RS changed the first treatment recommendation in 35 (50%) cases of Luminal B subtype vs. 14 (28%) cases in Luminal A subtype (p=0.016). Conclusions: The results show that a substantial number (60%) pts with Luminal B breast cancer subtype had a low RS, therefore preserving them from adjuvant chemotherapy treatment. The wide range of RS in both Luminal B and Luminal A breast cancer subtypes confirm the important role of Oncotype DX in treatment decision making.
Clinicopathologic characteristics and survival outcomes in multifocal and multicentric breast cancer.
Authors: Fushimi Atsushi , Yoshida Atsushi , Takahashi Osamu , Hayashi Naoki , Yagata Hiroshi , Suzuki Koyu , Tsunoda Hiroko , Yamauchi Hideko 
Published: February 2017

41 Background: Although multifocal and multicentric (MF/MC) breast cancers are a common entity, their clinical behaviors are not well characterized. We evaluated the impact of MF/MC on the disease-free survival (DFS) and distant disease free survival (DDFS) of breast cancer patients and compared clinicopathological characteristics between MF/MC breast cancers and breast cancers with single lesion. Methods: We retrospectively analyzed 734 consecutive patients who had invasive breast carcinoma and underwent definitive surgery at the St Luke’s International Hospital from January 2004 to December 2006. MF or MC ware defined as more than one lesion in the same quadrant or in separate quadrants, respectively. DDFS and DFS ware calculated by The Kaplan–Meier method. Univariate analysis was performed using the log rank test and multivariate analysis by Cox proportional hazards models. Results: Of 734 patients, 136 (18.5%) had MF/MC disease. MF/MC disease was associated with smaller tumor size (P <0.001). Multivariate analysis shows that MF/MC disease did not have an independent impact on DDFS or DFS adjusting by age, ER status, tumor size, lymphovascular invasion, lymph node metastases and nuclear grade. Conclusions: MF/MC breast cancers were not associated with poor prognostic factors, and were not independent predictors of worse survival outcomes. Our findings support the current TNM staging system of using the diameter of the largest lesion to assign T stage.
High levels of proliferation regulators and an impaired senescence response pathway to identify early-stage breast tumors with a poor prognosis.
Authors: Lanigan Fiona T. , Dunne Eiseart J. , Brien Gerard L. , Al Oraifi Fatima , Fan Yue , Quinn Cecily , Flanagan Louise , Fridberg Marie , Jirstrom Karin , Geraghty James G. , Gallagher William M. , Bracken Adrian P. 
Published: February 2017

43 Background: Predicting the risk of tumour recurrence, and thus the need for chemotherapy, for lymph node-negative breast cancer patients is a significant problem for clinicians and patients. Methods: We have identified a ‘core proliferation signature,’ which is consistently high in proliferating primary cultures, and is downregulated during cellular senescence. Using a reverse engineering approach on a breast cancer-specific regulatory network, and confirmed by ChIP-seq analysis, we have identified a hierarchy of several highly interconnected Master Transcriptional Regulators upstream of these core proliferation genes. Results: Further analysis of the expression of these factors in breast cancer cohorts at the mRNA and protein levels reveals a remarkable ability to reliably predict recurrence risk for early-stage breast cancer. Strikingly, in our analyses, a combination of just two of these factors outperforms the currently used clinical biomarkers for breast cancer recurrence risk, as well as recently developed multi-gene prognostic assays. Moreover, the addition of the senescence regulator p16INK4A to this panel further increases its prognostic capability. Conclusions: We propose that this novel approach has succeeded in identifying ‘drivers’ of breast cancer proliferation which, when combined with a marker of senescence such as p16INK4A, successfully identify actively proliferating tumours with an impaired senescence response pathway. Furthermore, we suggest that this gene combination has the potential to become an improved prognostic assay for early-stage breast cancer.
A prospective study on behavioral symptoms’ impact to the quality of life in patients with early-stage cancer receiving radiotherapy.
Authors: Xiao Canhua , Felger Jennifer , Mister Donna , Liu Tian , Miller Andrew H. , Torres Mylin Ann 
Published: February 2017

46 Background: Fatigue, sleep problems, and depression are the most common behavioral symptoms experienced by breast cancer patients. The purpose of this study was to examine these behavioral symptoms’ impact on quality of life (QOL) for early stage breast cancer patients receiving radiotherapy (RT). Methods: This was a prospective study of 46 patients receiving whole breast RT (50 Gy plus a 10 Gy boost) following lumpectomy. Data were collected at pre-RT, week 6 of RT, and 6-weeks post-RT. QOL was measured by Short Form-36, fatigue by Multidimensional Fatigue Inventory, sleep by Pittsburgh Sleep Quality Index, depression by Inventory for Depressive Symptomatology-Self-Rated, and stress by Perceived Stress Scale. No patients were treated with chemotherapy. Demographic/clinical variables, including age, race, marriage, smoking history, hormone treatment, and cancer stage, were collected at the time of enrollment. Mixed effect modeling was utilized to observe behavioral symptoms’ impact on QOL over time. Results: Fatigue and depression, along with stress, had significant impact on QOL after controlling for body mass index (BMI; the only one significant demographic/clinical variable; see Table). Patients with more fatigue, depression, or stress were more likely to have worse QOL during and post-RT. Patients having a higher BMI at baseline also reported worse QOL over time. Sleep was significantly correlated with QOL in univariate analyses, while this effect disappeared in multivariate models. Conclusions: Behavioral symptoms, in particular fatigue and depression, along with stress, have significant impact on the QOL of early breast cancer patients’ receiving RT. Future research on the underlying biological mechanisms will improve our understanding of these symptoms and their relationships, which will help to find potential targets for multiple related symptoms and, ultimately, improve patients’ QOL. [Table: see text]
The prospective estimation of blood serum free IGF-1, insulin concentration, and body mass index as a prognostic factor for breast cancer patients.
Authors: Nowara Elzbieta , Huszno Joanna , Drosik-Rutowicz Katarzyna , Nowara Ewa , Maslyk Barbara 
Published: February 2017

47 Background: Numerous epidemiologic findings suggest that an increase in IGF-1, insulin concentration and body mass index correlates with the risk of developing certain types of malignant tumors, including breast cancer. They may also have an influence on the cancer stage. The purpose of this study was to prospectively evaluate the correlation of body mass index (BMI), insulin, and free IGF-1 concentration with cancer stage. Methods: Prospective analysis has been conducted in 2011 in Cancer Center and Institute of Oncology in Gliwice, Poland. This study has been approved by Bioethics Committee according to national regulations. The pilot group included 138 patients with breast cancer treated with chemotherapy, 76% in adjuvant setting and 24% due to cancer dissemination. Results: Patients’ median weight was 70kg (range 52-106kg) and median BMI was 27 (range 18.8-40.8). Patients with HER2 overexpression had diabetes more frequently (8% vs. 0%), p=0.06. Patients with higher BMI more frequently had negative steroid receptor status (42% vs. 25%) p=0.06, and significantly more often were in postmenopausal period (81% vs. 52%), p=0.00029. Tumor stage was significantly more advanced in patients with lower physical activity, p=0.04. Tumor stage was insignificantly more advanced in patients with higher plasma insulin level, p=0.09. Multivariate analysis had shown that overweight patients with more advanced stage of breast cancer had negative steroid receptors more often, p=0.033. Patients with metastatic breast cancer often had higher insulin plasma levels in comparison to patients with early breast cancer (7% vs. 1%), p=0.09. The multivariate analysis also showed that patients with diabetes had more frequently more often overexpression of HER2 and were in a more advanced cancer stage, p=0.03. Conclusions: Hyperinsulinemia may be a risk factor for more advanced stage of disease. There is a possibility that the effect of being overweight on breast cancer stage is mediated by estrogen metabolism. This analysis is scheduled to be performed later in the project.
Receptor status change from primary to residual breast cancer after neoadjuvant chemotherapy (NCT) and analysis of survival outcome.
Authors: Parinyanitikul Napa , Lei Xiudong , Chavez-Mac Gregor Mariana , Mittendorf Elizabeth Ann , Litton Jennifer Keating , Woodward Wendy A. , Zhang Hong , Hortobagyi Gabriel N. , Gonzalez-Angulo Ana M. 
Published: February 2017

48 Background: Treatment and prognosis of breast cancer is determined by tumor subtype. Tumor heterogeneity and lack of stability in ER, PR and HER2 has been described. We evaluated the changes receptor status between primary and residual disease after NCT and its association with outcome. Methods: 398 women with known ER, PR and HER2 status in primary and residual disease were identified. Patients were classified as no receptor change vs. any receptor change. For ER and PR we explored absolute percent changes. Descriptive statistics were used. Kaplan-Meier method was used to estimate overall (OS) and recurrence-free (RFS) survival. Cox proportional models were fit to determine the association of receptor status changes with outcomes after adjustment for patient and disease characteristics. Results: From the 398 patients, 162 (40.7%) had a change in at least one biomarker. Twenty-three (10.9%) of the 211 ER-positive tumors changed to ER-negative and 39 (20.8%) of the 187 ER-negative tumors changed to ER-positive. Fifty-seven (35.2%) of the 162 PR-positive tumors changed to PR-negative and 28 (11.9%) of the 235 PR-negative tumors changed to PR-positive. Lastly, 29 (40%) of the 72 HER2-positive tumors changed to HER2-negative and among the 35 trastuzumab-treated patients, 16 (45.7%) had HER2 status changed. At a median follow up of 40 months, 128 women (32%) had died, and 167 (41.8%) had experienced a recurrence. Five-year OS estimates were 73% and 63% for patients with or without any receptor change, (P=0.07); 5-year RFS estimates were 63% and 48% for patients with or without any receptor change, (P=0.003). Among patients with baseline ER-positive tumors, 5-year OS estimates was 73% and 87% (P=0.03), and the 5-year RFS estimates was 59% and 71% (P=0.03) for those whose absolute ER percent decrease was less than 20% or more than 20%, respectively. A change in any receptor was associated with better RFS (HR: 0.63, 95% CI 0.44-0.9) but not with OS, (HR: 0.79, 95% CI 0.53-1.18). Conclusions: Changes in ER, PR and HER2 status between the primary and the residual disease after neoadjuvant chemotherapy are frequent. In this study, a change in biomarker status was associated with significant improved RFS.
Outcomes of sentinel lymph node-positive breast cancer patients treated with mastectomy without axillary therapy.
Authors: FitzSullivan Elizabeth , Kuerer Henry Mark , Bassett Roland L. , Mittendorf Elizabeth Ann , Yi Min , Hunt Kelly , Babiera Gildy , Caudle Abigail Suzanne , Black Dalliah M. , Bedrosian Isabelle , Meric-Bernstam Funda , Hwang Rosa F. 
Published: February 2017

53 Background: Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have a low rate of regional recurrence when treated with breast conserving surgery and radiation. Patients who fit criteria for the ACOSOG Z0011 trial are candidates to avoid completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment, including CLND and/or radiation therapy (XRT). Methods: We utilized an institutional database to identify patients who were treated with a TM for invasive breast cancer and had a positive SLN from 1994-2010. CLND was defined as removal of 10 or more lymph nodes. Clinicopathologic factors were analyzed and the rate of regional recurrence as well as overall and disease-free survival were determined. Results: A total of 730 patients with invasive breast cancer and a positive SLN were treated with TM including 71 patients who did not have CLND or XRT and 27 patients who did not have CLND but did receive XRT. Median follow-up was 66 months. The 10-year actuarial rate of regional recurrence was not significantly different for patients who received no further axillary treatment when compared to those who underwent CLND and XRT (4.9% vs 3.1%) or to those who underwent CLND without XRT (4.9% vs 1.4%). Survival was not significantly different between patients who did not receive further axillary treatment compared to those who underwent CLND without XRT or those who underwent both CLND and XRT. Using a nomogram previously developed by our group, the predicted probability of additional non-SLN involvement was significantly lower for patients who did not undergo CLND compared to those who did (10% vs. 23%, p<0.0001). Conclusions: In select patients with early stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.
Utilization of accelerated partial-breast irradiation (APBI) and guideline concordance: Analysis of the National Cancer Database.
Authors: Shaitelman Simona Flora , Lin Heather , Shen Yu , Bedrosian Isabelle , Bloom Elizabeth S. , Babiera Gildy 
Published: February 2017

54 Background: ASTRO published a consensus statement on patient suitability for APBI treatment to guide physician practice. The purpose of this study was to examine utilization trends of APBI in the American College of Surgeons’ National Cancer Database and to assess changes in APBI use following publication of the ASTRO guidelines in 2009. Methods: A total of 337,910 women were identified who were diagnosed from 2004 to 2010 with non-metastatic invasive breast cancer or ductal carcinoma in situ who were treated with breast conserving surgery and radiation therapy (RT) to the breast. Patients were divided by the type of treatment received (whole breast irradiation (WBI) or APBI) and by suitability to receive APBI as defined by the ASTRO Consensus Statement. Logistic regression was applied to study APBI use overall and within consensus statement categorization. All p-values are two-sided. Results: For all patients, APBI usage increased as an alternative to WBI over time, from 3.8% in 2004 to 10.8% in 2008, with a subsequent decline to 9.9% in 2010, due to a decline in APBI use for “cautionary”/“unsuitable” patients (p<0.0001). Overall rates of APBI utilization were higher among “suitable” than “cautionary”/“unsuitable” patients (range 6.9% to 16.9% vs. 3.1% to 7.8%, p<0.0001). Among all patients, the most common modality of delivering APBI was brachytherapy (82%), followed by external beam RT (17%) and intraoperative RT (1.0%). For both “suitable” and “cautionary”/“unsuitable” patients, factors associated with treatment with APBI included treatment after 2004 (p<0.0001), well differentiated histology (p<.0001), and smaller tumor size (p<0.0001). For “cautionary”/“unsuitable” patients, those with grossly negative tumor margins were more likely to receive APBI, as were “suitable” patients treated at an academic or comprehensive community cancer program compared to a community cancer program (both p<0.0001). Conclusions: The highest absolute rate of use of APBI was seen in the group considered “suitable” by ASTRO guidelines. Although significant increases have also been seen among less suitable cohorts, these rates have declined since the publication of the ASTRO guidelines in 2009.