bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferation-based prediction for overall survival in locally advanced HER2(+) breast cancer.
Authors: Pedregal Manuel , Rojo Federico , Carames Sanchez Cristina , Lobo Francisco , Izarzugaza Yann , Cristobal Ion , Zazo Sandra , Moreno Irene , Zenzola Victor , Correa Andrea , Martinez Imanol , Hernández Roberto , Garcia-Foncillas Jesus 
Published: September 2018

e12007 Background: Breast cancer prognosis is influenced by several factors including Ki67 expression which may have a predictive role in luminal breast cancer patients. The aim of this study was to assess the value of Ki67 in breast cancers with positive hormonal receptors and HER2 overexpressed and to evaluate its impact on survival. Methods: Seventy eight consecutive patients diagnosed with locally advanced HER2 positive breast cancer who were treated with adjuvant therapy based on HER2 treatment were selected for this study (2004-2014). The adjuvant chemotherapy schemes were 44% TCH, 16% FEC, 11% AC/T and 29% other therapies. The median of followup was 68 months. Tumor proliferation was assessed immunohistochemically by Ki67 expression and calculated as percentage of stained tumor cells from this cohort previous to adjuvant chemotherapy administration and the results obtained were correlated with disease status and outcome. Results: High proliferation defined as a percentage > 15 of tumor cells was observed in 69% of the breast cancer patients cases. High proliferation significantly predicted longer overall survival (OS) (Log rank 0,012). At 10 years of follow-up, 93% of the patients with KI67 high expression were alive versus 43% of patients without overexpression. Multivariate analysis confirmed the clinical significance of Ki67 predicting OS for luminal HER2 breast cancer patients (p 0,04 y HR 9,6). Conclusions: High proliferation identifies a setting of luminal-B HER2+ subtype breast cancer patients with a significantly longer overall survival.
Longterm blood cell counts after intraoperative radiotherapy with or without whole breast radiotherapy in breast cancer patients.
Authors: Sperk Elena , Wersal Cornelia , Weiss Christel , Keller Anke , Kipke Anette , Tuschy Benjamin , Suetterlin Marc , Wenz Frederik K. 
Published: September 2018

e12014 Background: After radiotherapy changes in blood cell counts (BCC) can be seen. Leukocytopenia may have a negative impact on the immune system, outcome and quality of life of breast cancer survivors. No reports on changes of the three blood cell lines (leukocytes=WBC, erythrocytes=RBC, thrombocytes=PLT) after IORT w/o whole breast radiotherapy (WBRT) in breast cancer patients have been reported. Methods: 256 patients had IORT during breast conserving surgery. In 198 patients WBRT (46-50Gy/2Gy) + IORT (20Gy) and in 58 patients IORT as accelerated partial breast irradiation=APBI (20Gy) was given. Preoperative BCC were used as baseline. In 214 patients BCC were available after 1-90 days, in 139 during the 1st year, in 86 in the 2nd, in 66 in the 3rd, in 51 in the 4th and in 34 in the 5th year of follow-up. Dunnett-tests were used to calculate adjusted p-values (p<0.05=significant). Results: After IORT/WBRT a decrease of WBC was seen during the 1st year. Afterwards no changes were seen. After IORT APBI no changes were seen during 5 years follow-up. RBC was decreased at all time points after IORT/WBRT, and through the 1st year after IORT APBI. PLT decreased during the 1st year and stayed low during 5 years after IORT/WBRT. No changes in PLT were seen after IORT APBI. Hemoglobin (HGB) decreased after 3 months, during the 1st and 5th year after IORT/WBRT. After IORT APBI, HGB decreased only during the 1st year and stayed stable during follow-up. Conclusions: Decreases of all blood cell lines were seen at least transiently after IORT/WBRT. PLT and RBC stayed decreased. After IORT APBI, HGB and RBC decreased only during the 1st year and WBC and PLT remained stable during the whole follow-up. [Table: see text]
Breast cancer in "young" women: Age cutoff and clinicopathologic features.
Authors: Nie Gang , Wang Haibo , Song Yuhua , Mao Yan , Cao Weihong , Hu Haiyan 
Published: September 2018

e12019 Background: Age of patients play a key role in outcome of breast cancer, and therefore influences choice of treatment. In most studies, "young" is defined as being below 40 or 35 years. However, there are conflicts concerning definition of younger and older patients. In this study, we aim to establish a more appropriate age cut-off between “younger” and “older” breast cancer patients. Methods: A total of 5984 female breast cancer patients recruited in the Breast Cancer Registry of the Affiliated Hospital of Qingdao University during 2008 to 2014 were enrolled. Patients were divided into 11 groups by every 5 years’ age difference. The clinical characteristics and overall survival (OS) were compared among these age groups. Results: Among the five groups under age 45 (n = 1771, 30.0%), larger proportion of patients underwent breast conservation surgery in the “30-34” group (p = .027), and more patients were found with family history in the “25-29” group than in other groups (p = .029). No significant difference was found in OS (p = .059), clinicopathological stage, lymph node status, ER/PR status, HER2 status, or Ki-67 status among those five groups. For patients above 45 (n = 4813, 70.0%), differences were found in OS (p = .001) and significant differences with clinicopathological features (lymph node status, ER/PR status, HER2 status and Ki-67 status) were shown between younger and the older age groups (p = .001) among the six groups, except for family history (p = .066). Conclusions: Clinicopathological characteristics and survival status are similar among breast cancer patients under 45 years and vitiate among older patients. Age 45 is an appropriate cut-off for clinical grouping of breast cancer patients by age .
The underlying mechanism contributing to P-gp over-expression and drug resistance in the MCF-7 breast cancer cells induced by adriamycin.
Authors: Wang Guangji , Aa Jiye , Ge Chun 
Published: September 2018

e12028 Background: Continuous exposure of breast cancer cells to adriamycin (ADR) induces the over-expression of P-glycoprotein (P-gp) and multiple drug resistance. However, the biochemical process and underlying mechanisms are not clear. Our previous study revealed that ADR increased reactive oxygen species (ROS) generation and reduced glutathione (GSH) biosynthesis, while N-acetylcysteine, the ROS scavenger, reversed the over-expressed P-gp induced by ADR. Methods: Based on MCF-7 breast cancer cells and the adriamycin-resistant MCF-7 subline (MCF-7R), we investigated the P-gp expression on mRNA, protein and function level by qPCR, western blotting, flow cytometry and laser scanning confocal and so on, under SLC7A11 down-regulation/over-expression, cystine depletion/supplement, increased ROS generation and combined factors. Results: The present study showed that ADR inhibited cystine influx (source material of GSH) and SLC7A11 transporter (in charge of cystine uptake) in MCF-7 cells. For the first time, we showed that a down-regulation/silence of SLC7A11, or cystine deprivation, or an enhanced exposure of ROS agents directly and significantly increased P-gp expression; yet, a combination of either an inhibited/silenced SLC7A11 or cystine deprivation and an increased ROS dramatically promoted the P-gp expression in MCF-7 cells. On the contrary, an over-expression of SLC7A11, or sufficiently supplementary cystine, or scavenger of ROS significantly depressed P-gp expression and activity. Moreover, the down-regulation of SLC7A11 and cystine deprivation induced an elevation of ROS and P-gp that could be reversed by N-acetylcysteine. It was suggested that ROS and SLC7A11/cystine were the two relevant factors responsible for the upregulated expression and function of P-gp. Conclusions: This study provided the direct evidences suggesting that ROS triggered over-expression of P-gp and demonstrated that the combination of either an inhibition of SLC7A11 or cystine influx and elevated ROS was the underlying mechanism contributing to P-gp over-expression induced by ADR. It was indicated that the SLC7A11 might be a potential target modulating ADR resistance.
Analysis of factors related to adjuvant chemotherapy decision in early breast cancer patients with intermediate recurrence score.
Authors: Qu Feilin , Wu Jiayi , Chen Xiaosong , Huang Ou , He Jianrong , Zhu Li , Chen Weiguo , Li Yafen , Shen Kunwei 
Published: September 2018

e12032 Background: The 21-gene Recurrence Score (RS) assay has been routinely used to guide systemic chemotherapy in patients (pts) with estrogen receptor positive, node-negative early breast cancer (EBC). However, there has been less clarity in recommendation of adjuvant chemotherapy (ACT) in pts with intermediate RS (IRS). According to the definitions of IRS in retrospective NSABP B14, B20 trials and prospective validation of TAILORx trial, we adopted the broaden cut-offs of 11-30 in our study. We sought to analyze the factors related to ACT decision in this subset of pts. Additionally, the role of Adjuvant!Online (AOL) was evaluated in ACT decision. Methods: A cohort of 564 pts with RS of 11-30 was retrospectively analyzed from January 2014 to October 2016 in Ruijin Hospital Shanghai Jiaotong University School of Medicine. The Oncotype DX RS, a RT-PCR 21-gene assay, was performed on RNA extracted from formalin-fixed paraffin-embedded tissue. The AOL was used to determine pts’ clinical risk. Predictive factors of chemotherapy usage in different clinical risk catogories were also assessed. Results: 267 (47.3%) pts received chemotherapy. Age, tumor grade, pathologic type, pT, pN, molecular subtype and RS were significantly correlated with ACT decision ( p <0.05). These factors were all independent predictors of ACT usage ( p<0.05) in mutivariable model. AOL was successfully measured in 504 (89.4%) pts, of whom 279 (49.5%) were at low clinical risk and 225 (39.9%) had high clinical risk. The distribution of RS correlated significantly with AOL clinical risk catogories. The predictive factors of ACT administration in high and low clinical risk subgroups were highly consistent with the overall population, except pT in high clinical risk pts. Discordances between clinical risk and ACT decision were found in 158 pts (28.0%), probably due to different age, molecular subtype and RS. Conclusions: Age, tumor grade, pathologic type, pT, pN, molecular subtype and RS were independent predictors of ACT administration in EBC pts with IRS. AOL should not be used alone to aid chemotherapy decision in this subset of pts.
Clinical implications of genomic-directed therapies by comprehensive genomic profiling in breast cancer patients at a large academic cancer center.
Authors: Parrondo Ricardo Daniel , Mariotti Veronica , Gonzalez Velez Miguel , Leslie Lori Ann 
Published: September 2018

e12037 Background: Increased use of comprehensive genomic profiling (CGP) has recently led to improved genomic characterization of tumors, increased access to individualized therapies and increased availability of clinical trials in breast cancer patients. The aim of this study was to evaluate the clinical impact of genomic profiling in breast cancer patients with the use of a CGP assay at a large cancer center. Methods: We retrospectively analyzed 101 consecutive breast cancer patients who received CGP at the John Theurer Cancer Center between 12/2011 and 08/2016. Genomic alterations (GAs) were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA). GAs, number of available genomic-directed therapies and number of available clinical trials were reviewed. The CGP interrogated up to 315 genes and introns of 28 genes. Results: Median age at diagnosis was 58 years (range: 35-83 years). With a median follow-up of 189 months (range 1-189), median survival was 163 months (range 142-184). A total of 560 GAs were found in our population, with a median of 5.0 GAs/sample (range 0-16), a median of 2.0 therapies/patient (range 0-11), and a median of 11.0 clinical trials/patient (range 0-36). The most frequent GAs found were TP53 (47.5%, n = 48), PIK3CA (34.7%, n = 35), MYC (22.8%, n = 23), CCND1 (19.8%, n = 20), FGF3 (16.8%, n = 17), FGF4 (15.8%, n = 16), and ZNF703 (14.9%, n = 15). A significant positive correlation was found between number of GAs and the number of available targeted therapies and clinical trials (r = 0.5 and r = 0.7, p = 0.00, respectively). Increasing age is a predictor of having a PIK3CA mutation (OR = 1.05; CI:1.01-1.09, p = 0.00) while decreasing age is a predictor of having a MYC mutation by logistic regression (OR = 0.95; CI:0.91-0.95, p = 0.03). Conclusions: The systematic use of CGP led to the identification of a high number of GAs, which correlated with a median of 2.0 individualized therapies and a median of 11.0 clinical trials available for breast cancer patients. The clinical impact of genomic-directed individualized therapies needs to be further investigated in prospective, randomized studies.
First prospective multicenter Italian study on the impact of the 21-Gene Recurrence Score (RS) in adjuvant clinical decisions for ER+/HER2- early breast cancer (BC) patients.
Authors: Dieci Maria Vittoria , Guarneri Valentina , Giarratano Tommaso , Mion Marta , Tortora Giampaolo , Morandi Paolo , Gori Stefania , Merlini Laura , Oliani Cristina , Pasini Felice , Bonciarelli Giorgio , Griguolo Gaia , Orvieto Enrico , Del Bianco Paola , De Salvo Gian Luca , Conte Pier Franco 
Published: September 2018

e12038 Background: The Breast-DX Italy prospective study evaluated the impact of the 21-gene RS on adjuvant treatment decisions for early BC patients. Methods: The study was conducted in 9 centers of the Veneto Region (2 hub and 7 spoke). All consecutive patients with ER+/HER2-, T1 to T3, N0 to N1 early BC who met protocol-defined clinicopathological criteria for “intermediate risk” were included. Pre-RS and post-RS physicians’ treatment recommendations and treatment actually received were collected. Results: From November 2014 to August 2016, n=124 N0 and n=126 N1 patients were enrolled (65% at hub and 35% at spoke centers). The majority had PgR+ (86%), G2 (71%) and pT1c (63%) BC. Median age was 55 yrs, median Ki67 was 20% (range 2-70%). The distribution of RS was: <18 (61%), 18-30 (32%) and >30 (7%). Main factors associated with higher RS were G3 and higher ki67. The addition of chemotherapy (CT) to hormonal therapy (HT) was initially recommended for 48% of the patients (38% of N0 and 57% of N1 patients; 54% and 37% of patients enrolled at hub and spoke centers, respectively). The post-RS recommendation changed from the pre-RS recommendation for 40 patients, mostly from CT+HT to HT (n=30; n=25 with low and n=5 with intermediate RS). Change was more frequent for N1 patients (Table). Of the 72 N1 patients initially recommended to CT+HT, 28% had a post-RS indication to HT alone. The crude number of patients with pre-RS recommendation to CT significantly exceeded the number of patients who finally received it (absolute difference =31; p<0.001). The majority of CT treatments were spared at hub vs spoke centers (n=24 and n=7, respectively). Conclusions: Pre-RS indication to HT alone was frequent, in particular for N0 patients and at spoke centers. The use of the 21-gene RS further contributed in sparing CT administration, more so for N1 patients and at hub centers. The impact of the RS when used at discretion of the clinicians is currently under investigation in the prospective ROXANE study. [Table: see text]
Relationship of pathological features and a 21 gene expression assay in young women with early breast cancer.
Authors: Mutonga Martin Boniface Gitobu , Speedy Sedona , Uthe Regina , Kindy Kelly , Brownlee Aisha , Jain Sarika , Gradishar William John , Flaum Lisa E. , Santa-Maria Cesar Augusto 
Published: September 2018

e12050 Background: There is emerging evidence that a 21 gene expression assay recurrence score (RS) is prognostic independent of age. In practice, pathological markers may influence decision to recommend adjuvant chemotherapy. Methods: The primary objective of this study is to investigate the relationship between the RS and pathological markers between younger (29-49) and older (50-79) women with early stage ER+ breast cancer. Pathological markers investigated included the progesterone receptor (PR), grade, Ki-67, and P53. Patients who underwent 21 gene assay testing between 2002 through 2012 were sequantially identified. Data was extracted via the institutional tumor registry or chart reviewing. For each pathological feature, mean RS was compared between younger and older patients by t-tests. Trends in chemotherapy recommendation were assessed between younger and older patients within each RS risk category (≤10, 11-25, ≥26). Results: Between 2002 and 2012, 344 eligible patients were identified. 133 were ≤49 years of age, and 211 ≥50. There was no difference in distribution of RS across age (R2=3x10-4). Between younger and older patients, there was no difference in mean RS for any pathological marker (table 1). Within each age group, mean RS was always higher in tumors that were PR negative, grade 2/3, Ki67 >10%, and P53 ≥10% (p<0.05, respectively). In patients with a RS ≤10, 0% were recommended adjuvant chemotherapy irrespective of age. In patients with a RS 11-25, 39% of younger and 40% of older women were recommended chemotherapy. In patients with a RS ≥26, 100% of younger and 98% of older women were recommended chemotherapy. Conclusions: The relationships between pathological features and RS are consistent across age, supporting observations that the RS can predict benefit irrespective of age. See table. [Table: see text]
Association between weight gain during adjuvant chemotherapy (CTx) for early-stage breast cancer (BC) and survival outcomes.
Authors: Gutierrez-Barrera Angelica M. , Schvartsman Gustavo , Song Juhee , Ueno Naoto T. , Peterson Susan K. , Arun Banu 
Published: September 2018

e12057 Background: Obese and overweight women have an increased risk of BC and worse outcomes at the time of diagnosis compared to those at normal weight. Studies suggest that women tend to gain weight after BC cancer diagnosis and during CTx for early-stage disease, which may in turn increase risk for worse outcomes. We examined if weight gained during adjuvant CTx was associated with worse outcomes. Methods: We queried the prospectively maintained UT MD Anderson Cancer Center Breast Cancer (UTMDACC) Database for data on patients (pts) who received adjuvant third-generation CTx for early-stage BC cancer, including: demographics; tumor characteristics; and, body mass index (BMI) at diagnosis, pre- and post-CTx and one year after completion of treatment. Univariate and multivariate analysis (MA) by Cox regression were performed for survival outcomes across 3 categories according to BMI variation from start to end of CTx: >0.5-point loss or gain and stable BMI (± 0.5). Results: We included 1998 pts in this study. Women over 50 years old and post-menopausal were more likely to lose weight during adjuvant CTx, whereas women under 30 years old gained more weight (p<0.0001). At one year post-CTx, all pts tended to return to their original weight (ρ=0.3, p<0.0001). On MA, a BMI increase of 0.5 points was o associated with increased loco regional recurrence risk for both the entire cohort (HR 2.4; 95% CI, 1.122-5.166; p=0.0241) adjusting for grade and stage and for post-menopausal women (HR 3.774, 95% CI 1.241-11.447, p=0.0193) adjusting for Her2 status. Age <30 years old (HR, 2.52; 95% CI, 1.009-6.293; p=0.0478) and tumor stage 3 comparing to 1 (HR, 4.598; 95% CI, 2.754-7.677; p<0.0001) were associated with increased risk of death and tumor grade 2 (vs 3; HR, 0.547; 95% CI, 0.353-0.847; p=0.0069) was a protective factor on MA for the entire cohort. Conclusions: Weight gain during adjuvant CTx was associated with increased loco regional recurrence for the entire cohort and post-menopausal women, including pts who at year 1 returned to their normal weight. The effect of increased BMI during CTx on breast stroma, molecular profile and how it affects local recurrence is intriguing and needs to be further evaluated.
Neoadjuvant treatment of HER2 positive breast cancer with concomitant nonpegylated liposomal doxorubicin (NPLD), docetaxel and dual blockade with trastuzumab and pertuzumab: A retrospective analysis of pCR and cardiac safety.
Authors: Egle Daniel , Brunner Christine , Czech Theresa , Jaeger Thomas , Lang Alois , Hager Christopher , Poisl Clemens , Volgger Birgit , Marth Christian 
Published: September 2018

e12061 Background: Neoadjuvant treatment in HER2 overexpressing early breast cancer (EBC) has increased considerably. The Neosphere study, in which dual blockade of HER2 was combined with docetaxel resulted in favorable pCR rates. The addition of anthracyclines could play an important role in enhancing the effectiveness. The use of NPLD might be valuable in combination with HER2 targeted therapies. Safety and efficacy of NPLD, taxotere and trastuzumab was reported in the ABSCG 32 study. There is only little data about the cardiac safety and efficacy in combination with dual HER2 blockade. We report pCR-rate and cardiac safety of a single arm, retrospective, multicenter analysis of neoadj. treatment for HER2+ EBC. Methods: In this study 98 women with HER2+ EBC were investigated in 4 oncological departments in Austria. All patients were treated with NPLD (50 mg/m²), docetaxel (75 mg/m²) concurrent with trastuzumab and pertuzumab in standard dosage for 6 cycles as neoadjuvant therapy. All patients were free of cardiovascular disease and had a left ventricular ejection fraction (LVEF) of ≥50%. Cardiac function was measured by LVEF. All patients underwent surgery after neoadjuvant chemotherapy. The absence of any residual invasive cancer in the breast and axilla was defined as pathological complete response (pCR). Median follow up was 1.7 years. Results: Median age was 49 years. pCR rate was 73%. In this cohort a negative estrogen-and progesteron receptor was predictive for pCR (p<0.001). These patients achieved pCR in 89%. No patient progressed during treatment. Only one patient(1%) suffered symptomatic heart failure after surgery. Conclusions: We observed a considerably high rate of pCR in HER2-positive EBC treated with a combination of NPLD, docetaxel, trastuzumab and pertuzumab. Hormone receptor negativity was highly predictive for pCR. The addition of NPLD entails a very favorable cardiotoxicity profile. This regimen is a safe and highly effective treatment option in patients with HER-2 positive EBC.