bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-05-07: Molecular profiles of screen detected breast cancers: Final results of Turkish Bahcesehir breast cancer screening project
Authors: Cabioglu N , Ozkan-Gurdal S , Kayhan A , Ozaydin N , Ozcinar B , Aribal E , Ozmen V 
Published: August 2014

Abstract
Objectives: Turkish Bahcesehir Breast Cancer Screening Project is a 10-year organized population based screening program carried out in one of the largest counties of Istanbul, Turkey. The aim of our study is to examine the biological features of screen detected breast cancers detected during the initial 4-year study period as an interim analysis.
Study Design and Methods: Between January 2009 and May 2013, a total of 6298 women with ages 40–69 years were recruited in this prospective study. Two-view mammographies were obtained by 2-year intervals, and classified according to Breast Imaging Reporting and Data System of the American College of Radiology (ACR). Clinicopathological and biological tumor characteristics were analysed for those diagnosed with breast cancer. Tumors were stained for estrogen (ER) and progesterone receptors (PR), HER2-neu and Ki-67 by immunohistochemistry.
Results: A total of 57 breast cancers (%0.9) were detected during the study period. The median age was 50 (40-70). The majority of patients (72%) were stage 0 or 1, whereas 28 patients (49%) were &lt;50 age. Of 57 tumors, 45 (79%) were invasive cancers and 12 (21%) were ductal carcinoma in situ. Forty-eight patients (86%) underwent breast conservation, whereas 37 patients (65%) had sentinel lymph node biopsy only as axillary procedure. Of 45 invasive cancers, 31 (69%) were ductal carcinoma and 8 (18%) were pure lobular cacinoma. Among 45 invasive cancers stained for ER, PR, HER2-neu and Ki67, the majority of them (91%) were ER or PR receptor positive, whereas 11% were HER2-neu positive and 58% had low Ki67 levels (≤15). As molecular subtypes, the majority of them were found to be either luminal A (57%) or luminal B type (34%), whereas other nonluminal HER2 (4%) and triple negative cancers (5%) were less frequently detected.
Conclusions: Our findings suggest that the majority of screen-detected breast cancers exhibit either luminal A or B subtype. However, more aggressive subtypes such as nonluminal HER2-neu or triple negative cancer are less likely to be detected by mammographic screening programs, requiring other preventive strategies.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-05-07.
Abstract P4-06-05: Transcriptional heterogeneity correlates with chemotherapy sensitivity in triple negative breast cancer and varies by molecular subtype
Authors: Jiang T , Shi W , Ononye S , Han G , Wali V , Pusztai L , Hatzis C 
Published: August 2014

Abstract
Purpose: Different molecular subtypes of breast cancer are believed to have different degrees of molecular heterogeneity. However, the heterogeneity of breast cancer subtypes has not been formally compared. The goal of this analysis was to develop metrics of global transcriptional heterogeneity, compare heterogeneity across breast cancer subtypes and assess whether heterogeneity metrics correlate with sensitivity to chemotherapy in basal-like cancers.
Methods: Affymetrix U133A gene expression data from 836 breast cancers (basal n = 219, HER2-like n = 147, luminal A n = 343, luminal B n = 127) were analyzed. Among the basal-like cancers, 128 received neoadjuvant chemotherapy (pathologic complete response, pCR, n = 44; residual disease, RD, n = 94). Molecular class was assigned by the PAM50 classifier. We used the average pairwise Pearson distance, the sum of eigenvalues of the correlation matrix and multi-dimensional scaling dispersions of the probe set expression values to quantify heterogeneity. Distribution of each metric within the different subtypes was estimated from 500 bootstrapped cohorts of 80 cases in each subtype. We used analysis of variance (ANOVA) to evaluate the significance of the differences in heterogeneity between subtypes.
Results: All three heterogeneity metrics yielded concordant results. Within subtypes, heterogeneity was greatest in basal-like cancers followed by HER2-like, luminal B and luminal A (see figure). Luminal A cancers were distinctly less heterogeneous than the rest. Basal-like cancers with RD were more heterogeneous than those with pCR. The best metric to separate basal tumors with pCR versus RD was the sum of eigenvalues shown below.
Conclusion: Breast cancer molecular subtypes differ in transcriptional heterogeneity. Luminal A cancers have the lowest within group heterogeneity while basal like cancers have the highest. Among the basal-like cancers, those with high chemotherapy sensitivity (pCR) are more homogeneous than those with RD suggesting that transcriptional heterogeneity might be contributing to increased resistance to therapy in this subgroup.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-06-05.
Abstract P4-07-12: miR-206 inhibits cell migration through direct targeting of the actin-binding protein coronin 1C in triple-negative breast cancer
Authors: Wang J , Tsouko E , Jonsson P , Bergh J , Hartman J , Aydogdu E , Williams C 
Published: August 2014

Abstract
Patients with triple-negative breast cancer (TNBC) have an overall poor prognosis, which is primarily due to a high metastatic capacity of these tumors. Novel therapeutic approaches to target the signaling pathways that promote metastasis are desirable, in order to improve the outcome of TNBC patients. A loss of function of a microRNA, miR-206, is related to increased metastasis potential in breast cancers but the mechanism remains to be elucidated. In this study, we show that miR-206 was decreased in TNBC clinical tumor samples and cell lines whereas one of its predicted targets, actin-binding protein CORO1C, was increased. Expression of miR-206 significantly reduced proliferation by inducing a G1-S cell cycle arrest and migration and also repressed CORO1C mRNA and protein levels. We demonstrate that miR-206 interacts with the 3’-untranslated region (3’-UTR) of CORO1C and regulates this gene post-transcriptionally. Further, silencing of CORO1C reduced tumor cell migration and affected the actin skeleton and cell morphology, similar to miR-206 expression, but did not reduce proliferation. Our findings suggest that miR-206 targets CORO1C in TNBC cells, thereby affecting the actin filaments which results in a repressed tumor cell migration. This pathway is a novel mechanism offering a mechanistic basis whereby the metastatic potential of TNBC tumors could be targeted.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-12.
Abstract P4-09-04: Weight loss and lipid-lowering efficacy of a low carbohydrate, calorie restricted diet intervention on postmenopausal breast cancer patients
Authors: Krie AK , Bohlen KN , Demuth H , Ageton C , Norfolk D , Kittelsrud J , Thomes R , Fahrendorf A , Muth J , Rojas-Espaillat LA , Davies GE , Hu Y 
Published: August 2014

Abstract
Background: Obesity and weight gain are associated with higher rates of breast cancer recurrence and increased mortality. Cardiovascular disease is a leading cause of death in breast cancer survivors. Control of body weight and cardiovascular risk factors are key aspects in breast cancer survivorship. The purpose of our study was to see if a low carbohydrate, calorie restricted dietary intervention could be implemented in a group of obese postmenopausal breast cancer survivors to achieve weight loss and improved lipid profiles.
Methods: Twenty-four postmenopausal estrogen receptor positive breast cancer patients were enrolled on a low carbohydrate, calorie restricted dietary intervention. The dietary intervention utilizes 0.5g protein/pound (actual body weight), less than 40 grams of carbohydrates, and 800-1200 calories per day. Body weight, body fat percentage, blood triglyceride level, and total cholesterol level were measured and monitored, during the dietary intervention.
Results: The average weight loss spanned 23.8 weeks (varying from 5 to 59 weeks). When compared with the mean body weight prior to the dietary intervention, the mean body weight was reduced by 19.9% (equivalent to 43.7 pounds). The mean body fat percentage was reduced by 6.86%. In addition, the dietary intervention significantly decreased the patients’ blood triglyceride level by 33.8% (p = 0.00013). The mean total cholesterol level was decreased by 9.5% with the dietary intervention (p = 0.00498).
Conclusion: This study demonstrated that a low carbohydrate, calorie restricted diet resulted in significant weight loss with improved lipid profiles. This study suggests that this dietary intervention is feasible in postmenopausal breast cancer survivors and a potential strategy for cardiovascular risk reduction.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-09-04.
Abstract P4-12-18: BOLERO-3: Quality-of-life maintained in patients with metastatic breast cancer treated with everolimus plus trastuzumab plus vinorelbine
Authors: Isaacs C , Ozguroglu M , Jerusalem G , Xu B , Láng I , O'Regan R , White M , Fasolo A , Litton J , Toi M , Shen K , Andre F , Vuylsteke P , Zhang Y , Zhang J , Taran T , Wilks S 
Published: August 2014

Abstract
Background: Activation of the PI3K/mTOR pathway is implicated in resistance to trastuzumab. Accordingly, the BOLERO-3 study evaluated the efficacy of adding everolimus (EVE), an mTOR inhibitor, to vinorelbine and trastuzumab. At the final progression-free survival (PFS) analysis, EVE significantly improved PFS vs PBO (hazard ratio [HR] = 0.78; log-rank P = .0067) but EVE-treated patients had higher rate of grade 3/4 toxicity. To further qualify the benefit:risk of adding EVE to trastuzumab-based therapy, per-protocol, patient-reported, health-related quality-of-life (HRQoL) data were analyzed.
Methods: BOLERO-3 is a randomized phase 3, double-blind, placebo-controlled, international multicenter trial. Taxane-pretreated patients (N = 569) with trastuzumab-resistant, HER2+, advanced breast cancer were randomized (1:1) to treatment with EVE or placebo (PBO) plus vinorelbine and trastuzumab. The European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire C30 (QLQ-C30) (including the breast cancer-specific BR23 module) was administered at baseline and every 6 weeks thereafter until progression. The QLQ-C30 consists of 30 items combined into 15 subscales, including Global Health Status and functional subscales, where higher scores (range, 0 to 100) indicate better HRQoL. Time to definitive deterioration (TTD) based on a 10% decrease from baseline for GHS and for the physical, emotional, and social function subscales was determined using the Kaplan-Meier method. Treatment arms were compared using a 2-sided log-rank test stratified by prior use of lapatinib.
Results: Overall, there was no significant difference in median TDD of HRQoL between treatment arms. The median TTD in global health status score was 8.3 months for EVE (95% confidence interval [CI], 6.9-11.5) vs 7.3 months for PBO (95% CI, 5.6-10.4; P = .8386). The median TTD in the physical, emotional, and social function subscale scores showed no significant difference between arms. For example, median TTD in the physical function subscale score was 12.0 months (95% CI, 8.3-14.1) for EVE vs 12.5 months (95% CI, 8.3-20.9) for PBO (P = .4251), and median TTD in the emotional function subscale score was 15.2 months (95% CI, 9.2-17.3) for EVE vs 12.5 months (95% CI, 9.7-16.4) for PBO (P = .8140).
Conclusions: These analyses demonstrate that, despite increased frequency of adverse events observed with the addition of EVE to the standard treatment of vinorelbine and trastuzumab, overall and functional HRQoL scores were not negatively impacted in patients with trastuzumab-resistant, HER2+, advanced breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-18.
Abstract P4-12-19: BOLERO-3: Everolimus plus trastuzumab and vinorelbine in Asian patients with HER2-positive metastatic breast cancer
Authors: Toi M , Masuda N , Andre F , Ishiguro H , Fasolo A , Xu B , Jerusalem G , Shen K , Wilks S , O'Regan R , Isaacs C , Zhang Y , Taran T , Yap Y-S 
Published: August 2014

Abstract
Background: Resistance to trastuzumab may occur through activation of the PI3K/Akt/mTOR signaling pathway, the inhibition of which may restore trastuzumab sensitivity. BOLERO-3, a phase 3, double-blind, international trial involving 569 patients with trastuzumab-resistant, HER2-positive (HER2+), advanced breast cancer pretreated with a taxane, recently reported that adding everolimus (EVE; an mTOR inhibitor) to vinorelbine and trastuzumab significantly improved progression-free survival (PFS) vs placebo (PBO) plus vinorelbine and trastuzumab (hazard ratio [HR] = 0.78; log-rank P = .0067). As EVE pharmacokinetics and, therefore, clinical effects may be different in Asian patients, we analyzed the efficacy and safety data from BOLERO-3 for the Asian population.
Methods: Eligible women with trastuzumab-resistant, HER2+, advanced breast cancer who received prior taxane therapy were randomized (1:1) to EVE (5 mg/day) or matching PBO in combination with weekly vinorelbine (25 mg/m2) and trastuzumab (2 mg/kg after 4-mg/kg loading dose). The primary endpoint was PFS by investigator. Secondary endpoints included safety.
Results: Among 569 patients enrolled in this study, 166 (29%) patients were Asian; 88 and 78 were assigned to EVE or PBO arms, respectively. In this subpopulation, adding EVE to vinorelbine and trastuzumab prolonged median PFS compared with the PBO arm (8.3 vs 6.8 months, respectively; HR = 0.83; 95% confidence interval, 0.59 - 1.18). In general, the incidence of all grade adverse events was similar for Asian versus non-Asian patients in the EVE arm (stomatitis, 71% vs 59%; pneumonitis, 7% vs 5%; and infections, 58% vs 70%) and the PBO arm (stomatitis, 31% vs 26%; pneumonitis, 1% vs 4%; and infections, 48% vs 49%). Serious adverse events had a low incidence and included febrile neutropenia (9.1%), neutropenia (2.3%), stomatitis (2.3%), anemia (2.3%), and cataract (2.3%) as the most common among Asian patients in the EVE arm. The incidence of serious pneumonitis was low: Asian (1.1%) versus non-Asian patients (0%) in the EVE arm and 0% versus 1.5%, respectively, in the PBO arm.
Conclusions: Asian patients in the BOLERO-3 trial treated with EVE plus vinorelbine and trastuzumab showed PFS benefits similar to the overall population and had a comparable manageable safety profile. Thus, EVE in combination with vinorelbine and trastuzumab may be considered as a new therapeutic option for Asian women with trastuzumab-resistant, HER2+, advanced breast cancer progressing after taxane-based therapies.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-19.
Abstract P4-12-22: Time to relapse (TTR) is a potential discriminator of clinical outcome in HER2-positive breast cancer (BC) patients (pts) progressing on adjuvant trastuzumab (AdjT)
Authors: Di Cosimo S , Serpico D , Porcu L , Fanetti G , Molino L , Torri V , de Braud F 
Published: August 2014

Abstract
Background: Clinical trials for HER2-positive metastatic BC excluded pts with prior AdjT and/or relapsing within 1 year (yr) from the end of AdjT. With this gap in mind, we aimed to address the presentation, the therapeutic options, and the clinical outcome of BC pts after failure to AdjT. Methods: Medical charts of BC pts relapsing on AdjT and admitted at the National Cancer Institute of Milan were reviewed. Fisher's exact test was used for contingency tables, long-rank test for survival distribution; p&lt;0.05 was considered statistically significant. Data were matched with literature. Results: Forty pts were identified in the 2013 first quarter. Median age at relapse was 49 (26-80) yrs; 67.5% of pts had stage III; 93% neo-/adjuvant anthracycline+/-taxane; 55% hormonotherapy. Median TTR was 23.5 (5.2-108.5) months (mos). Relapses occurred during (early) or after (late) AdjT in 12 (30%) and 28 (70%) pts. Median AdjT cycles were 15 (2-18) and 18 (6-19) in pts with early and late relapses. Early and late relapses shared a similar distribution of hormone receptor positive and negative status (35% vs 25%, p = 0.73). Lung (8% vs 36%, p = 0.12), bone (25% vs 36%, p = 0.72) and multiple (8% vs 36%, p = 0.12) metastases were less likely to occur in pts with early than in late relapses; liver was affected by 42% and 29% of early and late relapses (p = 0.48). T was the 1stline tretament in 77.5% of pts. After a median follow-up of 21.3 (0.6-98.6) mos, 29 pts (72.5%) progressed. Median Time To Progression (TTP) was 12.7 (9.0-15.3) mos, with a response rate (RR) of 61%. Pts relapsing during AdjT had a shorter TTP than pts relapsing after AdjT, 9.2 (95%CI:3.9-13.3) vs 15 mos (95%CI:9.1-27.9), p = 0.048. T was the 2ndline treatment in 65.5% of pts; with a RR 51%. The literature review showed that pts with prior AdjT represent 0.9-11.7% of overall study-population in just 5 of 8 registrational trials in HER2-positive metastatic BC. No trials included pts relapsing during AdjT. Compared to pts from clinical practice, pts of the above trials were less likely to have locally-advanced BC at diagnosis and neo-/adj chemotherapy. Conclusions: T was the choice in both 1st and 2ndline treatment of pts relapsing on AdjT. Anti-tumor activity was consistent accross lines and with literature. These data should be interpreted with caution, as the cross-sectional design may have favored the inclusion of pts at good prognosis. Notwithstanding the above, pts with early relapse to AdjT showed a worse outcome as compared to the rest. Further investigation to tailor therapy for these pts is recommended. Patient data collection continues and an update will be presented at the meeting.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-22.
Abstract P5-04-16: Extracellular matrix 1 (ECM1) knockdown alters cellular characteristics, CD44 expression and other metastasis associated genes in breast cancer cells
Authors: Gomez-Contreras PC , Domann FE , Weigel RJ , Lal G 
Published: August 2014

Abstract
Introduction: ECM1 is known to be over-expressed in multiple tumor cell lines and primary tumors, including breast cancers. ECM1 overexpression is also an independent predictor of poor prognosis in primary breast carcinomas. While similar associations have also been reported in other tumors, the mechanisms by which ECM1 affects prognosis have not been elucidated.
Methods: ECM1 was silenced in the Hs578t and MDA-MB231 breast cancer cell lines using siRNA. The cells were evaluated for morphological changes, migration (wound-healing assay, TScratch program), matrigel invasion and cell attachment. Real Time RT-PCR using a 94-geneTumor Metastasis Array (TaqMan), was performed to assess the effects of ECM1 downregulation on in Hs578t cells. Alterations in RNA expression were validated at the protein level using western blots. Differences between groups were evaluated using the student's t-test and p&lt;0.05 was considered statistically significant.
Results: ECM1 silenced cells demonstrated altered morphology with a more elongated appearance to the cells, when compared those transfected with non-targeting siRNA. Reduced cell migration was noted for both silenced Hs578t and MB231 cell lines (both p&lt;0.0001). Matrigel invasion was reduced in the Hs578t cell line only (p&lt;0.002). however, cell attachment was decreased in both cell lines. (p &lt;0.0001 for Hs578t, and &lt; 0.01 for MB231). ECM1 downregulation affected the expression of several metastasis associated genes including CD44, Metalloproteinase-2, fibronectin at the RNA level. CD44 expression was significantly reduced in ECM1-silenced cells by western blot.
Conclusion: ECM1 appears to be involved in maintenance of tumor cell shape, migration, invasion and attachment properties in the cell lines tested, and also affects expression of CD44 protein, a known tumor prognostic factor. ECM1 may be a key molecule affecting tumor progression and metastasis, which is a complex process involving these components. Our findings suggest mechanisms by which ECM1 overexpression may affect tumor prognosis. Further work is needed to evaluate if altering ECM1 expression may be a novel therapeutic option for these tumors.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-04-16.
Abstract P5-05-10: Estrogenic pathways exist in TNBC and correlate with androgen receptor status
Authors: McNamara KM , Yoda T , Nurani AM , Miki Y , Suzuki T , Nemoto N , Miyashita M , Tamaki K , Ishida T , Ohuchi N , Sasano H 
Published: August 2014

Abstract
Triple negative carcinoma are a difficult to treat subtype of carcinomas due to the fact they do not express any of the markers at which targeted therapy is directed at such as ER, PR or HER2. Traditionally these carcinomas are referred to as estrogen receptor negative, however in reality the assessment of ER expression is limited to the ERa form; evaluation of ERβ expression in TNBC has been, on the whole, overlooked. A limited number of studies have suggested that in a large proportion of TNBC ERβ continues to be expressed. In this study we chose to focus on the ERβ1 subtype, as this has been previously suggested to be associated with a positive prognosis in TNBC. We sought to examine if there was an overlap between androgen receptor, ERβ1 and AKR1C3 (17βHSD5) expression as these have been suggested, at least in the prostate, to form a steroid metabolism pathway via which the inactivation of androgen can generate estrogenic signals. In addition we also assessed the presence of the canonical pathway of estrogen metabolism via intratumoral aromatase to see if this had a potential biological role in breast cancer.
Following appropriate IRB approval a cohort of 78 samples of triple negative invasive ductal carcinoma from Tohoku University Hospital were collected. These samples were stained for ERβ1 and aromatase. ERβ1 samples were classified as positive or negative using a 10% labelling index criteria while aromatase was classified as positive if greater that 50% of carcinoma cells showed immunoreactivity. The expression pattern of both stains was then compared to a historical set of data regarding AR, AKR1C3 (17βHSD5 staining) and Ki67. In this comparison ERβ1 positivity and aromatase positivity was significantly and positively associated with AR positivity (Chi squared test p &lt;0.01). ERβ1 however showed no relationship to either aromatase expression or 17βHSD5 expression. While both stains showed a trend towards lower Ki67 labelling indexes in conjunction with higher immunoreactivity, neither was significant. In a standard least squares model incorporating AR, ERβ1, 17βHSD5 and AROM positivity was the only factor that had an independent significant effect on Ki67 labelling index was that of AR positivity (Model p&lt;0.05, AR effect p&lt;0.01) with, as we have previously shown, AR positivity being associated with lower Ki-67 labelling index.
These results suggest that while estrogenic pathways remain in TNBC, the dominant steroid metabolism pathway is that of the androgen receptor. However, further research is warranted to fully understand the roles of estrogenic pathways in triple negative disease.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-05-10.