bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-07-48: Prediction of complete pathologic response to veliparib/carboplatin plus standard neoadjuvant therapy in HER2 negative breast cancer: Exploratory protein pathway marker results from the I-SPY 2 trial
Authors: Wulfkuhle JD , Yau C , Wolf DM , Gallagher RI , Deng J , Brown-Swigart L , Hirst G , I-SPY 2 Trial Investigators , Rugo H , Olopade OI , Esserman L , Berry D , van't Veer L , Petricoin EF 
Published: May 2016

Abstract
Background: In the I-SPY 2 TRIAL, HER2- patients were randomized to receive standard chemotherapy or chemotherapy plus the oral PARP inhibitor veliparib in combination with carboplatin (V+C), which graduated in the HR-/HER2- arm. Exploratory analysis of protein signaling was performed to identify biomarker candidates that correlated with pCR in the HER2- population. We evaluated 110 key signaling proteins using reverse phase protein microarray (RPPA) data from pre-treatment LCM purified tumor epithelium.
Methods: Of 115 patients, 97 (V+C: 61 controls: 36) had RPPA and pCR data. RPPA data was correlated to pCR in both the treated and control patients using parametric (t-test) or non-parametric (Wilcoxon) statistical analysis, depending on data distribution. Only analytes whose pre-treatment levels were associated with response in the V+C but not the control arm were identified (P&lt;0.05). Markers are analyzed individually; p-values are descriptive and were not corrected for multiple comparisons.
Results: 11 protein/phosphoprotein markers were significantly associated with pCR in the V+C arm but not in controls. Two were positive predictors of response: YAP S127 p= 0.03 and LC3B p=0.04. Negative predictors of response included Cyclin D1 p=0.001, and a number of phosphorylated RTKs: ROS Y2274 p=0.03, IGF1R Y1135/Y1136-IR Y1150/Y1151 p=0.03, ERBB4 Y1284 p=0.002, total HER2 p=0.04, and total IGF1R p=0.01. Moreover, a number of AKT-mTOR pathway proteins were found to be negative predictors of V+C response: ACC S79 p=0.005, p70S6K S371 p=0.01, and B-RAF S445 p=0.01.
Conclusion: Our sample size is too small to draw definitive conclusions and the results are exploratory. Coordinated RTK-mTOR pathway activation appears to be a hallmark signature of lack of response to veliparib in HER2- tumors. We also found that HER2 levels were correlated paradoxically with lack of response in this HER2- population, suggesting potential added clinical value of quantitative HER2 measurement techniques. Such exploratory results merit evaluation in larger trials with HER2- breast cancer patients.
Citation Format: Wulfkuhle JD, Yau C, Wolf DM, Gallagher RI, Deng J, Brown-Swigart L, Hirst G, I-SPY 2 Trial Investigators, Rugo H, Olopade OI, Esserman L, Berry D, van't Veer L, Petricoin EF. Prediction of complete pathologic response to veliparib/carboplatin plus standard neoadjuvant therapy in HER2 negative breast cancer: Exploratory protein pathway marker results from the I-SPY 2 trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-48.
Abstract P3-07-63: Ki67 cut-off point to predict the benefit of adjuvant chemotherapy in ER+ HER2- breast cancer patients
Authors: Rouzier R , Rossi L , Lerebours F , Savignoni A , Falcou M-C , Bonneau C , Pierga J-Y , Guinebretière J-M 
Published: May 2016

Abstract
BACKGROUND: The benefit of chemotherapy for patients with estrogen receptor(ER)+ HER2- breast cancers is an ongoing question. The evaluation of the tumor's proliferation by Ki67 may guide the indication but no consensual predictive cut-off has been set yet.
MATERIALS AND METHODS: This study included women with a first ER+HER2- invasive breast cancer treated by primary surgery between 2003 and 2008. Data was collected prospectively. Ki67 cut-off was sequentially set each 1% from 5% to 30%. For each threshold, the interaction between Ki67 and adjuvant chemotherapy was integrated in a multivariate Cox model to determine when it became statistically significant in predicting distant-disease free survival (DDFS). Using different Ki67 cut-offs, we also compared DDFS of patients who had or not an indication of chemotherapy, depending on whether they actually received it or not.
RESULTS: Among the 3221 breast cancers, median Ki67 was 10%, with a mean of 15% (S.D = 14). Ki67 was an independent prognosis factor whether the cut-off was set to 14% or to 20% (p&lt;0.001). The interaction between Ki67 and chemotherapy became significant only for a threshold of Ki67 above 20% (p&lt;0.05). When adjuvant chemotherapy was not indicated according to St Gallen guidelines 2013 with a Ki67 cut-off set to 20%, DDFS was not significantly improved if patients did receive chemotherapy.
CONCLUSION: In ER+ HER2- breast cancers, a Ki67 level of expression &gt;= 20% was predictive of benefit from adjuvant chemotherapy. A threshold at 14% was not as discriminant. Based on this large cohort study, we recommend the use of a cut-off at 20% to decide whether patientes with ER positive tumors should receive chemotherapy or not/.
Citation Format: Rouzier R, Rossi L, Lerebours F, Savignoni A, Falcou M-C, Bonneau C, Pierga J-Y, Guinebretière J-M. Ki67 cut-off point to predict the benefit of adjuvant chemotherapy in ER+ HER2- breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-63.
Abstract P3-12-20: The impact of everolimus on radiation-induced pulmonary fibrosis in wistar albino rats: Results of an experimental study
Authors: Eren MF , Ay Eren A , Yücel B , Elagöz S , Özgüven Y , Altun A , Kiliçkap S , Matsuno R , Bese N 
Published: May 2016

Abstract
Objectives:
This study was performed to evaluate the effects of everolimus on pulmonary fibrosis, given concurrently or sequential with irradiation in rats.
Materials and Methods:
Forty female Wistar albino rats were randomized into five groups. The first group (Group 1: sham) was observed with identical conditions of the animals in other groups. The second group (Group 2) had only everolimus application. The third group (Group 3) had thoracic irradiation first and they had everolimus injection 22 hours after radiotherapy. The fourth group (Group 4) had irradiation to whole thoracic region in 2 hours of following everolimus administration. The last group (Group 5) had irradiation to whole thoracic region. As an end point the percentage of lung with fibrosis for each rat was quantified with image analysis of histological sections of the lung. Groups were compared using the linear regression method, Fisher's exact and chi-square tests were used to assess the association between treatment groups.
Results:
There was a statistically significant difference in the distribution of fibrosis scores among all groups (p=0.0022). Linear regression analyses revealed that all treatment groups showed an increased risk of lung fibrosis compared to control group. Group 2 (p=0.0020), group 3 (p&lt;0.0001), group 4 (p&lt;0.0001), and group 5 (p=0.0002). Chi-square test demonstrated that there was no statistically significant difference between the sequentially and concurrent treatment groups.
Conclusion:
This experimental study showed that of everolimus by itself may lead pulmonary fibrosis and addition to radiotherapy either sequentially or concomitantly increased the severity of the lung damage in rats.
Keywords: Radiotherapy, everolimus, rats, pulmonary fibrosis.
Citation Format: Eren MF, Ay Eren A, Yücel B, Elagöz S, Özgüven Y, Altun A, Kiliçkap S, Matsuno R, Bese N. The impact of everolimus on radiation-induced pulmonary fibrosis in wistar albino rats: Results of an experimental study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-20.
Abstract P3-14-12: Phase 0 study evaluating COX2 inhibition on circulating PGE2 levels from obese subjects
Authors: Lengfelder L , Brenner A , Bowers L , Apte S , Galván G , Kist K , deGraffenried L 
Published: May 2016

Abstract
Introduction: Obesity is associated with poor breast cancer outcomes in postmenopausal women in response to aromatase inhibitor therapy. Our prior studies have shown an association between reduced recurrence rate and use of cyclooxygenase-2 (COX-2) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) in obese breast cancer patients. The mechanism proposed was a decrease in prostaglandin E2 (PGE2) and reduced activation of the aromatase promote locally in the breast.
Methods: Postmenopausal women of varying body habitus were recruited at the CTRC in San Antonio and underwent randomized assignment to 1 of 3 arms: ASA 81mg daily, 1500mg of docosahexaenoic acid (DHA) and 2500mg eicosapentaenoic acid (EPA) given daily, or combined ASA and DHA/EPA. Sera were collected prior to and following 28 days of exposure, and cytokines including prostaglandin E2 were assessed via enzyme-linked immunosorbant assay (ELISA). Conditioned media was generated by exposing macrophages to patient sera in order to see if the patient sera induced PGE2 concentration in vitro.
Results: Thirty of the planned 120 subjects have completed assessment. No toxicity has been noted. In 71% of the patients, serum PGE2 levels decreased, but only 60% demonstrated concurrent decrease in serum PGE2 levels as well as macrophage PGE2 production, while almost all (88%) of the patients whose serum did not demonstrate a decrease in PGE2 levels also demonstrated no decrease in induced levels.
Conclusion: NSAIDs appear to effectively decrease circulating levels of PGE2 in most obese women. However, one third of the subjects did not demonstrate concurrent suppression of induced PGE2 from macrophages. These data suggest that circulating levels of PGE2 may not be reflective of local tumor microenvironment levels, and other pro-inflammatory circulating factors may be responsible for regulating local inflammatory responses. Final analysis will be completed and presented at the SABCS meeting.
Citation Format: Lengfelder L, Brenner A, Bowers L, Apte S, Galván G, Kist K, deGraffenried L. Phase 0 study evaluating COX2 inhibition on circulating PGE2 levels from obese subjects. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-14-12.
Abstract P4-01-03: Digital measurement of mammographic density and the risk of overlooking cancer in Japanese women
Authors: Sawada T , Ikeda M , Kuwayama T , Akashi ST , Nakamura S 
Published: May 2016

Abstract
Introduction: mammographic density is a strong risk factor for breast cancer and an essential determinant of screening sensitivity, but the breast density of Japanese women has yet to be objectively examined. Single mammographic examination fails to detect approximately half of breast cancers in women with dense breasts. We objectively evaluated mammographic density to clarify the relation between breast density and incidence of breast cancer in Japanese women.
Method: We enrolled 269 patients diagnosed with breast cancer and 397 healthy controls, who participated in screening mammography at Showa University Hospital. Breast density was measured using Volpara (a software application which analyses breast composition volumetrically).
Results:
The average age of both control and breast cancer groups was 55. Of the control group, 308 (78%) were characterized as having dense breasts, being defined as volumetric density grade (VDG) 3 or 4. More than 50% of the total population (all ages) had dense breasts (VDG 3 or 4) and more than 20% were extremely dense (VDG:4). Of the breast cancer patients, 232 (87%) were VDG 3 or 4. 52 (23%) of those with dense breasts showed negative results in single mammography examination. In primary breast cancer patients with dense breasts, 30% of those under age 70, but only 13% of those over age 70, showed no abnormal findings from mammographic examination.
Conclusion and Discussion: In comparison of our present results and other papers, In the Japanese control group, 72% of patients had dense breasts (VDG 3 or 4) at age 50 or greater, but in Holland, for example, only 36% of women had breasts classed as dense. 87% of Japanese women with breast cancer had dense breasts, approximately the same ratio (88%) as found in Korea. For Japanese and other Asians, women under 70 years old with dense breasts may warrant additional screening.
Citation Format: Sawada T, Ikeda M, Kuwayama T, Akashi ST, Nakamura S. Digital measurement of mammographic density and the risk of overlooking cancer in Japanese women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-01-03.
Abstract P4-02-13: The pattern of tumor shrinkage is associated with prognosis in low grade luminal early breast cancer during neoadjuvant chemotherapy
Authors: Fukada I , Araki K , Kobayashi K , Gomi N , Horii R , Akiyama F , Takahashi S , Iiwase T , Ohno S , Ito Y 
Published: May 2016

Abstract
BACKGROUND: In neoadjuvant chemotherapy (NAC) for early breast cancer, the pathological response rate in estrogen receptor (ER)-positive tumors has been low in comparison with those of ER-negative tumors. Therefore, surrogate makers other than the pCR rate are needed during NAC for luminal breast cancer. Using MRI, we analyzed the patterns of tumor shrinkage after NAC as a surrogate prognostic factor in low grade luminal breast cancer. METHODS: Of 854 patients who had received NAC in a single institute from Jan. 2000 to Dec. 2009, 183 patients with low grade luminal breast cancer were retrospectively evaluated for this study. They were defined as ER and/or PgR positive in more than 10% of cancer cells and HER2 negative (IHC 0, 1+ or FISH &lt;2.0) with nuclear grade 1 and 2. RESULTS: The median observation period was 67.9 months following surgery, and recurrence was observed in 31 patients (16.9%). The median age was 49 (22-76) years. One hundred eighty patients received anthracycline-containing chemotherapy, and 158 received taxane. There were 16 deaths (8.7%) related to breast cancer. We categorized the patterns of tumor shrinkage by MRI into 6 types: concentric shrinkage (CS), diffuse decrease (DD), reduction to small foci (RSF), decrease of intensity only (DIO), no change (NC), and enlargement (EL). According to our categorization, CS occurred in 97 (53.0%), RSF in 7 (3.8%), DD in 62 (33.9%), DIO in 7 (3.8%), NC in 5 (2.7%), and EL in 5 (2.7%). As expected, there were statistically significant differences in both the median DFS and OS in each pattern of tumor shrinkage (p &lt;0.001 and p=0.001, respectively); in particular, the CS pattern had excellent prognosis. Multivariate analysis demonstrated that concentric shrinkage was the only significant good prognostic factor for OS (p=0.015). CONCLUSIONS: Tumor shrinkage patterns as revealed by MRI could be important surrogate prognostic factors for NAC in early low grade luminal breast cancer.
Citation Format: Fukada I, Araki K, Kobayashi K, Gomi N, Horii R, Akiyama F, Takahashi S, Iiwase T, Ohno S, Ito Y. The pattern of tumor shrinkage is associated with prognosis in low grade luminal early breast cancer during neoadjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-02-13.
Abstract P4-03-06: Near-infrared diffuse optical imaging for early prediction to neoadjuvant chemotherapy in patients with primary breast cancer
Authors: Ogura H , Yoshizawa N , Ueda S , Hosokawa Y , Matsunuma R , Tochikubo J , Nasu H , Shigekawa T , Takeuchi H , Osaki A , Saeki T , Yoshimoto K , Ohmae E , Suzuki T , Ueda Y , Yamashita Y , Sakahara H 
Published: May 2016

Abstract
Background: Diffuse optical spectroscopic imaging (DOSI) can be exploited as a marker of tumor blood volume quantified by tissue hemoglobin (tHb) concentration. In DOSI, frequent measurement is possible for breast cancer patients because of its non-invasiveness. The tHb concentration determined by DOSI is expected to be a new biomarker for prediction of breast cancer response to neoadjuvant chemotherapy (NAC).
Purpose: Our objective is to determine whether early change of tumor tHb concentration predicts pathological complete response (pCR) to NAC in patients with operable breast cancer.
Methods: In a prospective study, one hundred patients with primary breast cancer were enrolled for primary objective analysis. The regimens of NAC were according to the standard of care. Patients underwent sequential scans using DOSI at baseline, after 1st course and 2nd course of chemotherapy. The mean value of tHb (tHbmean) concentration of the targeted lesion was measured and the percentage change in tHbmean (ΔtHbmean) concentration was calculated. Receiver operating curve analysis demonstrated diagnostic performance of DOSI for predicting a pCR.
Results: In interim analysis, it was regarded as a good outcome that area under the curve (AUC) for ΔtHbmean after 1nd course was 0.797 (SE 0.104, 95%CI 0.633-0.911), and after 2st course was 0.867 (SE 0.06, 95%CI 0.715-0.956).
Conclusion: DOSI could predict accurately a pCR to neoadjuvant chemotherapy in patients with primary breast cancer.
Citation Format: Ogura H, Yoshizawa N, Ueda S, Hosokawa Y, Matsunuma R, Tochikubo J, Nasu H, Shigekawa T, Takeuchi H, Osaki A, Saeki T, Yoshimoto K, Ohmae E, Suzuki T, Ueda Y, Yamashita Y, Sakahara H. Near-infrared diffuse optical imaging for early prediction to neoadjuvant chemotherapy in patients with primary breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-03-06.
Abstract P4-04-02: Amplification of chromosome 9p24 targeting PD-L1 and JAK2 correlates with altered tumor microenvironment expression profiles in triple negative breast cancer
Authors: Anderson KS , Andreozzi M , Pockaj BA , Hopper M , McCullough AE , Barrett MT 
Published: May 2016

Abstract
Introduction: In a pilot study, we recently described amplification of chromosome 9p24 encoding PD-L1, PD-L2, and JAK2 (the PDJ amplicon) in 29% of early stage triple negative breast cancers (TNBC). Amplification was associated with poor DFS and OS. The impact of this amplicon on immune function is not known.
Methods: Fresh frozen tumor samples from 36 subjects with newly-diagnosed TNBC (stages I-III) were evaluated for copy number aberrations using DNA-based flow cytometry to enrich nuclei based on ploidy status (tetraploidy or aneuploidy), followed by oligonucleotide CGH arrays. Targeted immune expression profiling was performed using the Nanostring PanCancer Immune Profiling Panel (n=770 genes).
Results: 23 samples had measurable abnormal ploidy (evidence of sufficient tumor content) for CGH analysis; the remaining samples were omitted from analysis. High level (log2ratio &gt;1) amplification was detected in 6/23 (26.1%) of TNBCs, and low-level copy number gain (CN log2ratio &gt;0 and&lt;1) was detected in 3/23 (13.0%). The remaining samples had no copy number change (n=9) or low level copy number loss (CN log2ratio&gt;-1 and &lt;0, n=5). Increased RNA expression of STAT1, STAT2, STAT3, and STAT6 was associated with PDJ amplification, as well as upregulation of the immune regulatory genes CD47 and IDO1.
Conclusion: Amplification of chromosome 9p24.1 involving PD-L1, PD-L2, and JAK2 is present in a significant proportion of TNBCs. This amplicon is associated with altered gene expression of the tumor microenvironment.
Citation Format: Anderson KS, Andreozzi M, Pockaj BA, Hopper M, McCullough AE, Barrett MT. Amplification of chromosome 9p24 targeting PD-L1 and JAK2 correlates with altered tumor microenvironment expression profiles in triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-02.
Abstract P4-04-13: Comparison of tumor and stroma CD73 expression with TLR9 and survival in breast cancer
Authors: Selander K , Mella M , Kauppila J , Karihtala P , Jukkola-Vuorinen A , Auvinen P , Soini Y , Kauppila S , Haapasaari K-M , Harris K , Vuopala K 
Published: May 2016

Abstract
CD73 is a 5' ectonuclease that catalyzes the conversion of cyclic AMP into the highly immunosuppressive adenosine in extracellular space. In addition to the cells of the immune system, CD73 is highly expressed in various cancer cell lines and clinical cancer tissues. Toll like receptor-9 (TLR9) is a cellular DNA-receptor that is highly expressed in breast cancer. Both CD73 and TLR9 expression have recently been associated with TNBC prognosis but the mechanisms how these proteins possibly contribute to TNBC pathophysiology remains poorly understood. TLR9 and CD73 expression has been shown to be mutually regulated in various cell types. Whether this is the case in cancer is unknown. The aim of this study was to investigate the mutual role of TLR9 and CD73 in breast cancer (BC). Specifically our hypothesis was that TLR9 and CD73 expression correlate in TNBC. We compared immunohistological tumor TLR9 and CD73 expression scores using a previously characterized breast cancer (BC) cohort (n=184) with follow-up time of &gt; 10 years. We did not discover a connection between TLR9 and CD73 expression in tumor cells in BC. There was a trend for increased survival among patients that had high tumor cell CD73 expression, as compared with the lower tumor cell CD73 expression groups. There was a trend for a better survival among TNBC patients that had lower stromal CD73 expression, as compared with those TNBC patients that had higher stromal CD73 expression. No such difference was detected among patients with non-TNBC tumors. Our results suggest that stromal vs. tumor cell CD73 expression have opposite effects on survival in TNBC, but there is no connection between CD73 and TLR9 expression. Our conclusions are limited by low sample numbers.
Citation Format: Selander K, Mella M, Kauppila J, Karihtala P, Jukkola-Vuorinen A, Auvinen P, Soini Y, Kauppila S, Haapasaari K-M, Harris K, Vuopala K. Comparison of tumor and stroma CD73 expression with TLR9 and survival in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-13.