bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-09-06: The structure design and biological activities of inhibitory peptides, which block the interactions among polycomb repressive complex 2
Authors: LI KK , Luo L , Kong X , Li L , Luo C 
Published: August 2014

Abstract
Polycomb repressive complex (PRC2) contains several proteins, including embryonic ectoderm development (EED), suppressor of zeste 12 (SUZ12) and enhancer of zeste homolog 2 (EZH2). Excessive EZH2 concentrations have been reported as a marker of aggressive breast cancer and associated with invasion and cancer progression. EZH2 levels were elevated in patients with invasive breast carcinoma relative to normal or atypical hyperplasia. Except for the C-terminal SET domain, which functions as a histone-lysine N-methyltransferases, EZH2 has an N-terminal alpha helix region, which forms tight complex with EED protein. The in vivo enzymatic activity of EZH2 relies on and be tightly regulated by the interaction with EED. We designed series of artificial peptides trying to block the interaction between EZH2 and EED. By using label-free surface plasmon resonance (SPR) technology, the dynamic binding capacities of these peptides were tested. There were 3 leading structures standing out from the screening of more 80 peptides. After several round of co-crystal structure based optimization, the binding capacity of one inhibitor was reached to several nM levels, which indicated the availability for being a drug candidate. Finally, the biological activities of the inhibitory peptides were tested in several breast cancer cell lines. The PRC2 inhibitory peptides in this study are the first time reported PRC2 targeting epigenetic molecules with biological activity in breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-09-06.
Abstract P2-10-04: The Mammostrat Test is an Effective Tool to Stratify Patient Samples Previously Characterized as Intermediate by the Oncotype Dx Test
Authors: Bloom KJ , Kyshtoobayeva A , Hilaire L , Gutekunst K 
Published: August 2014

Abstract
Mammostrat is a well validated, 5-antibody immunohistochemistry (IHC) based assay initially developed to assess the risk of recurrence in patients with early stage estrogen receptor (ER) positive breast cancer. Recent data from the TEAM trial demonstrated that Mammostrat predicted distant relapse free survival (DRFS) for both exemestane and tamoxifen-exemestane treated patients irrespective of nodal status and chemotherapy. OncoType Dx® is a recurrence assay frequently used by oncologists to aid in the selection of early stage breast cancer patients who may benefit from adjuvant chemotherapy. It is currently unclear whether patients whose tumors demonstrate an intermediate risk score should receive chemotherapy. We sought to determine if tumors with intermediate OncoType Dx® scores would be clearly classified as high or low risk with the Mammostrat assay.
Formalin fixed paraffin embedded tissue blocks were retrieved from 143 patients whose tumor were previously assessed as intermediate with the OncoType Dx® assay (Genomic Health, Redwood City, Ca). Six serial 5 micron sections were cut from the tissue block. One section was stained with H&E and the remaining five sections were stained with the Mammostrat antibodies, NDRG1 (AGI-3-3-12E clone, Clarient, Aliso Viejo, CA), TRMT2A (AGI-2-33-12E clone, Clarient, Aliso Viejo, Ca), P53 (D07 clone, Dako, Carpenteria, CA), CEACAM (S0235 08/28/06 clone, Clarient, Aliso Viejo, CA)and SLC7A5 (AGI-1-108-2E clone, Clarient, Aliso Viejo, CA). Slides were reviewed by a single pathologist (KJB) using previously published Mammostrat criteria and a risk score of low, moderate or high was generated.
Of the 143 tumors, 62 (43%) were classified as low risk, 51 (36%) were classified as high risk and 30 (21%) were classified as moderate risk. Thus, 113 (79%) cases were defined as either low risk or high risk by the Mammostrat assay.
The Mammostrat assay reclassified 79% of OncoType Dx® intermediate tumors into a clear high risk or low risk category. Based on data from the TEAM trial, node negative patients categorized as low risk by Mammostrat had a 5 year DRFS of 96%, while data from the NSABP-B20 trial showed that patients categorized as high risk by the Mammostrat assay derived a significant benefit from adjuvant chemotherapy. Mammostrat may be an effective tool to aid oncologists and patients in treatment decisions when Oncotype Dx® classifies a tumor as intermediate risk.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-04.
Abstract P2-10-05: Continuous association of a 200-gene prognostic risk score with probability of neoadjuvant chemotherapy response and translation from fresh frozen to FFPE tissue for clinical use.
Authors: van Laar R , DiPaola J , Carbaugh H , Murphy T , DiRamio A , Flinchum R , Brown N , Albino T 
Published: August 2014

Abstract
BreastPRS is a suite of complimentary gene signatures that resolves several of the significant limitations of current gene expression signatures in breast cancer. Notably, BreastPRS can accurately provide prognosis prediction, histological grade resolution and molecular subtyping of invasive breast cancer. The 200-gene prognostic component was previously validated in an independent retrospective series of 1,016 previously published fresh-frozen breast cancers and has now been applied to data from over 6,000 patients.
In part one of this study, a meta-analysis of 890 previously published neoadjuvant treated breast cancer patients was performed. A highly significant association was observed between prognosis risk group (high vs low), continuous risk score (0–100), and a patient's probability of achieving complete pathologic response with neoadjuvant chemotherapy. Data from both fine-needle-aspirate and biopsy tissue were included in the cohort. Notably, fewer than 10% of patients with the lowest (most favorable) pre-treatment BreastPRS prognosis scores achieve pCR. Probability of pCR was observed to increase steadily to over 40% for individuals with the highest prognosis scores.
In part two of the analysis, 50 paired fresh-frozen and FFPE tumors were profiled on whole genome microarrays containing all three signatures, in a CLIA-certified high throughput genomics laboratory. Results will be presented that highlight the consistency of the prognosis, grade and subtype signatures in clinically relevant FFPE tissue.
This suggests that BreastPRS, in addition to identifying 10-year recurrence risk, histologic grade and molecular subtype, may enable physicians to determine a patients benefit from receiving neoadjuvant chemotherapy with more granularity than current clinical or genomic methods.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-05.
Abstract P2-10-21: Prognostic value of estrogen receptor status in women with synchronous or metachronous breast cancers
Authors: Huo D 
Published: August 2014

Abstract
Background: Estrogen receptor (ER) is an important prognostic and predictive factor for breast cancer (BC) patients. For women with two primary breast cancers, however, estrogen receptor status measured at the two tumors is not always the same, either due to tumor heterogeneity, or because of limited reproducibility of receptor assays. For women with metachronous breast cancers, it is unclear if estrogen receptor status of previous cancer has prognostic value. For women with synchronous breast cancers, it is important to know if inconsistent receptor status predicts worse clinical outcome.
Methods: Data on ER status of two primary breast cancers were obtained from the Surveillance, Epidemiology, and End Results program 1990–2009. We used piecewise proportional hazard Cox models to examine the joint effect of ER statuses of two tumors on overall survival or disease-free survival. Hazard ratio (HR) and 95% confidence interval (CI) were calculated, after adjusting for age, stage, race/ethnicity, histology, grade, and treatments in Cox models. Synchronous and metachronous cases were analyzed separately.
Results: There are 12,285 patients with synchronous breast cancers; 81.2% had both tumors being ER positive, 10.2% had one tumor being ER positive but the other being ER negative, and 5.6% had both tumors being ER negative. As shown in the Table, patients with inconsistent ER status (heterogeneity) had worse short-term survival rate than patients with double ER positive tumors. Among the 14,470 patients with metachronous breast cancers, 60.2% had two ER+ tumors, 13.8% had two ER− tumors, 11.8% had ER status changing from negative to positive, and 14.1% had ER status changing from positive to negative. In addition to ER status of the index cancer, ER status of the first cancer has independent prognostic value in predicting both short-term and long-term outcome (p = 0.0002).

Conclusions: Our study found that estrogen status of previous cancer has independent prognostic value for women with metachronous breast cancers. We also found that inconsistency in ER status between two tumors predicts worse survival for women with synchronous breast cancer. These findings suggest that heterogeneity or change in estrogen receptor expression in patients with two breast cancers should be considered during decision making on treatment or counseling on prognosis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-21.
Abstract P2-10-26: Association between circulating tumor cells and molecular breast cancer subtypes
Authors: Gang N , Haibo W , Funian L , Chen L , Xiaoyi L , Xingang W , Zhidong L 
Published: August 2014

Abstract
Background and Objective: Circulating tumor cells (CTCs) provide crucial information for the management of breast cancer patients. CTCs analysis can be used as a liquid biopsy approach for prognostic and predictive purposes in breast and other cancers. Several contradictory results presented about the breast cancer subtypes of CTCs recently. The aim of this study was therefore to analysis the association between the CTCs and molecular breast cancer subtypes.
Methods: Blood samples were obtained from 143 breast cancer patients admitted to Breast Surgery Department, Affiliated Hospital of Medical College, Qingdao University. CTCs were detected by using immunomagnetic enrichment and a commercial kit, based on RT-PCR, was used to characterize CTCs. The expression of ER, PR, HER2 was detected by immunohistochemistry. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2−), luminal B (ER+ and/or PR+, HER2+), TNBC (ER−, PR−, HER2−), and HER2+, (ER−, PR−, and HER2+). The relations between the positive rate of CTCs and clinicopathological characteristics of primary tumor and molecular subtypes of breast cancer patients were analyzed.
Results: Overall positive rate of CTCs was 39.8% (57/143). The positive rate of CTCs in patients with Luminal A, Luminal B, HER2+ and TNBC subtype was 33.8% (26/77), 47.1% (8/17),50.0% (6/12) and 45.9%(17/37). There was significant difference in positive rate of CTCs by different molecular subtypes (P = 0.0415), especially at different AJCC stages (P = 0.004). The positive rate of CTCs in patients with Luminal A subtype was significantly lower than patients with the others breast cancer subtypes (p = 0.0387).
Conclusion: Our study suggests that presence of CTCs was more frequently found in patients with HER2+ and Luminal B subtypes. The presence of CTCs in patients with TNBC subtype was not as high as we wished. Theoretically, the positive rate of CTCs in TNBC subtype should be higher than that of others subtypes for being more aggressive histologically features and having increased potential to be invasive. One possible explanation for this might because of lacking epithelial markers expression and epithelial-mesenchyme transition (EMT) characteristics, CTCs of TNBC subtype are missed when using the standard EpCAM-based method. Shortage of patient's number was another possible reason. Further research on the Association between CTCs and molecular breast cancer subtypes will contribute to a better understanding of the biology of metastatic development in cancer patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-26.
Abstract P2-10-28: The Prognostic Index, KiGE, Combining Proliferation, Histological Grade and Estrogen Receptor Status Challenges Gene Profiling – A Study in 1,854 Chemo-Naïve Women with N0/N1 Primary Breast Cancer.
Authors: Strand C , Bak M , Borgquist S , Chebil G , Falck A-K , Fjällskog M-L , Grabau D , Hedenfalk I , Jirström K , Klintman M , Malmtröm P , Olsson H , Rydén L , Stål O , Bendahl P-O , Fernö M 
Published: August 2014

Abstract
Purpose: The aim was to validate the prognostic value of a previously defined index (CAGE), combining proliferation (Cyclin A), histological grade, and estrogen receptor (ER) in different subsets of primary breast cancer patients. In the present study, Ki67 was included in the index (KiGE) instead of cyclin A, since it is the generally accepted proliferation marker in clinical routine.
Patients and methods: 1,854 chemo-naive patients with primary breast cancer were included. The low KiGE group consisted of histological grade 1 cases and grade 2 cases which were ER-positive and had low Ki67 expression. High KiGE consisted of all other cases.
Results: The KiGE index separated patients into groups with different prognosis. In multivariate analysis, KiGE was significantly associated with disease-free survival, when adjusted for age at diagnosis, tumor size and adjuvant endocrine treatment (hazard ratio: 3.5, 95% confidence interval: 2.6–4.7, P&lt;0.0001).
Conclusion: We have validated a prognostic index based on proliferation (Ki67), histological grade and ER, for identification of a low-risk group of patients with N0/N1 primary breast cancer. For this low-risk group, with a five-year distant disease-free survival of 92%, adjuvant chemotherapy will have limited effect and may be avoided. The KiGE index, based on clinically used factors, may challenge the more expensive gene expression profiles.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-28.
Abstract P2-10-30: Expression of lipid metabolism genes in contralateral unaffected breast associated with estrogen receptor status of breast cancer
Authors: Wang J , Scholtens D , Holko M , Ivancic D , Lee O , Hu H , Chatterton RT , Khan SA 
Published: August 2014

Abstract
Background: Risk biomarkers that are specific to ER subtypes of breast cancer would help developing distinct prevention strategies. The contralateral unaffected breast of women with unilateral breast is a good model for defining subtype specific risk as women with ER− primary tumor are at high risk for subsequent ER− tumor in contralateral breast.
Methods: We performed random fine needle aspiration of unaffected breast of cases. RNA samples from 30 subjects (15 ER+ and 15 ER−) were used for Ilumina expression array analysis. Findings were validated by qRT-PCR using independent sample set consisted of 36 subjects (12 ER+, 12 ER−, and 12 standard risk healthy controls).
Results: Gene array studies identified 18 genes with significant higher expression in ER− case samples, 8 of which were associated with lipid metabolism. This pattern was confirmed by qRT-PCR in the same samples and in the 24 cases of validation set. When compared to the healthy controls, significant over-expression of 4 genes (DHRS2, HMGCS2, HPGD, ACSL3) was observed in ER− cases, with significant lower expression of UGT2B11 and APOD in ER+ cases, and decreased expression of UGT2B7 in both subtypes.
Conclusion: Differential expression of lipid metabolism genes my be involved in the risk for subtypes of breast cancer, which might be potential biomarkers of ER specific breast cancer risk.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-30.
Abstract P2-10-36: Analysis of biomarker expression and biological subtype in primary tumour, corresponding lymph node and distant metastasis with 5-year follow-up
Authors: Falck A-K , Ferno M , Bendahl P-O , Chebil G , Olsson H , Rydén L 
Published: August 2014

Abstract
Background: Biological variation in genotype and phenotype of primary breast cancer explains the heterogeneity of the disease and subsequent outcome. Choice of treatment is routinely based on the biomarker expression of the primary tumour with regard to estrogen- (ER) and progesterone (PR) receptor status, human epidermal growth factor receptor 2 (HER2) status and the proliferation marker Ki67, individually. Recently, gene expression profiling and subsequent immunohistochemical studies have identified biologically distinct subtypes by using a combination of biomarkers which have been shown to be of prognostic value beyond the previous known. However, tumour progression theories propose a change in biomarker expression during development from primary tumour to distant metastasis with implications on choice of therapy. The aim of this study was to compare biomarker expression individually and according to biological subtype between tumour samples from primary tumour, lymph node metastasis and distant metastasis from the same patient.
Material and methods: From an original cohort of 569 patients with primary breast cancer, tissue microarrays were constructed from archival tissue blocks of primary tumour (n = 521), paired lymph node metastasis (n = 147) and biopsies from distant metastasis (n = 42). The samples were evaluated by two independent pathologists. The individual biomarker expression as well as subtype classification (Luminal A: ER+ and/or PR+, Ki67≤ 20% and HER2−. Luminal B: ER+ and/or PR+, Ki67&gt; 20% and/or HER2+. HER2 type: ER/PR−, HER2+. Basal-like: ER/PR−, HER2−, CK5/6+ and/or EGFR+) were compared between primary tumour, lymph node metastasis and distant metastasis. Survival outcome were estimated using the Kaplan-Meier method and log rank test. The primary end-point was distant disease-free survival (DDFS).
Results: Distribution according to subtype.

The molecular subgroups in the primary tumours were associated with statistically significant prognostic information by log-rank test (p = 0.005) validating luminal A as a subgroup with excellent prognosis. More detailed survival analysis comparing expression of biomarkers between primary tumour, lymph node metastasis and distant metastasis will be presented.
Conclusion: Prognostic information can be obtained by subtype classification using routine-based biomarker analysis in the primary tumour. Preliminary data suggest that the subtype distribution is associated with a worse prognostic profile in the lymph node- and distant metastasis. Detailed survival analysis will be presented at the meeting.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-36.
Abstract P2-10-37: Long-term prognosis of early breast cancer in a population-based cohort with a known BRCA1/2 mutation status.
Authors: Nilsson MP , Werner Hartman L , Idvall I , Kristoffersson U , Olsson H , Johansson O , Borg Å , Loman N 
Published: August 2014

Abstract
Background: The impact of germline BRCA1/2 mutations on breast cancer prognosis and treatment is currently not clear. We investigate how different factors, including BRCA1/2 mutation status, correlate with long-term outcome in early breast cancer in a population-based cohort.
Methods: As previously reported, all women in the Southern Health Care Region in Sweden with breast cancer diagnosed before age 41 years between 1990 and 1995 (n = 262) were contacted in 1996 and offered mutation analysis of the BRCA1 and BRCA2 genes. Mutation analysis was performed on 234 of them, the others were excluded from further studies. 23 pathogenic mutations were found; 18 in BRCA1 and 5 in BRCA2. We will now present data on tumor and patient characteristics, treatment and long-term follow-up for the patients from this population-based cohort. Three patients have declined further study follow-up and were therefore excluded. Six patients had metastatic breast cancer at the time diagnosis (one of them a BRCA2 mutation carrier) and are also excluded, leaving 225 in the present analysis.
Results: Among the 225 cases estrogen receptor (ER) status is known for 191 (49% ER+, 51% ER−); histologic grade for 169 (24% grade I; 33% grade II; 43% grade III); stage for 225 (36% stage I, 44% stage II, 20% stage III); type of surgery, adjuvant systemic treatment and postoperative radiotherapy for 225. In the cohort, 46% received adjuvant or neoadjuvant chemotherapy, whereas 15% were given adjuvant endocrine therapy. There is complete follow-up &gt; 10 years for 205 and present vital status for 224.
Of the 225 women, 128 (57%) have had a local, regional or distant recurrence of breast cancer (contralateral breast cancer not included) at the date of last follow-up. One hundred and six patients (47%) have died, 98 of whom from breast cancer and 2 from presumably radiation-induced malignancies caused by postoperative radiotherapy. Thirteen of the 22 BRCA1/2 mutation carriers (59 %) have died, all from breast cancer. Of the 9 mutation carriers that are alive today, 3 have had an in-breast tumor recurrence and 3 have had a contralateral breast cancer; the 3 women that have had neither have all performed bilateral prophylactic mastectomy as well as prophylactic salpingo-ooforectomy.
Data on how the long-term prognosis of early breast cancer is correlated to BRCA1/2 mutation status, adjuvant treatment, stage at diagnosis, histologic grade and ER status of the tumor will be presented.
Conclusion: Women with early breast cancer in this cohort from the early 90ies had a poor long-term prognosis. The prognosis for women diagnosed with early breast cancer today is likely to be better, thanks to more modern chemotherapy regimens, endocrine and targeted treatments. The prognostic significance of BRCA1/2 mutation status will be further analyzed.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-37.
Abstract P2-10-41: The prediction of invasion in ductal carcinoma in situ: developing prediction model and validation
Authors: Lee SK , Kim M , Nam SJ , Lee JE , Yang J-H 
Published: August 2014

Abstract
Background: The aim of the study was to determine factors and develop the model that predict the risk of invasion in patients with ductal carcinoma in situ (DCIS) diagnosed by preoperative biopsy.
Methods: We selected 497 patients underwent surgical treatment for preoperatively diagnosed DCIS of the breast between 1997 and 2009. Multivariate analysis was used to identify relevant clinical, radiological and pathological factors that may predict upstaging. A prediction model was developed based on significant factors and measured using the area under the receiver operating characteristics (ROC) curve. This prediction model was subsequently validated using the dataset of 149 cases who were diagnosed with DCIS preoperatively between 2010 and 2012.
Results: Of 24.75%, there was an upstaging to the invasive cancer. We found that larger size (≥1.5cm) of DCIS was most significant factor, followed by palpable lesion on physical examination, no expression of estrogen receptor (ER)/progesterone receptor (PR), high nuclear grade, non-cribriform subtype and absence of necrosis significantly associated with presence of invasion.

The prediction model with these factors showed that excellent predictive accuracy (the area under the ROC curve= 0.851, 95% CI: 0.817–0.881) and showed similar findings in the validation data set (AUC = 0.868, 95% CI: 0.800–0.916). After ranking the significant factors, we selected 4 factors to simplify the model. This simple model also showed good prediction power (AUC = 0.821, 98% CI: 0.784–0.854).

Conclusion: We developed the prediction model to predict upstaging in patients diagnose with DCIS preoperatively based on 4 most significant factors. By this prediction model, we suggest the axilla exploration with SLNB in case of DCIS with more than 1.5 cm size, palpable lesion, no expression of HR and high NG to avoid 2nd operation.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-41.