bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1-08-24: Clinical and Pathologic Characteristics of Diabetic Breast Cancer Patients in a Tertiary Care Safety Net Hospital.
Authors: Loch MM , Eapen A , Ross AA , Rosenberg C , Blanchard RA 
Published: June 2012

Abstract
Background: Recent studies have indicated an increased risk of breast cancer in women with diabetes, and an increase in disease specific mortality in patients with diabetes and breast cancer. Clinical and pathologic features of diabetic women with breast cancer have not been described. We examine tumor characteristics in diabetic women in our ethnically diverse tertiary care hospital that may help explain the increased mortality seen in diabetic women diagnosed with breast cancer.
Methods: We expanded a pre-existing database to include all women diagnosed with breast cancer from 1998–2011. From the electronic medical record we documented age, body mass index (BMI), place of birth, self-identified race/ethnicity, date of diagnosis, T, N, M stage, grade, ER, PR, HER2 expression, presence of diabetes (DM) or thyroid disease at diagnosis, recurrence and treatment data including neoadjuvant, surgical, adjuvant and radiation therapy and adequacy of treatment. We determined associations using contingency tables and multivariate logistic regression.
Results: 480 cases were identified. Patients were racially diverse: 35% white [W], 41% black [B], 14% Hispanic and 10% other. 23% had DM, 47% were obese (body mass index [BMI] &gt;30). Age in DM vs. non-DM were 63.327 vs. 57.729 (p= &lt; 0.0001) and BMI in DM vs. non-DM were 32.749 vs. 29.433 (p&lt;0.001). When exploring odds ratios (OR) of different tumor subtypes, none were statistically significant when controlling for age and BMI. The OR calculated were as follows: Triple negative 1.00 (confidence interval [CI]: 0.6−1.666, p = 0.9996), ER+ 1.063 (CI: 0.68−1.662, p=0.7877), PR+ 1.005 (CI: 0.67−1.506, p=0.9811), HER2+ 1.011 (CI: 0.578−1.768, p= 0.8535), recurrence: 1.090 (CI: 0.634−1.873, p= 0.7558). There were no significant interactions with DM and T, N stage when controlling for age and BMI. T stage: p=0.6962, N stage: p=0.7349 and recurrence p=0.5469 on recurrence controlling for age, BMI and grade: p=0.5462. There was no significant association between grade in DM vs. no DM with rates of grade in DM as follows: grade 1: 10.81%, grade 2: 49.55%, grade 3: 39.64% and in non-DM grade 1: 13.55%, grade 2: 45.8% and grade 3: 40.65%. Mean score difference p=0.7588. Conclusions: We did not find significant differences in our DM women compared with non-DM women when evaluating tumor subtype, T stage, N stage, grade or recurrence. In our patient population these factors do not play a role in the increased cause specific mortality in DM patients with breast cancer. Other factors must play a role in this and should be explored further.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-24.
P1-09-05: A 3′UTR Functional Variant in BRCA1: A Predictor of Poor Outcome in Breast Cancer.
Authors: Dorairaj JJ , Miller N , Newell J , Kerin MJ , Weidhaas JB 
Published: June 2012

Abstract
Background: MicroRNAs (miRNAs) are class of gene regulators which exert their effects through binding with partial complementarity to sequences in the 3'untranslated region (3'UTR) of the target mRNA. Single nucleotide polymorphisms (SNPs) in the 3'UTR of target mRNA have the potential to disrupt or create new illegitimate miRNA targets and have been associated with cancer predisposition as well as tumor biology. An association between rs8176318 and risk for familial breast and ovarian cancer as well as risk for triple negative breast cancer in African American women has previously been established. We aimed to evaluate the phenotypic effect of rs8176318 in a west of Ireland breast cancer cohort, and also its role as a biomarker of prognosis.
Methods: DNA from 727 unselected breast cancer cases and 387 controls were extracted from whole blood and genotyped for rs8176318 in the 3'UTR of the BRCA1 oncogene. The association with disease specific parameters and outcome were evaluated.
Results: Overall, there was a significant difference in the distribution of the three genotypes between cases and controls (p=0.035). The dominant variant model was predictive of breast cancer (OR=1.4, 95% CI 1.1−1.8). Fifty-two percent of breast cancer cases had the variant, with similar prevalence between subtypes: Luminal A (279 [54%] of 519 cases), Luminal B (37 [43%] of 85 cases), HER2 (21 [53%] of 40 cases) and triple negative breast cancer (41 [49%] of 83 cases). Comparing the prevalence of the variant within respective subtypes with controls however, Luminal A breast cancer was most strongly associated with rs8176318 (OR=1.5, 95%CI 1.1−1.9). The variant was not significantly associated with disease free survival (DFS) in all cancer cases (Log-rank test=0.084). However, rs8176318 was predictive of a poorer DFS (Log-rank test=0.041) in Luminal A patients with a 10-year DFS of 54% (95% CI 0.4−0.7) and 77% (95%CI 0.7−0.9) for the variant versus the non-variant, respectively. In addition, patients with Stage IV disease had a 6-fold increased risk of carrying the variant (p = 0.035), with 17 (73%) of 23 patients with metastasis at presentation positive for the variant compared to 324 (50%) of 642 patients without metastasis (p=0.034). Luminal A patients with Stage IV disease had a 13-fold risk of carrying the variant (p=0.043) in regression analysis, controlling for all other clinicopathological variables. Similarly, the variant was associated with distant metastasis in Luminal A patients, with 11 (92%) of 12 patients with metastasis positive for the variant compared to 242 (52%) of 463 patients without metastasis (p=0.028).
Conclusion: These findings suggest that rs8176318, a variant in the 3'UTR of BRCA1, is a genetic marker for modest breast cancer risk but aggressive tumor biology in breast cancer, and highlights the need for further clinical and biological evaluation of such markers.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-09-05.
P1-09-08: Association of Hypoxia-Inducible Factor-1 with Breast Cancer Risk: A Meta-Analysis of Published Studies.
Authors: Yin W , Liu G , Lu J , Shen Z , Shao Z 
Published: June 2012

Abstract
Background: Hypoxia-inducible factor-1 (HIF-1) plays an important role in the development and progression of breast cancer. However, conflicting results have been yielded for the association between HIF-1 polymorphisms and breast cancer risk. Therefore, we carried out a meta-analysis to assess the association of HIF-1 1772 C/T and 1790 G/A polymorphisms with breast cancer.
Material and methods: Computerized and manual searches were performed to identify eligible studies comparing allelic and genotypic frequency between cases and controls in breast cancer. Odds ratios (ORs) were used to estimate the association between HIF-1 polymorphisms and breast cancer risk. The fixed-effects or random-effects model was used to combine data. Subgroup analyses by ethnicity were also performed.
Results: This meta-analysis for 1772 C/T polymorphism included 1934 breast cancer cases and 1848 controls, and for 1790 G/A polymorphism included 602 breast cancer cases and 479 controls. We found that 1772C/T polymorphism increased the risk of breast cancer in the recessive model (OR = 2.273, 95% CI: 1.061−4.872, P = 0.035), whereas similar effect failed to be observed in the dominant model (OR = 1.075, 95% CI: 0.717−1.613, P = 0.725). There was a significant increase in breast cancer risk among Asian women (OR = 4.162, 95% CI: 1.508−11.484, P = 0.006) but not Turkish patients in the recessive model. For the 1790G/A polymorphism, we found that it had no exact effect on the decreased risk of breast cancer in both recessive and dominant model.
Discussion: This meta-analysis indicates that the polymorphism of HIF-1 1772C/T rather than 1790G/A polymorphism might be one of the high risk factors for breast cancer. The effect of the 1772C/T polymorphism on breast cancer risk is completely generated by the Asian women.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-09-08.
P1-11-04: Breast Cancer Treatment Resources and Guideline-Concordant Treatment in Appalachia.
Authors: Yao N , Hillemeier MM , Anderson RT , Matthews SA 
Published: June 2012

Abstract
Background: Appalachia has poorer cancer outcomes, but little research has been done regarding availability of cancer care resources in this region and how resource availability may relate to cancer outcomes. This study 1) examines associations between radiation therapy resources and receipt of radiotherapy after BCS in counties within Kentucky — a SEER state; and 2) describes spatial patterning of breast cancer treatment resources in all 13 Appalachian states.
Methods: For the Kentucky analyses, county-level data from the Area Resource File and SEER registry are analyzed. Bivariate analyses and spatial lag regression using a 6-nearest neighboring counties matrix are conducted. The sample includes stage I or II primary breast cancer patients age 18+ years diagnosed in Kentucky during 2000–2007. The dependent variable is the county-level percentage of patients received BCS without radiation; independent variables include density of radiation therapy providers and facilities and other socioeconomic covariates. For the analyses of entire Appalachian region, descriptive analyses and exploratory spatial data analysis are conducted including 420 Appalachian counties and 644 non-Appalachian counties in 13 states.
Results: In Kentucky 16.44% of 17,227 early stage breast cancer patients received BCS without radiation therapy (21.08% in Appalachia versus 14.80% in non-Appalachia, p&lt;0.001). Appalachian Kentucky had significantly fewer radiation oncologists and radiation therapy facilities per capita than non-Appalachian Kentucky. The number of radiation therapy facilities per capita is negatively associated with rates of BCS without radiation when controlling for covariates. Analysis of 13 Appalachian states shows that Appalachian counties, especially in the Central and Southern regions, had significant fewer physicians per capita in Surgery, Anesthesia, Clinical Pathology, and Radiation Oncology. Clustering of scarce breast cancer care resources was observed in Central Appalachia.
Conclusions: Appalachian counties, especially in central Appalachia, have fewer breast cancer treatment resources than non-Appalachian counties, and resource availability is associated with cancer health disparities.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-04.
P1-11-12: Patterns of Care of Newly Diagnosed Patients with Breast Cancer in Mexico.
Authors: Chavarri-Guerra Y , Liedke PER , Symecko H , Hammond EE , Higgins MJ , Finkelstein D , Goss PE 
Published: June 2012

Abstract
Background: Breast cancer is the most common form of cancer and the leading cause of cancer death in women worldwide. More than 55% of breast cancer deaths occur in low and middle income countries. Although incidence rates for breast cancer are lower in developing countries, mortality rates are higher. This phenomenon has been attributed to limited access to care for breast cancer patients, including screening and early diagnosis as well as primary surgical, radiation and systemic therapies. Similar to trends in other poor and middle income countries, breast cancer mortality in Mexico is rising. The goal of this survey of physicians caring for patients with breast cancer in Mexico is to obtain information about current treatment patterns of newly diagnosed patients and to describe their clinical characteristics. Methods: A web-based closed survey has been sent to 854 physicians providing care to newly diagnosed breast cancer patients across Mexico, including medical oncologists and breast cancer surgeons. The survey instrument contains 35 questions assessing demographic data, access to diagnosis and treatment in a variety of clinical patient scenarios. The responses will be anonymous and entered automatically into a secure database for analysis. Fisher exact test will be used for the frequency analysis. Chi-squared statistics and Kendall correlation will be used for nominal and ordinal variables respectively. Results: The results will be presented at the 2011 San Antonio Breast Cancer Symposium.
Conclusions: The results of this survey will highlight potential disparities in care received by breast cancer patients across the full geographic and socioeconomic spectrum of Mexico in order to highlight the need for uniform, quality based approaches for the diagnosis and treatment of breast cancer patients in Mexico, and will serve as an example of how one middle income country faces challenges and unmet medical needs regarding access to care of women with breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-12.
P1-12-23: HER4 Coexpression Is Associated with Improved Recurrence Free Survival in HER2−Positive, Herceptin Treated Patients.
Authors: Brockhoff G , Machleidt A , Piendl G , Seegers S , Sassen A , Diermeier-Daucher S , Buchholz S , Ortmann O 
Published: June 2012

Abstract
Background: Individual therapy efficiency of HER2−positive metastatic and pre-metastatic breast cancer patients varies significantly and spans from effectual responsiveness over acquired insensitivity to complete resistance from the outset. Thus no predictive information can be deduced from HER2 diagnostics so that molecular biomarkers indicative for sensitivity / resistance to Herceptin are needed to be identified. The HER2 related HER4-receptor has been shown to have ambivalent (pro-apoptotic or pro-proliferative) activity and consequently represents a prime candidate to affect HER2 activity under Herceptin treatment. We retrospectively analyzed potential her4 gene amplification and HER4 protein expression in HER2−positive, Herceptin treated patients. Patient's overall and recurrence free survival was evaluated as a function of HER2/HER4 expression. Methods: Using dual color Fluorescence in-situ Hybridization (FISH probes, Zytovision, Bremerhaven, Germany) and qPCR (LC480, Roche, Penzberg, Germany) we quantitatively investigated primary breast cancer tissues from nearly 50 (FISH) and 160 (PCR) patients who received Herceptin treatment. We quantified the her4 gene copy numbers and evaluated the protein expression profile of all four known HER4 isotypes (JM-a/CYT1, JM-a/CYT2, JM-b/CYT1, JM-b/CYT2). Results: FISH analysis revealed a positive and independent prognostic marker in Herceptin treated breast cancer patients with respect to overall survival. Moreover by quantitative PCR analysis we found a significant variability of HER4 protein expression (JM-a/CYT1 and JM-a/CYT2; no JM-b isotypes) in HER2 positive breast cancer tissues, whereas HER2/HER4 positive patients show a significant better recurrence free survival compared to HER2 positive but HER4 negative patients (p = 0,003).
Conclusions: HER4 has been demonstrated to potentially exert tumor suppressing activity and in turn to have a favourable impact on the course of breast cancer disease. We show here that HER4 expression prolongs in particular recurrence free survival of Herceptin treated patients which indicates a functional integration of HER4 into anti-HER2 targeting. Complementing functional studies allowing for isotype specific function of HER4 will elucidate the special role of this receptor tyrosine kinase in the context of Herceptin treatment and might facilitate individualized anti-ErbB-receptor targeting with higher efficiency.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-23.
P2-01-10: Blockage of Autocrine TGF-b Signaling Reduces Tumorigenecity and Lung Metastasis in a Murine Breast Cancer Cell Line, NMuMG-ST.
Authors: Liu Z , Robert NW , Wang L , Bandyopadhyay A , Sun L-Z 
Published: June 2012

Abstract
Transforming growth factor beta (TGF-b) is known to have a dualistic role in breast cancer cells, acting as a tumor suppressor or a tumor promoter. This dualistic property varies in different cells and at different progression stages. Studies show that autocrine TGF-b is necessary for the growth and survival of MDA-MB-231 cells, and was also known to enhance the survival of MCF-7 cells. However, the role of autocrine TGF-b in spontaneously transformed cells is still less understood. We have retrovirally transduced a dominant negative TGF-b Type II receptor (DN RII) into a spontaneously transformed murine mammary gland epithelial cell line NMuMG-ST (DN RII cells). The expression of DN RII reduces TGF-b sensitivity of NMuMG-ST cells in a gene transcription assay and a growth inhibition assay. Interestingly, the autocrine TGF-b supports the survival of NMuMG-ST cells, although the exogenous TGF-b inhibits the growth of NMuMG-ST cells. Moreover, more apoptosis were observed in the DN RII cells compared to the control cells in both in vivo and in vitro experiment. We found that AKT and ERK pathway mediates autocrine TGF-b's survival signal. Results of western immunoblot for several stem cell markers and mammosphere formation assay suggest that autocrine TGF-b signaling is essential for the maintenance of stem like cell subpopulation in NMuMG-ST cells. By using immunocytostaining, we found that the DN RII cells expressed more E-cadherin and less Vimentin when compared to the control NMuMG-ST cells, which indicate that blocking autocrine TGF-b signaling pathway could inhibit the process of EMT in NMuMG-ST cells. Notably, when the cells were inoculated orthotopically in nude mouse mammary glands, tumors formed by DN RII cells grew at a similar rate as those formed by control cells, but caused fewer lung metastases. Our finding identified that the autocrine TGF-b signaling is important for the survival and metastatic ability of NMuMG-ST, which could provide an important foundation for further investigation on the role of autocrine TGF-b signaling in breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-10.
P2-01-24: Triple-Negative Breast Cancer Emerges from the Luminal Progenitor Compartment.
Authors: Nogi H , Kamio M , Kato K , Kawaase K , Toriumi Y , Takeyama H , Uchida K 
Published: June 2012

Abstract
Background: Triple-negative breast cancers (TNBC) are defined as tumors that lack expression of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type 2 (HER2). Majority of TNBC (approximately 80%) are basal-like breast cancers. The question of whether there is a specific, identifiable cell in the normal breast form which basal-like breast cancers arise is controversial. We evaluated the frequency and receptor status of ductal carcinoma in situ (DCIS) and ductal components associated with T1 invasive ductal carcinoma (IDC) to clarify the developmental pathway of TNBC.
Methods: From our institutional archives between April 2000 and April 2011, we retrieved 758 cases of DCIS and T1 invasive ductal carcinoma without prior operative treatment. Immunohistochemistry for ER, PgR and HER2 was performed on ductal components and invasive components. Statistical analysis was performed using Fisher Extract Test.
Results: The frequencies of triple-negative (TN) subtype at each size were not seen significant differences. Ductal components were seen in 51 (84%) TN-IDC cases. Within 51 cases, the ductal components were TN in 49 cases. The remaining 3 cases were positive for ER and PgR, but negative HER2.

Conclusion: The resemblance between ductal components and invasive components and the coincident frequency of TNBC at each size sustain the hypothesis that TNBC arise from the luminal progenitor compartment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-24.
P2-02-03: MAP3K3, Amplified in Human Breast Cancer, Promotes Breast Tumor Progression and Defines Poor Prognosis.
Authors: Dong J 
Published: June 2012

Abstract
Gene amplification in the 17q chromosomal region is observed frequently in breast cancers. An integrative bioinformatics analysis nominated MAP3K3 gene, located in 17q23, as a potential therapeutic target in breast cancer. This gene encodes the mitogen-activated protein kinase kinase kinase 3 (MEKK3), but has not yet been associated with cancer-causal genetic aberrations. We found that MAP3K3 was amplified in approximately 8–20% of breast carcinomas, and that its over-expression was an independent prognostic marker for poor outcome with respect to relapse-free and overall survival, especially among the estrogen receptor-positive breast cancer patients. shRNA-mediated knockdown of MAP3K3 expression significantly inhibited cell proliferation and colony formation of MAP3K3-amplified breast cancer cell lines MCF7 and MDA-MB361, and promoted breast cancer cell apoptosis induced by TNFα, TRAIL, or a doxorubicin. In addition, ectopic expression of MAP3K3, in collaboration with Ras, induced colony formation in both primary mouse embryonic fibroblasts and immortalized mammary epithelial cells (MCF-10A). Together, these results suggest that MAP3K3 is a potential biomarker indicating poor prognosis, contributes to resistance to therapy, and is an oncogene in breast carcinogenesis. Therefore, therapeutic targeting of MAP3K3 may be attractive in breast cancer patients with MAP3K3-amplified breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-02-03.
P2-02-04: Novel Functions of vps34 in Non-Transformed Epithelial Cells: Regulation of Cell Proliferation and Tumorigenesis.
Authors: Su H , Xu T , Ganapathy S , Yuan Z-M 
Published: June 2012

Abstract
Autophagic and endocytic pathways are tightly regulated membrane rearrangement processes that are crucial for homeostasis, development and disease. A list of proteins regulating these cellular processes show altered expression in cancers, suggesting derailed autophagy or endocytosis as an emerging feature of cancer. Class III phosphatidylinositol 3-kinase (PI3kinase) Vps34 regulates both autophagic and endocytic systems by recruiting proteins containing PtdIns3P binding domains. Recently, many new insights into the biology of class III PI3Kinase have been reported. Most of these studies, however, used mainly transformed cells. It is unclear whether class III PI3Kinase works similarly in non-transformed cells. In the recent study, we explored this by depleting both transformed and non-transformed mammary epithelial cell lines of Vps34 using shRNA. In consistent with previous finding, vps34-depleted cells are defect in formation of FYVE-GFP puncta, and showed altered early and recycling endosome dynamics. In a shark contrast to transformed cells where knockdown of Vps34 was associated with decreased growth, Vps34 deficiency in non-transformed cells resulted in a marked increase in cell proliferation. The deregulated autophagy function found in Vps34-depleted cells appeared to be not involved in cell growth regulation as silence of either Atg7 or Beclin1 expression did not affect the growth rate. On the other hand, reporter luciferase-based ten-pathway screens suggested an altered activity of the MAPK pathway. Indeed, biochemical analysis indicated a sustained ERK activation resulting from the impediment of endosome-mediated EGFR turnover in Vps34 deficient cells. A contribution of the endosomal pathway to Vps34-mediated regulation of cell proliferation was further confirmed by using Rab5 and Rab11 mutants that deregulated early and recycling endosome, respectively. Importantly, inactivation of Vps34 compromised the cellular barrier against oncogene-mediated transformation, as demonstrated by the increased susceptibility of Vps34 depleted cells to Ras-induced colony formation in vitro and tumor development in mice. All together, our data uncover a novel role for the class III PI3Kinase-endosomal pathway in regulation of cell proliferation.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-02-04.