bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-09-15: Polymorphism of the CYP2D6 gene in Brazilian women with breast cancer treated with tamoxifen
Authors: da Silva BB , de Vasconcelos-Valença RJ , Lopes-Costa PV , Gebrim LH 
Published: August 2014

Abstract
The prodrug tamoxifen is the standard endocrine treatment for estrogen receptor-positive breast cancer. Its effect depends on activation by the CYP2D6 enzyme, which is encoded by a highly polymorphic gene that varies according to ethnicity. The most important polymorphic variants are *4 (abolished enzyme activity), *10 and *17 (decreased enzyme activity) found in 25%, 38-70% and 35% of Caucasians, Asians and Africans, respectively, resulting in low endoxifen levels (a major metabolite), a lack of response to tamoxifen and a poor prognosis. There is a widespread racial miscegenation in Brazil and the country's public health care system has made tamoxifen available and free of charge to all women with hormone-sensitive breast tumor despite the undetermined genetic profile of these patients.This study aims to evaluate polymorphism frequency of the CYP2D6*4, *10 and *17 alleles in Brazilian breast cancer patients under tamoxifen treatment and metabolism phenotype. Methods: The study was approved by the Internal Review Board of the Federal University of Piauí. All patients signed an informed consent term before study entry. Sixty-five women with estrogen and progesterone receptor-positive and Her-2 negative breast carcinomas were enrolled in the study. A 3-ml peripheral blood sample was collected from each patient, using specific polymerase chain reaction technique (PCR) to analyze haplotypes *1, *4, *10 and *17, determined by studies of different Single-Nucleotide Polymorphism (SNP). Microsoft Office Excel software 2010 was used to compile and analyze the data obtained. Results: The frequency of CYP2D6 alleles *4, *10 and *17 was 17%, 37% and 3%, respectively. Haplotype *1/*10 was present in 26%, while the phenotype of intermediate metabolism occurred in 12% of the women studied. Conclusion: The present study showed a polymorphism frequency of CYP2D6, mainly of allele *10 and a deficiency in tamoxifen metabolism, characterized by intermediate metabolism in 12% of the women studied. Nevertheless, further studies must be developed with a larger sample of women to study not only the presence of the polymorphic variant but also disease prognosis.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-09-15.
Abstract P5-11-01: Impact of CDK mediated Smad3 phosphorylation and Pin1 in triple negative breast cancer cell migration
Authors: Hamdan R , Jeruss JS 
Published: August 2014

Abstract
Introduction: Estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancers, also known as triple negative breast cancers can overexpress cyclins, such as cyclin D and E, which have been linked to cancer progression and metastasis. Cyclin/CDK complexes can phosphorylate and regulate Smads, downstream signaling proteins in the transforming growth factor-beta (TGF-b) superfamily. CDKs phosphorylate Smad3, predominantly in the linker region, resulting in the decreased tumor suppressive role of this protein. The peptidyl-prolyl cis/trans isomerase Pin1 is also overexpressed in breast cancer. Pin1 can bind phosphorylated Smads contributing to TGF-β induced cell migration and invasion. Inhibition of CDK-mediated Smad3 phosphorylation has been shown to restore Smad3 activity and decrease tumor cell migration in vitro. Based on these findings, we hypothesized that inhibition of Pin1 or CDK-mediated Smad3 phosphorylation would result in decreased triple negative breast cancer cell migration.
Methods: Hs578T, MDA-MB-436, and MDA-MB-231 triple negative breast cancer cells (TN) were transfected with either an si control (siCN) or an siPin1 plasmid to knockdown Pin1 protein expression. Transwell migration assays were used to determine the effect of Pin1 knockdown on migration. TN cells were treated with CDK4 or CDK2 inhibitors alone or in combination. The study cells were also stably transduced with lentiviral empty vector, wild-type (WT) Smad3, or a Smad3 mutant (5M) resistant to CDK-mediated phosphorylation. The effect of pharmacologically or genetically inhibiting CDK-mediated Smad3 phosphorylation on Pin1 binding to phosphorylated Smad3 (p-Smad3) or total Smad3 was determined using a co-immunoprecipitation assay (Co-IP).
Results: Transfecting the study cells with siPin1 resulted in decreased cell migration when compared to the siCN transfected cells. Treatment with the CDK4 or CDK2 inhibitors alone or in combination did not affect Pin1 protein levels, but resulted in decreased Pin1 binding to p-Smad3 with the greatest decrease found after treatment with combination therapy. Similarly, transduction of the study cells with the WT or the 5M Smad3 constructs had no effect on Pin1 levels but resulted in decreased Pin1 binding to Smad3. The greatest decrease was observed in the 5M transduced cells.
Concusions: Inhibition of CDK-mediated Smad3 phosphorylation and knock down of Pin1 resulted in decreased migration of TN breast cancer cells. Inhibition of CDK-mediated Smad3 phosphorylation by mutation of the CDK phosphorylation sites or by treatment with CDK4 and CDK2 inhibitors negatively impacted Pin1 binding to Smad3. Together, these findings indicate that CDK-mediated Smad3 phosphorylation enhances Pin1 binding to Smad3 and promotes tumor cell migration in triple negative breast cancer cells.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-11-01.
Abstract P5-11-02: Radiation instigates EMT, CSC self renewal and pluripotency signal transduction in non-targeted (bystander) ERa+ and triple-negative breast cancer cells
Authors: Khan FH , Natarajan M , Aravindan S , Herman TS , Aravindan N 
Published: August 2014

Abstract
Ascertaining radiation-induced bystander response in non-targeted tumor cells, particularly on variables pertaining to resistance, relapse and tumor progression, may escort significant clinical implications. Accordingly, in this study, we investigated the radiation induced alterations in factors that drive the epithelial-to-mesenchymal transition (EMT), cancer stem cells (CSCs) self-renewal capacity and pluripotency maintenance in non-targeted breast (ERa+ MCF-7 and triple-negative MDA-MB-468) adenocarcinoma cells. Co-cultures of non-targeted breast cancer cells with irradiated (5Gy) counterparts for 24h were assessed for transcriptional regulation of 93 stem cell related molecules using QPCR profiling. Radiation-induced alterations in the expression of ABCG2, E-Cadherin, N-Cadherin, MYC, Nanog and SOX2 in bystander MCF-7 and MDA-MB-468 were assessed using western blot analysis. Radiation profoundly increased the transcriptional activation of stem-cell related molecules in distant bystander ERα+ MCF-7 (70 genes) and in triple-negative MDA-MB-468 (82 genes) cells. Interestingly, 62 of 70 genes activated in MCF-7 and 81 of 82 genes in MDA-MB-468 showed significant (&gt;2 fold) upregulation. Evidently, radiation induced 66 genes (&gt;2 fold, 58 genes) in bystander breast cancer cells independent of their hormone status. Consistently, immunoblotting revealed increase in the expression of ABCG2, N-Cadherin, MYC, Nanog and SOX2 in both MCF7 and MDA-MB-468. Together, these data demonstrates that radiation activates the EMT, CSCs self-renewal and pluripotency maintaining factors in non-targeted bystander cells and could thus play an instrumental role in breast cancer relapse and progression.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-11-02.
Abstract P5-11-03: Deciphering the role of HER3-DJ-1 interaction in breast cancer
Authors: Mukherjee S , Huang Z , Fa M , Dhupkar P , Mujoo K , Zhang N , An Z 
Published: August 2014

Abstract
Advanced breast cancer is notorious for its aggressive nature and poor prognosis. An ablated regulation in the EGFR family receptor signaling has been linked to the development of numerous tumor types, including breast cancer. HER3 is a unique member of the EGFR family that lacks intrinsic tyrosine kinase activity. However, HER3 can initiate signaling when dimerized with other family members such as HER2. HER3 overexpression is correlated with poor survival in breast cancer patients. HER3 also plays an important role in drug resistance mechanism such as in trastuzumab resistant breast cancer cell lines where it dimerize with EGFR to initiate signaling via the PI3K/Akt pathway. The identification of interaction partners of HER3's C-tail is critical to understand the signaling mechanism underpinning HER3's role in drug resistance and in progression of breast cancer. Our laboratory has identified a panel of novel HER3-interacting proteins by a combined immunoprecipitation and mass-spectrometry approach. One of the novel HER3 interacting proteins is DJ-1 which is a chaperone protein that plays an important role in the development of many cancers, including breast cancer. DJ-1 knockdown in high HER3 expressing breast cancer cell lines such as MCF-7 and MDA- MB-453 resulted in the reduction in HER3 levels as well as proteins downstream of the HER3 signaling pathway such as MAPK. We have also demonstrated that DJ-1 knockdown led to decrease in cancer cell proliferation. Studies are now in progress to determine the mechanism of regulation of HER3 by DJ-1 and the impact of DJ-1 KD in in vivo breast cancer xenograft models. These studies will help us to decipher key molecules which regulate HER3 mediated signaling and their role in breast cancer development and progression.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-11-03.
Abstract P5-11-08: SRA/SRAP contributes to TGF-b1 induced cell motility in cancer cells
Authors: Cooper CM , Yan Y , Xu W , Tsuyuki D , Hamedani MK , Davie JR , Leygue E 
Published: August 2014

Abstract
The steroid receptor RNA activator gene (SRA1) is a particularly intriguing genetic system in that both the corresponding RNA (SRA) and protein (SRAP) have been proven to be functional. Accumulated evidence overall suggests that both molecules act as distinct co-regulators of transcription, housed in ribonucleo-protein complexes able to positively or negatively regulate the activity of multiple transcription factors including -but not limited to- several nuclear receptors, MyoD and DAX-1.
A role for SRA/SRAP deregulation during breast tumorigenesis has been suggested. Indeed, not only do these molecules regulate the activity of both Estrogen Receptors, these major players in breast cancer etiology, but it has also been shown that SRA RNA is more highly expressed in breast tumors than in normal tissue, and that high levels of SRAP correlated to poorer survival in specific subsets of breast cancer patients.
In order to identify the genes and pathways regulated by SRA/SRAP, we performed deep sequencing of transcriptomes from MDA-MB-231 cells depleted of these molecules following RNA interference. The expression of 149 genes was consistently and significantly altered in four independent experiments comparing control RNAi vs SRA RNAi. Interestingly, cluster analysis using Ingenuity software defined a subset of genes (23 out of 149) directly associated with cell movement. Among them figured TGFBR1 (ALK5), a cell surface receptor-kinase mediating TGF-b signalling and a known promoter of cell motility in breast cancer cells.
We have now confirmed by quantitative PCR analysis a 40% decrease, upon SRA/SRAP depletion, of TGFBR1 mRNA expression in MDA-MB-231 cells as well as in other breast (MCF7, T5) and non-breast (Hela) cancer cell lines. Consistent with this decrease a drop to 60% of the basal TGFBR1 protein expression is seen by Western blot when MDA-MB-231 cells are depleted of SRA/SRAP. Western blot analyses also revealed that phosphorylation of several SMAD molecules, downstream effectors of TGFBR1 activation by TGF-β1, is impaired in the absence of SRA/SRAP in both MDA-MB-231 and Hela cells. This suggests that SRA/SRAP could potentially regulate TGF beta induced cell motility.
Using migration cell assays, we have now confirmed that upon TGF-β1 treatment for 6 hours, SRA/SRAP depleted cells had a significant decrease in migration as compared to control cells. Accordingly, live cell migration assays generated by a time-lapse videomicroscopy system, showed an increased track length and speed in both Hela and 231 cells over-expressed SRAP upon 10 h TGF-β1 treatment.
Taken together, these data suggest a cross-talk between SRA/SRAP and TGF-β signalling and induced cell motility.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-11-08.
Abstract P5-12-01: A comparison of hormone receptor status in black women born in the U.S., West Africa, East Africa and the Caribbean - A SEER analysis
Authors: Haynes BM , Ruterbusch JJ , Simon MA , Cote ML 
Published: August 2014

Abstract
Background: Breast cancer is the leading cancer diagnosed among women in the United States (U.S.) and is second only to lung for cancer-related deaths in women. Although white women have a higher incidence of breast cancer, African American (AA) women with breast cancer have higher breast cancer related mortality and have a lower five year survival (73.8%) compared to their white counterparts (81.6%). AA women are also diagnosed at a younger age, with 30-40% of AA women diagnosed under 50, compared to 20% of whites, and are more likely to present with more estrogen receptor negative/progesterone receptor negative (ER-/PR-) tumors than whites (42% vs. 29% respectively). Other studies suggest these disparities extend to black African women and white European women. The aim of this study is to determine whether breast cancer characteristics seen in U.S. born black women are comparable to African born black women and to provide additional insight on the role of race and genetic ancestry in breast cancer.
Methods: Surveillance, Epidemiology, and End Results (SEER) data (SEER 18 Registries) was used to examine hormone receptor (HR) status among 30,003 black women, born in the U.S. (28,838), West Africa (167), East Africa (183), or the Caribbean (815), diagnosed with a first primary breast cancer from 2000 through 2009. Chi-square tests were used to determine whether clinical variables differed by ethnic group. Proportional incidence ratios (PIR) and 95% confidences intervals (CI) were calculated to estimate excess risk of ER-/PR- tumors between the populations.
Results: There were no statistically significant differences in axillary lymph node, stage, histologic type, or surgical treatment at presentation by ethnic group. There was no statistically significant difference in the proportion of ER-/PR- receptor status comparing US blacks to black women born in West Africa (p-value = 0.16, PIR = 0.77, 95% CI: 0.56-1.05), however women from East Africa and the Caribbean were less likely to have ER-/PR- breast cancers compared with US born blacks. (PIR = 0.52, 95% CI: 0.35-0.74, p &lt; 0.0001 PIR = 0.84, 95% CI: 0.73-0.97, p&lt; 0.01 respectively). The crude overall 5-year survival rate of West African, East African and Caribbean born black women was significantly higher than those born in the U.S. (75.7%, p = 0.023, 85.9% p &lt;0.0001, 84.0% p&lt;0.0001, 65.3% respectively).
Discussion: Our results agree with historical data showing that many AA women have ancestral origins in West Africa and provides additional evidence supporting the role of ancestral genetics in breast cancer susceptability.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-12-01.
Abstract P5-12-03: Racial differences in breast cancer survival in a large urban integrated health system
Authors: Simon MS , Ruterbusch JJ , Pressler ME , Lamerato L , Krajenta R , Booza JC , Schwartz K 
Published: August 2014

Abstract
Background: Despite improvements in breast cancer outcomes, there continues to be a large gap in survival between African American (AA) and White women with breast cancer, which may be due at least in part to racial differences in access to care. In order to better understand breast cancer survival disparities, we evaluated factors that predict racial differences in survival among women treated at a large integrated health care system in Southeastern Michigan. Materials and Methods: The study population included 2,387 women (34% AA) with stage I through III breast cancer treated at the Henry Ford Health System (HFHS) from 1996 through 2005. Linked datasets from the HFHS, the Metropolitan Detroit Cancer Surveillance System (MDCSS) and the U.S. Census Bureau were used to obtain socio-demographic and clinical information. Co-morbidity was assessed by the Charlson co-morbidity index (CCI), and economic deprivation was categorized into 5 quintiles of increasingly worse socioeconomic deprivation, using a census tract deprivation index (DI). Results: AA women were significantly more likely than Whites to have larger (41% vs. 32% &gt; 2 cm) and hormone receptor (HR) negative tumors (30% vs 19%), to have a higher CCI (15% vs 9% &gt; 2) and to reside in a more economically deprived area (46% vs. 5% residing in quintile 5). Unadjusted analysis showed that AA had a significantly higher risk of death than White women (hazards ratio [HR], 1.36, 95% confidence interval [CI], 1.16-1.59). After multivariable adjustment for clinical (age, stage, HR and CCI), and societal factors (insurance, DI), race was no longer significantly associated with overall survival, HR, 1.12, 95% CI, 0.94-1.33, p = 0.22, and 1.02, 95% CI 0.83-1.24, p = 0.88, respectively. Stratified analyses by DI showed no racial difference in survival for each of 5 levels of DI. Discussion: In a large urban integrated health care system, racial differences in breast cancer survival appear to be related to clinical and socioeconomic characteristics.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-12-03.
Abstract P5-12-07: Triple-negative breast cancer in African American women - How women in New Orleans compare to the rest of Louisiana and the Nation
Authors: Loch M , Li X , Estrada J , Reske T , Chen V , Wu X-C 
Published: August 2014

Abstract
Background: For years clinicians have made the empirical observation that there is an unusually high number of African American women (AAW) with triple-negative (Tneg) breast cancer (BC) in New Orleans (NO). Knowing the rate of Tneg BC in AAW is higher than white women (WW), we explored the hypothesis that AAW in NO have a higher rate of Tneg BC when compared to AAW in the rest of Louisiana (LA) and the US.
Methods: We analyzed data from the Louisiana Tumor Registry, one of the NCI funded SEER registries, for the tumor characteristics of invasive female BC diagnosed in 2010, focusing on racial disparities; HER2 status was not available prior to 2010. We explored the association of HER2 status with age, race, ER, PR, T, N and M status to determine crude and adjusted odds ratios and rate distribution of subtypes using SEER*Stat and SAS programs. With the recent release of SEER 18 data including HER2 status in cases diagnosed in 2010 we also looked at national rates of Tneg BC in WW compared to AAW and compared these findings to NO and LA.
Results: Overall age-adjusted incidence rate of Tneg BC in AAW was 34.0 per 100,000 in NO, 27.2 per 100,000 in AAW in the rest of LA and 20.4 per 100,000 in SEER 18. This translates into a statistically significant increase in incidence rates of Tneg BC in AAW in NO by 67% (p = &lt; 0.05) compared to SEER 18. The rates in WW were 11.3 per 100,000 in all 3 locations. AAW with Tneg BC in NO were more likely to have more aggressive BC. Young age, black race, large tumor size, higher grade and TNM stage were significantly associated with the high risk of Tneg BC. After adjusting for age, geographic area, and other tumor characteristics, the higher risk of Tneg BC in AAW remained in NO compared with the rest of LA and locations of the SEER 18 registries.
Table 1: 2010 Tneg rates per 100,000 in NO, LA and SEER 18 RateCountRate RatioRate Lower CIRate Upper CIWhiteSEER 1811.33884154 LA11.30512000.99700.85731.1543 NO11.2441320.99160.66501.4340BlackSEER 1820.39961094 LA27.18622041.33271.13841.5534 NO34.0092611.66721.25822.1711
Conclusions: The incidence rates of Tneg BC in AAW in NO and LA are significantly higher than in SEER 18, with rates in NO being the highest. Rates of Tneg BC in WW in all data sets were similar. SEER 18 analysis also confirms a higher incidence of Tneg BC in AAW compared with WW as previously reported in smaller case series. AAW in NO are more likely to have poorly differentiated and Tneg BC compared to AAW in the rest of LA. This newly identified disparity in the AAW population in NO has clinical implications and translational research potential as it enables us to broaden the understanding and treatment of this aggressive disease.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-12-07.
Abstract P5-12-09: Clinical stage, not race, predicts receipt of sentinel lymph node biopsy in medically-underserved patients
Authors: Wiatrek RL , Kao LS , Robinson EK , Rieber AG , Ko TC , Wray CJ 
Published: August 2014

Abstract
Background: Sentinel lymph node biopsy (SLNB) has replaced axillary node dissection for staging clinically node negative breast cancer patients. Previously, other investigators have found disparities in the rate of SLNB in African Americans. Therefore, we hypothesized that African Americans and Hispanics are offered SLNB less frequently than Caucasians in a large safety-net hospital.
Methods: A retrospective review of female patients who underwent breast cancer surgery from 2002-2011 at a safety-net hospital was completed. Data was collected from the institutional cancer registry and medical record for: age at diagnosis, patient demographics, pathologic and clinical stage at presentation, and receipt of SLNB. Patients with clinically negative nodes (N0) were determined to be appropriate for SLNB. Patients with clinically positive nodes, biopsy proven nodal involvement, or stages IIIC or IV were deemed not appropriate for SLNB.
Results: Of 566 patients, the mean age at diagnosis was 53 years (range: 28-79); 46% (n = 269) were Hispanic, 31% African American (n = 174), 17% Caucasian (n = 95) and 5% Asian/Other (n = 28). Based on clinical stage, which was available for 561 patients, 64% were eligible for SLNB. Of those, 95% received appropriate SLNB. Race was not a predictor of eligibility for or receipt of appropriate SLNB.
TotalCaucasianAfrican AmericanHispanicOtherp-value %(n = 566)%(n = 95)%(n = 95)%(n = 269)%(n = 28) Clinical Stage 0.70010.4 (59)7.4 (7)10.9 (19)11.2 (30)10.7 (3) 123.5 (133)25.3 (24)24.7 (43)22.7 (61)17.9 (5) 2A28.3 (160)29.5 (28)24.7 (43)11.5 (31)35.7 (10) 2B15.4 (87)18.9 (18)19.0 (33)7.1 (19)17.9 (5) 3A6.0 (34)5.3 (5)5.7 (10)7.8 (21)0 3B7.6 (43)8.4 (8)6.9 (12)7.8 (21)7.1 (2) 3C3.4 (19)1.1 (1)1.7 (3)5.2 (14)3.6 (1) 44.6 (26)3.2 (3)5.7 (10)4.5 (12)3.6 (1) Unknown0.9 (5)1.1 (1)5.7 (10)0.7 (2)3.6 (1) Appropriate for SLNB64.0 (362)67.4 (64)61.5 (107)63.2 (170)75.0 (21)0.48Received appropriate SLNB94.7 (343)93.8 (60)92.5 (99)95.9 (163)100.0 (21)0.28
Conclusions: There was no difference in the rate of SLNB between racial and ethnic minority patients at a large safety-net hospital. The previously reported disparity likely resulted from more advanced presentation of disease rather than lack of appropriate care. Efforts to improve disparities seen in medically underserved patients should be focused on earlier detection and treatment of breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-12-09.