bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-06-01: Human mammary tumor virus, HMTV, is an MMTV-adapted human pathogen
Authors: Holland JF , Jaffer S , Melana S , Nartey T , Gnjatic S , Pogo BG-T 
Published: May 2016

Abstract
Forty percent of American women's breast cancers contain HMTV, a betaretrovirus 90-98% homologous to MMTV, the causative agent for breast cancer in mice. HMTV is reverse-transcribed and integrated into chromosomal DNA of human breast cells. MMTV contamination of our analyses has been definitively excluded. In 8% of unselected American mothers HMTV is found in cells in milk, but in 21% of milks from women previously biopsied for unconfirmed cancer suspicion. In breasts biopsied for suspicion of cancer before a later diagnosis of breast cancer, we see suggestive morphologic changes if the subsequent breast cancer is HMTV+. HMTV is infectious in vitro for B and T lymphocytes, dendritic cells, and human mammary epithelial cells. Infecting MCF-10 breast cell lines with HMTV produces molecular changes of epithelial-mesenchymal transition with upregulation of vimentin ,and downregualtion of E-cadherin. The excess of breast cancer in western European countries and their former colonies (age standardized rates of 47 to 92 per 100,000 per year) compared to Asian incidence (29 to 43 ASR/y) can be explained by excess HMTV-related breast cancer incidence. In 7 West European, American and Oceania countries, 30 to 60% contain HMTV, while in 5 Asian nations HMTV in breast cancers ranges from 0 to 22% Different indigenous murine species with disparate MMTV burdens parallel these findings: mus domesticus in the West with much MMTV in its genome, and m. castaneus or m.musculus in the East with less. Ancient contamination of the food chain, and current lactational transfer perpetuate infection. HMTV poses a new and challenging dimension to breast cancer research involving diagnosis, molecular mechanisms, epidemiology, therapy and prevention.
Citation Format: Holland JF, Jaffer S, Melana S, Nartey T, Gnjatic S, Pogo BG-T. Human mammary tumor virus, HMTV, is an MMTV-adapted human pathogen. [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 P4-06-01.
Abstract P4-07-06: Imipramine Blue - A safe and potent therapeutic regimen that suppresses breast cancer growth and progression by targeting DNA damage surveillance pathway
Authors: Rajamanickam S , Subbarayalu P , Timilsina S , Gorthi A , Drake MT , Chen Y , Vadlamudi R , Bishop AJR , Arbiser JL , Rao MK 
Published: May 2016

Abstract
Despite improvement in overall survival of breast cancer patients, many women don't survive this disease. Moreover, the quality of life for patients who do survive is often substantially reduced due to the toxicity associated with the chemotherapy. Here, we report that imipramine blue (IB), a novel analogue of anti-depressant imipramine that we recently synthesized, may serve as a safe and potent therapeutic agent for treating breast cancers. We show that IB reduced cell growth, migration and invasion of breast cancer cells. Systemic delivery of IB using nanoparticle-based drug delivery approach suppressed breast cancer growth and metastasis without inducing any toxicity in pre-clinical orthotropic mouse models. Notably, using ex-vivo model of tumor explants from breast cancer patients, we demonstrated that IB inhibited breast cancer growth without affecting normal mammary epithelial cell proliferation. Furthermore, IB improved the sensitivity of breast cancer cells to chemotherapy drugs paclitaxel and doxorubicin. Our results revealed that IB mediated its anti-tumor effect by targeting genes involved in cell cycle progression, microtubule dynamics and DNA damage surveillance pathway including Forkhead Box M1 (FOXM1), stathmin1, S-phase kinase-associated protein 2 (Skp2) and XRCC3, which we show to be highly expressed in breast cancer patients. Importantly, we demonstrated that IB inhibited breast cancer cell's ability to repair DNA strand breaks by impairing homologous recombination events. These findings highlight the potential of IB to be used as a potent therapeutic regimen for treating breast cancer patients. Since IB-1 is derived from a FDA approved drug it has potential to be rapidly translated to the clinic.
Citation Format: Rajamanickam S, Subbarayalu P, Timilsina S, Gorthi A, Drake MT, Chen Y, Vadlamudi R, Bishop AJR, Arbiser JL, Rao MK. Imipramine Blue - A safe and potent therapeutic regimen that suppresses breast cancer growth and progression by targeting DNA damage surveillance pathway. [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 P4-07-06.
Abstract P4-08-03: DEAD-box RNA helicase DP103 as a novel regulator of Wnt/β-catenin signaling pathway and promotes cancer stem cell-like behavior in triple negative breast cancers
Authors: Cai W , Cheong JK , Edison E , Banerjee A , Tan TZ , Gaboury L , Yousef EM , Thiery JP , Lobie PE , Virshup DM , Yap CT , Kumar AP 
Published: May 2016

Abstract
Despite recent advances in breast cancer therapeutics, mortality of metastatic triple negative breast cancer (TNBC) subtype remains high; due to their lack of hormone receptors expression for targeted therapy. Aberrant activation of Wnt/β-catenin signaling has been associated with breast cancers; where 40% of total breast cancers have elevated β-catenin levels with increased Wnt activity. Recently, we identified DEAD-box RNA helicase DP103 as a novel prognostic biomarker and metastasis-driving oncogene; highly expressed in TNBC subtype. Interestingly, we found high DP103 expression to be positively correlated with high β-catenin expression in clinical specimens (n=400). This led us to hypothesize a possible role of DP103 in modulating the Wnt/β-catenin pathway in TNBCs. Depletion of DP103 in metastatic TNBC cells decreases Wnt/β-catenin activity and expression of downstream Wnt target genes, while overexpression of DP103 increases Wnt activity. Depletion of DP103 also decreases phosphorylation of LRP6 and several important Wnt modulators required for downstream Wnt activation. Moreover, induction of Wnt/β-catenin signaling in Wnt responsive TNBC cells also significantly increased DP103 expression, indicating a possible positive feedback loop. Both canonical and non-canonical Wnt signaling is known to independently promote stem cell growth in mammospheres. Herein, we will also provide evidence on the role of DP103 in promoting breast cancer stem cell-like properties. Collectively, our data show a novel regulatory role of DP103 in the Wnt/β-catenin signaling pathway and in promoting breast cancer stem cell-like behavior, presenting itself as a potential drug target in TNBC patients.
Citation Format: Cai W, Cheong JK, Edison E, Banerjee A, Tan TZ, Gaboury L, Yousef EM, Thiery JP, Lobie PE, Virshup DM, Yap CT, Kumar AP. DEAD-box RNA helicase DP103 as a novel regulator of Wnt/β-catenin signaling pathway and promotes cancer stem cell-like behavior in triple negative breast cancers. [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 P4-08-03.
Abstract P4-09-06: The prognostic role of RANK single nucleotide polymorphisms in breast cancer patients with bone metastases
Authors: Casimiro S , Ferreira A , Alho I , Melo M , Brás R , Costa AL , Sousa AR , Mansinho A , Abreu C , Pulido C , Macedo D , Pacheco TR , Costa L 
Published: May 2016

Abstract
Background: Receptor activator of NF-kB (RANK) pathway regulates bone remodeling and is involved in breast cancer (BC) progression. RANK over-expression in primary BC associates with poor prognosis and metastasis development. In patients with BC, RANK and RANK-ligand (RANKL) single nucleotide polymorphisms (SNPs) have also been associated with BC risk and bone metastasis (BM)-free survival , respectively. Here we analyze the association of five RANK missense SNPs with prognosis of patients with BM from BC.
Methods: Missense RANK SNPs (rs34945627, rs12721431, rs35184120, rs35993683, rs61751992) were genotyped in germline DNA from a retrospective cohort of 76 patients with BM from BC, under bisphosphonates; and a cohort of 80 healthy volunteers (samples from Biobanco-IMM, Lisbon, Portugal). Genotypic allelic frequencies were assessed using TaqMan assays (Applied Biosystems). SNP rs34945627 was analyzed with regard to clinicopathological characteristics, skeletal-related events (SRE), bone progression-free interval (BPFi), and overall survival (OS). Univariate association with clinicopathological characteristics was performed using Fisher's exact test and Wilcoxon rank-sum test; univariate differences between survival rates were tested for significance using the log-rank test, while multivariate analysis for survival was tested using Cox proportional hazards models.
Results: SNP rs34945627 had a minor allele frequency of 11.84% (n=9) in BC patients versus 1.25% (n=1) in healthy individuals, whereas the remaining SNPs had a minor allele frequency of 2.60% (n=2) in BC patients. Therefore, for inferential analysis only SNP rs34945627 was considered. No differences between alleles were observed regarding clinicopathological characteristics, including treatment. Homozygous patients (CC) had increased OS when compared to heterozygous patients (CT) controlling for age at diagnosis, visceral involvement, radiographic pattern of BM and baseline urine NTX (adjusted HR 5.76, 95% CI 2.10-15.81; p&lt;0.001). No association could be seen with regard to SREs (adjusted HR 1.43, 95% CI 0.46-4.46; p=0.54) or BPFi (adjusted HR 0.26, 95% CI 0.06-1.17; p=0.08).
Conclusions: RANK SNP rs34945627 seems to be a marker of poor prognosis in patients with BC and BM. Further studies are required to characterize the biological and clinical significance of this finding.
Citation Format: Casimiro S, Ferreira A, Alho I, Melo M, Brás R, Costa AL, Sousa AR, Mansinho A, Abreu C, Pulido C, Macedo D, Pacheco TR, Costa L. The prognostic role of RANK single nucleotide polymorphisms in breast cancer patients with bone metastases. [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 P4-09-06.
Abstract P4-09-11: microRNA markers and risk of recurrence in women with ductal carcinoma in situ
Authors: Liu Y , Baker C , Wang X , Colditz G 
Published: May 2016

Abstract
Background: Women with DCIS have increased risk for invasive breast cancer. Limited abilities to accurately identify aggressive DCIS have resulted in inappropriate treatment for many women with mammographically-detected DCIS. miRNAs play a critical role in tumorigenesis. It remains unknown if miRNAs are associated with recurrence and refine risk assessment for DCIS patients.
Methods: The study included 16 DCIS cases that developed ipsilateral recurrence (cases) and 32 DCIS cases that did not develop any type of recurrence (controls). Cases and controls were treated with breast conserving surgery and matched on age, race, and year of diagnosis. Expression of 96 cancer-related miRNAs was quantified using RT-PCR.
Results: Two miRNAs were differentially expressed between cases and controls (p&lt;0.05). A combination of the two miRNA markers was significantly associated with recurrence risk (odd ratio=2.60 per 1-unit increase, 95% confidence interval=1.14-8.13), which was independent of family history of breast cancer, radiation and endocrine therapy. The miRNA-based score (c-statistic=0.73) performed better than individual miRNAs (c-statistic=0.64-0.69) in discriminating DCIS cases who did and did not develop recurrence.
Conclusion: miRNA expression in DCIS was associated with recurrence risk, which warrants further investigations to identify new miRNA markers by including more DCIS cases and analyzing all breast cancer-related miRNAs.
Citation Format: Liu Y, Baker C, Wang X, Colditz G. microRNA markers and risk of recurrence in women with ductal carcinoma in situ. [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 P4-09-11.
Abstract P4-09-15: BRCAness and PD-L1 expression of basal-like and not basal-like triple negative breast cancer
Authors: Mori H , Kubo M , Yamada M , Kai M , Osako T , Nishimura R , Arima N , Okido M , Kuroki S , Oda Y , Nakamura M 
Published: May 2016

Abstract
Background: Triple Negative Breast Cancer (TNBC) subtype occurs in approximately 20% of all patients with breast cancer and is associated with rapid growth, early metastasis and poor prognosis compared with other subtypes. TNBCs are a heterogeneous disease entity and further subclassification is needed, but still ongoing. In this study, we assessed BRCAness, defined as shared characteristics between sporadic and BRCA1-mutated tumors, in a cohort of basal-like and non-basal-like TNBCs.
Patients and Methods: DNA was isolated from formalin-fixed paraffin-embedded tumor tissues and BRCAness status was analyzed in 262 patients with primary TNBCs resected at our three hospitals between 2004 and 2014. Classification of BRCAness was performed by using Multiple Ligation-dependent Probe Amplification (MLPA) with the probemix P376 BRCA1ness by MRC (Amsterdam, Holland). The tumor subtypes were routinely determined immunohistochemically by using resected specimens. Basal-like phenotype was defined as being positive for Epidermal Growth Factor Receptor (EGFR) and/or Cytokeratin 5/6 (CK5/6). Moreover, TNBCs were stained and analyzed for programmed cell death ligand-1 (PD-L1) expression as a target of new immune therapies.
Results: Of 262 TNBCs, 232 tumors (88.5%) was a basal-like phenotype. The results of MLPA assay showed that 159 (68.5%) of 232 tumors had a BRCAness profile. Patients with basal-like BRCAness tumors were younger than patients with basal-like non-BRCAness tumors (p&lt;0.0001). There was no significant difference between the two groups regarding pathological stage. The basal-like BRCAness group had shorter relapse-free survival (RFS) and overall survival (OS) than the basal-like non-BRCAness group (p=0.028 and p=0.13, respectively), and anthracycline-based regimens provided greater benefit to the basal-like BRCAness group significantly (p=0.01 in RFS and p=0.007 in OS). PD-L1 was expressed in 71 (44.7%) of 159 basal-like TNBCs with BRCAness.
Conclusion: We reported the majority of basal-like TNBCs showed a BRCAness profile and PD-L1 expressed in approximately 50% of BRCAness tumors. It is known that about 30% of BRCAness tumors are BRCA1-mutated tumors. Those biomarkers are essential for subclassification of TNBCs and may offer not only platinum-based chemotherapy but also novel therapies, such as immune-targeted therapies of PD-1/PD-L1 inhibitors and PARP inhibitors, to patients with basal-like TNBCs with BRCAness.
Citation Format: Mori H, Kubo M, Yamada M, Kai M, Osako T, Nishimura R, Arima N, Okido M, Kuroki S, Oda Y, Nakamura M. BRCAness and PD-L1 expression of basal-like and not basal-like 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 P4-09-15.
Abstract P4-09-27: ABC transporter expression: Clues into chemoresistance of triple negative breast cancers
Authors: Feldman R , Abbott B , Reddy S , Gatalica Z , Castro M 
Published: May 2016

Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive histological subtype with high rates of recurrence and metastatic disease. Intrinsic or acquired multidrug resistance facilitated by the over-expression of drug efflux pumps (ABC transporters: BCRP [ABCG2], MRP1 [ABCC1] and PGP [ABCB1]), may contribute to the aggressive nature of this disease. We examined the expression patterns of drug efflux pumps for insight on their potential role in chemoresistance of TNBC.
Methods: 1393 TNBC patients molecularly profiled with a commercial assay (Caris Life Sciences) were evaluated retrospectively for expression of BCRP, MRP1 and PGP by immunohistochemistry. Antibodies used: PGP (C494), BCRP (6D171) and MRP1 (33A6). IHC threshold: positive = ≥1+ and ≥10%). This data set also included metachronous paired samples from 71 TNBC patients. JMP was used to ascertain distributional differences.
Results: PGP and MRP1 positive expression rates were 8.4% (117/1393) compared to 78.2% (248/317), respectively, displaying an inverse association (p=0.0001). BCRP was over-expressed in 52% (90/173). Co-expression data for all three transporters was available for 153 patients. BCRP/MRP1 co-expression was most abundant, 39% (59/153), followed by MRP1/PGP at 4% (6/153) and BCRP/PGP at 2% (3/153). Furthermore, 12% (18/153) of TNBC exhibited positive expression for all three drug pumps (16/18 or 89% were from patients with metastatic disease) and 14% (22/153) exhibited negative expression for all three drug pumps (15/22 or 68% were from patients with metastatic disease). Interestingly, positive MRP1 status, but not BCRP or PGP, correlated with metastatic disease (p=0.0061). In the paired data analysis, PGP expression was absent in 77% (55/71) and retained lack of expression in subsequently profiled specimens, 3% (2/71) retained positive PGP status, 13% (9/71) lost expression of PGP and 7% (5/71) gained expression of PGP. 36/40 patients that lacked PGP expression and 8/9 patients that "lost" PGP expression, exhibited and retained expression of MRP1 in the initial and subsequently-profiled specimens.
Conclusion: Biomarker expression patterns of drug efflux pumps may provide insight to the chemoresistance phenotype observed in TNBC. Expression of MRP1 is favored in TNBC and is correlated with metastatic disease status. Although PGP expression may be absent or lost during TNBC progression, MRP1 (and BCRP) expression are almost always retained. Utilization of chemotherapies that are substrates of PGP, but not MRP1, (based on expression status) may be worthy of future investigation.
Citation Format: Feldman R, Abbott B, Reddy S, Gatalica Z, Castro M. ABC transporter expression: Clues into chemoresistance of triple negative breast cancers. [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 P4-09-27.
Abstract P4-10-02: Cancer team approach for implementing survivorship care plans in the breast cancer survivorship clinic
Authors: Danciu OC , Bharadwaj SN , Hoskins K 
Published: May 2016

Abstract
Background: Recommendations from the Institute of Medicine are that cancer patients receive individualized survivorship care plan (SCP) and treatment summary. SCP includes guidelines for monitoring and maintaining health and is a communication tool shared with families and health care providers. Offering SCP and treatment summary to cancer survivors remains challenging due to time and resource limitations, inadequate reimbursement and survivor access.
Methods: Survivorship starts when completing the initial treatment (surgery, chemotherapy or radiation therapy). A team of medical oncologists, nurse practitioner and patient navigator created a process of pre-screening and identifying breast cancer (BC) survivors. SCP and treatment summary were pre-populated, individualized for each patient, then finalized and discussed with the patients during their medical oncology clinic visit. Pre intervention data was retrospectively collected, including all BC cases from March 2014 to March 2015. Post intervention data was prospectively collected over eight weeks. Pre and post intervention SCP completion rates were compared with chi square analysis.
Results: A baseline one year review of 1124 encounters noted 23 of 90 (25%) BC survivors received SCP. Ninety-six encounters occurred during the 8 week pilot period. Sixteen (16.6%) cases met the definition of BC survivor. During the pilot period, 15 out of 16 (93.7%) survivors received the SCP and treatment summary (p &lt;0.0001). After the pilot period, 96.4% of BC survivors were seen in the BC survivorship clinic.
Conclusions: We successfully piloted the implementation of SCP for BC survivors. Our team found that using clinic visit screening and pre-identifying patients that transition into the survivorship program resulted in improvement of compliance with survivorship measures. In BC survivorship clinic we address specific survivorship issues and review SCP and treatment summary.
Citation Format: Danciu OC, Bharadwaj SN, Hoskins K. Cancer team approach for implementing survivorship care plans in the breast cancer survivorship clinic. [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 P4-10-02.
Abstract P5-01-10: Correlation of apparent diffusion coefficient with standardized uptake value in invasive lobular carcinoma of breast using in hybrid 18F-FDG PET/MR
Authors: Choi JE , Kang SH , Lee SJ , Kong EJ 
Published: May 2016

Abstract
Purpose: To compare the apparent diffusion coefficient (ADC) with maximum standardized uptake values (SUV) derived from combined 18F-FDG PET/MRI in invasive lobular carcinoma (ILC) patients.
Methods: From 2012 Aug to 2015 Feb, 53 women with histologically proven ILC (mean age, 50.3 ± 7.7 y-o) underwent hybrid 18F-FDG PET/MR (Siemens Biograph mMR) scan for preoperative assessment. During PET acquisition, simultaneous diffusion-weighted imaging (DWI, b values: 0, 400, 800 s/mm2) was performed using breast coil. ILC over than 2 Cm in size were analyzed. Regions of interest (ROI) were drawn covering the entire ILC on the attenuation-corrected PET-image and the monoexponential ADC-map on PET/MR workstation. All the patients were received surgical treatment within 3 weeks after scan. Spearman rank correlation coefficient (ρ) was calculated to examine the correlation between SUVmax and ADC value.
Results: Total 25 ILC (5.4±1.3 cm; 2.1-6.3 cm) of 22 women were enrolled. 24 ILC showed ER (+)/PR (+) and all ILC showed HER2 (-). 15 patients were confirmed metastatic axillary lymph nodes. The mean of SUVmax was 2.14 ± 2.2 (0.91-11.9) and mean of ADC was 1.02 ×10-3 (0.82 -1.31 ×10-3) mm2/s. Higher histologic grade was correlated with higher SUV (ρ = -0.6, p=0.001). And SUV showed inverse correlation with ADC (ρ = -0.48, p=0.016).
Conclusion: The present data show inverse correlation between increased glucose-metabolism and cellularity in ILC patients. 18F-FDG PET and DWI thus may offer complementary information for the evaluation of treatment response in ILC.
Citation Format: Choi JE, Kang SH, Lee SJ, Kong EJ. Correlation of apparent diffusion coefficient with standardized uptake value in invasive lobular carcinoma of breast using in hybrid 18F-FDG PET/MR. [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 P5-01-10.