bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-01-17: Expression of circulating tumor cells (CTC) and CK-19 mRNA (CK19) as prognostic factors in heavily pretreated metastatic breast cancer
Authors: Morales Serafin , Velasco Ana , Vidal Jose , Serrate Anna , Valls Joan , Samame Juan Carlos , Gisbert Rafael , Moral Desamparados , Llombart Antonio , Salud Antonieta , Matias-Guiu Xavier 
Published: May 2015

Abstract
Introduction: The expression of CTC and CK19 holds prognostic value for patients with breast cancer but their clinical significance remains still controversial.
Methods: This clinical observational study included 58 preteated metastatic breast cancer patients who started a standard new treatment line. CTC and CK19 was measured with CellSearch® and RT-PCR respectively at inclusion time. Progression-free survival (PFS) was defined as the time elapsed between the initiation of the treatment and either the date of clinical or radiological progression or death or the last follow-up. Cox proportional hazards regression model was used to assess the univariate prognose value of CTC and CK19 on PFS, and Kaplan-Meier estimates. A multivariate Cox model was also performed to additionaly account for ER and visceral disease. CTC and CK19 positivity was considered when a value of 1 or more was observed.
Results: Mean age was 59.68 (range 35-86), the average number of previous treatments was 2.98 (range 1-10), 38 patients (65.52%) were ER+ and 22 (37.93%) had visceral disease. Median PFS was 7 months (CI 95% 4-9). Univariate analyses showed a significant effect of the positivity of CK19 (HR=2.22, CI 95% 1.15-4.29, p=0.01) but did not reach statistical significance for CTC (HR=1.86, CI 95% 0.93-3.72, p=0.07). The estimate disease-free survival rate at 6 and 12 months were 63.6% and 43.4% for patients with CK19&lt;1 and 47.1% and 10.6% for patients with CK19&gt;=1, respectively. The estimate disease-free survival rate at 6 and 12 months were 77.8% and 28.8% for patients with CTC=0 and 43.6% and 21.5% for patients with CTC&gt;=1, respectively. In the multivariate analysis the effect of CK19 and CTC were similar (HR=2.12 and 1.86, p=0.03 and 0.08 respectively), ER was statistically significant (HR=0.48, p=0.05, + vs -) but visceral diseases appeared not significant (HR=1.57, p=0.17, yes vs no).
Conclusions: The expression of CK19 appeared clinically meaningful in pretreated metastatic breast cancer patients, even when adjusting by ER and visceral diseases. CTC showed a similar but minor effect and not statistically significant. These results support CK19 as an interesting biomarker for predicting clinical response in metastatic breast cancer.
Citation Format: Serafin Morales, Ana Velasco, Jose Vidal, Anna Serrate, Joan Valls, Juan Carlos Samame, Rafael Gisbert, Desamparados Moral, Antonio Llombart, Antonieta Salud, Xavier Matias-Guiu. Expression of circulating tumor cells (CTC) and CK-19 mRNA (CK19) as prognostic factors in heavily pretreated metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-17.
Abstract P4-04-20: Tumor infiltrating lymphocytes in inflammatory breast cancer
Authors: Colpaert Cecile , Marsan Melike , Vermeulen Peter , Dirix Luc , Van Laere Steven ,   Inflammatory Breast Cancer International Consortium
Published: May 2015

Abstract
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer with poor prognosis. Multimodal treatment including neo-adjuvant chemotherapy is the treatment of choice for IBC patients, with pathological complete response (pCR) being one of the most important prognostic factors.
Tumor infiltrating lymphocytes (TILs) are an independent predictor of response to neo-adjuvant chemotherapy in breast cancer (Denkert C. et al., 2010). In a search for multigene predictors of pCR in IBC using DNA micro-arrays, a 107 gene signature was found that distinguished between responders and non-responders. This signature was enriched for immunity-related genes showing that in IBC, as in non-IBC, response to neo-adjuvant chemotherapy is associated with immunity related processes (Bertucci F. et al., 2014).
Standard H&E stained sections of formalin-fixed paraffin-embedded pre-treatment tumor tissue of 77 IBC patients were used to evaluate the presence of TILs according to the Denkert method: mononuclear cell infiltrates were considered to be intratumoral TILs when making direct contact with the tumor cells, while stromal TILs are mononuclear cells being present in the tumor stroma without making direct contact with tumor cells.
Intratumoral TILs were observed in 10,4% (8/77) of the patients. Stromal TILs (strTILs ) were present in all tumors: in 35% (27/77) strTILs occupied less than 5% of the tumor stroma, in 62 % (48/77) strTILs occupied between 5 and 50% of the tumor stroma and 2,6% (2/77) were "lymphocyte predominant breast cancers (LPBC)" with strTILS occupying more than 50% of the tumor stroma. One LPBC was HER2 positive, the other one was triple negative. There was a significant association of strTILs with response to neo-adjuvant chemotherapy: pCR was obtained in 13% of the patients with strTILs &lt;5%, in 20% of the patients with strTILs between 5 and 50% and in both patients with LPBC (Chi 2 p=0,018).
Tertiary lymphoid structures - lymphoid follicles with germinal centres, known to be associated with better clinical outcomes (Gu-Trantien C. et al., 2013) - were detected in 2.6% of the patients (2/77); both patients had a disease free survival of more than 3 years.
This study shows that IBC tumors do not contain more TILs than non-IBC tumors and that, as in non-IBC, there is a positive association of stromal TILs with pCR in IBC. Further validation of these results and further study of lymphocyte subsets in IBC is warranted.
Citation Format: Cecile Colpaert, Melike Marsan, Peter Vermeulen, Luc Dirix, Steven Van Laere, Inflammatory Breast Cancer International Consortium. Tumor infiltrating lymphocytes in inflammatory breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-20.
Abstract P4-04-28: Weight loss reversed the carcinogenic effect of obesity on basal-like breast cancer
Authors: Qin Yuanyuan , Sundaram Sneha , Zhao Liyang , Essaid Luma , McNaughton Kirk K , Bendt Katharine M , Darr David B , Troester Melissa A , Makowski Liza 
Published: May 2015

Abstract
Epidemiologic studies demonstrate that obesity is associated with a subtype of breast cancer called basal-like breast cancer (BBC), which is fast proliferating and aggressive, with no targeted therapies. Using the C3(1)-TAg murine model of BBC, we have previously shown that obese adult mice displayed significantly decreased tumor latency compared to lean mice with induction of the oncogenic HGF/c-Met pathway. Reducing adiposity is predicted to lower incidence of BBC in human population studies. Thus, the objective of this study was to investigate how a diet-switch to reduce obesity affected BBC onset and early progression. C3(1)-TAg mice were placed on a control low fat diet (LFD) and remained lean, high-fat diet (HFD) to induce obesity, and a group made obese by HFD that were then switched to LFD to induce weight loss. Just two weeks after weight loss, mice in the diet switch group had weights and adiposity similar to lean mice. Weight loss caused a 51.4% decrease in adiposity (P&lt;0.0001) compared to obese mice. Importantly, mice that lost weight displayed significantly delayed tumor latency (17 week) compared to obese mice on HFD (15 week), with no differences detected in tumor burden or growth. Therefore the obese microenvironment that promotes early tumor onset can be reprogrammed with weight loss and restoration of a lean phenotype. Ongoing studies are examining HGF/cMet expression by immunohistochemistry in normal mammary glands and tumors to determine the contribution of this obesity-responsive pathway. Metabolomics and RNAseq analysis will identify novel obesity-dependent pathways relevant to BBC. In conclusion, we demonstrated that loss of adiposity protected against early BBC onset. Further research will identify important biomarkers associated with obesity and weight loss that can be compared through conserved biology approaches.
Citation Format: Yuanyuan Qin, Sneha Sundaram, Liyang Zhao, Luma Essaid, Kirk K McNaughton, Katharine M Bendt, David B Darr, Melissa A Troester, Liza Makowski. Weight loss reversed the carcinogenic effect of obesity on basal-like breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-28.
Abstract P4-05-01: Genetic analysis of the role of Brca1 in suppression of basal-like breast cancer
Authors: Pei Xin-Hai , Bai Feng , Chan Ho Lam , Scott Alexandria , Smith Matthew D , Fan Cheng , Herschkowitz Jason I , Perou Charles M , Livingstone Alan S , Robbins David J , Capobianco Anthony J 
Published: May 2015

Abstract
BRCA1 mutation carriers are predisposed to developing basal-like breast cancers with high metastasis and poor prognosis. However, the mechanism underlying the function of BRCA1 in suppressing basal-like breast cancer remains unclear.
We previously reported that deletion of p18Ink4c (p18), an inhibitor of CDK4 and CDK6, functionally inactivates the RB pathway, stimulates mammary luminal stem cell proliferation, and leads to spontaneous luminal tumor development whereas germline mutation of Brca1 alters the fate of luminal cells and causes luminal-to-basal mammary tumor transformation. We report here that disruption of Brca1 by both germline and epithelium-specific mutation of Brca1 in p18 deficient mice activates epithelial-to-mesenchymal transition (EMT) and induces basal-like breast tumors. Introduction of BRCA1 suppresses expression of EMT-inducing transcription factors (EMT-TFs) and inhibits EMT in mammary tumor cells. Knockdown of BRCA1 in human luminal cancer cells activates EMT and increases tumor formation potential. Consistently, EMT features are inversely correlated with BRCA1 in human breast cancers. These findings provide genetic evidence suggesting that BRCA1 suppresses EMT and inhibits basal-like tumor development.
Citation Format: Xin-Hai Pei, Feng Bai, Ho Lam Chan, Alexandria Scott, Matthew D Smith, Cheng Fan, Jason I Herschkowitz, Charles M Perou, Alan S Livingstone, David J Robbins, Anthony J Capobianco. Genetic analysis of the role of Brca1 in suppression of basal-like breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-01.
Abstract P4-05-05: A novel TP53-dependent role for TLR4 in driving breast cancer
Authors: Haricharan Svasti , Brown Powel H 
Published: May 2015

Abstract
Breast cancer is a leading cause of cancer-related death. Toll-like receptor (TLR)-4 is an important mediator of cytokine secretion that is expressed in breast cancer cells, and is frequently mutated in a subset of breast tumors associated with high mutation load and poor patient survival. We show here that TLR4 plays an important role in driving breast cancer growth in a TP53 context-dependent manner. Using siRNA mediated knockdown, pharmacological inhibition and hyperactivation of TLR4 we demonstrate that TLR4 inhibits growth in breast cancer cells with wildtype TP53 by inducing G0/G1 arrest and decreasing mitotic entry. Conversely, in breast cancer cells with mutant TP53, TLR4 acts as an oncogene and drives cell growth by inducing mitosis. Furthermore, we identify the underlying mechanism for this dual TP53-dependent effect of TLR4 on breast cancer cell growth: differential interferon gamma (IFN-γ) secretion by tumor cells into their microenvironment. Hyperactivated TLR4 signaling in TP53 wildtype breast cancer cells results in increased IFN-γ secretion, identified by an unbiased cytokine array and validated by ELISA, thus inhibiting growth in an autocrine/paracrine fashion. Moreover, secreted IFN-γ is both necessary and sufficient for TLR4-induced growth inhibition in TP53 wildtype breast cancer cells. Finally, the dual TP53-dependent effect of TLR4 extrapolates to several other cancer types in silico, attaching potentially global significance to these results. Taken together, the data presented in this paper strongly suggest a novel role for TLR4 as a suppressor of cell growth in TP53 wildtype tumors, and identify differential IFN-γ secretion as the underlying mechanism. The results of this study are also translationally relevant, delineating the TP53 mutant breast cancer subset as a group that can benefit from pharmacological TLR4 inhibition. Most importantly, these results indicate a need for studying the effect of drivers of cancer growth pleiotropically rather than as isolated events.
Citation Format: Svasti Haricharan, Powel H Brown. A novel TP53-dependent role for TLR4 in driving breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-05.
Abstract P4-05-10: PRKCQ, a novel protein kinase C preferentially expressed in triple negative breast cancer, drives oncogenic growth, survival and migration
Authors: Irie Hanna Y , Halstead-Nussloch Gwyneth , Ito Koichi 
Published: May 2015

Abstract
Background/Rationale: PRKCQ, a member of the novel protein kinase C family, was identified in a functional genomic screen for regulators of anoikis resistance/anchorage-independent survival (Irie et al., 2010). Interestingly, it is preferentially expressed in the triple negative/basal subtype of breast tumors compared to Luminal or Her2+ tumors. We sought to determine the functional role of PRKCQ in triple negative breast cancer and evaluate PRKCQ as a candidate therapeutic target for this subtype. Materials and Methods. Consistent with its expression in triple negative patient breast tumors, PRKCQ is also highly expressed in several triple negative breast cancer cell lines. We utilized both gain- and loss-of-function approaches in these cell lines to determine the requirement for PRKCQ in oncogenic growth and survival using in vitro and in vivo models. Results. Isoform-specific downregulation of PRKCQ using shRNA vectors severely impaired growth of triple negative breast cancer cells in 2D monolayer and 3D Matrigel cultures. In 3D cultures, PRKCQ downregulation not only inhibited growth, but impaired the formation of invasive branching. PRKCQ downregulation also inhibited the growth of MDA231 primary tumor xenografts. All of these data support a requirement for PRKCQ expression in triple negative breast cancer cell growth. To determine if PRKCQ is sufficient to drive oncogenic phenotypes, we overexpressed PRKCQ in a non-transformed immortalized breast epithelial cell line, MCF-10A. PRKCQ expression conferred EGF-independent growth, migration and anoikis resistance. In PRKCQ-expressing MCF-10A cells, EGFR phosphorylation and activation were preserved in the absence of exogenous EGF ligand addition. We are currently elucidating the mechanisms responsible for PRKCQ-mediated, sustained activation of EGFR. Conclusions. PRKCQ is critically required for growth of triple negative breast cancer cells. Increased expression of PRKCQ is sufficient to drive oncogenic, growth factor-independent growth, survival and migration. Interestingly, PRKCQ could play a dual role in the development of triple negative breast cancer, as it may also function in the immune microenvironment to support the growth of these tumors. Therefore, PRKCQ is an attractive candidate therapeutic target for patients with triple negative breast cancer.
Citation Format: Hanna Y Irie, Gwyneth Halstead-Nussloch, Koichi Ito. PRKCQ, a novel protein kinase C preferentially expressed in triple negative breast cancer, drives oncogenic growth, survival and migration [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-10.
Abstract P4-05-17: Mammaglobin is a potent regulator of breast cancer processes leading to disease progression
Authors: Guerrette Roxann , Picot Nadia , Robichaud Gilles 
Published: May 2015

Abstract
Metastasis is the major cause of death in women suffering from breast cancer. To provide a better understand breast cancer progression, we have studied the role of mammaglobine-1 (MGB1) gene in breast cancer pathogenesis. MGB1 has been extensively studied as a diagnostic biomarker due to its abundant expression in mammary cancer cells. Yet, MGB1's role in disease progression is still unknown. Our experimental results demonstrate for the first time that MGB1 in a pivotal regulator on breast cancer malignancy. More precisely, loss of MGB1 expression correlates with a decrease in proliferation, spheroid formation, migration, and invasion capacities of breast cancer cells. Concomitantly, we also observe that MGB1 expression activates pro-malignant signaling cascades such as MAPKs, focal adhesion kinase (FAK) and NFkB pathways. Moreover, MGB1 promote epithelial to mesenchymal (EMT) features which coincide with our findings. Our study provides the first evidence for MGB1 as regulator of breast cancer malignancy and disease progression.
Citation Format: Roxann Guerrette, Nadia Picot, Gilles Robichaud. Mammaglobin is a potent regulator of breast cancer processes leading to disease progression [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-17.
Abstract P4-07-01: Calorie restriction normalizes global microRNA expression by preventing the loss of dicer expression during mammary tumorigenesis
Authors: Devlin Kaylyn L , Sanford Tiffany , Mambo Elizabeth , Hursting Stephen D 
Published: May 2015

Abstract
MicroRNA (miRNAs) are small, post-transcriptional regulators that play an integral role in maintenance of cellular functions and whose dyregulation has been shown to promote many types of cancer, including breast cancer. Global downregulation of miRNAs has emerged as a common theme in human breast tumors and has been shown to contribute to oncogenesis. One of the primary mechanisms through which miRNAs are globally dysregulated is downregulation of enzymes involved in miRNA biogenesis. We aim to establish how calorie restriction (CR), which potently inhibits breast cancer progression, regulates global miRNA expression and miRNA biogenesis enzyme functionality in mammary tumors. To address these questions, 100 female Sprague Dawley rats were administered either dimethylbenz(a)anthracene (DMBA) or vehicle control at 50 days of age, then randomized to receive either control (AIN-76A) diet ad-libitum (n=40) or a 30% CR diet regiment (n=60). Resultant mammary tumors were allowed to develop for 12 weeks. Calorie restriction significantly increased survival to study endpoint relative to control diet (75% vs 35%, respectively) (p=0.0047). Furthermore, of the animals that developed tumors, CR significantly decreased median tumor area by 56% compared to control diet (109.4 mm2 vs 250.9 mm2, respectively) (p=0.0286). Global miRNA expression was analyzed through miRNA-specific sequencing. Calorie restriction had a broad effect on miRNA expression, illustrated by the fact that of all the miRNAs with a greater than two-fold expression difference between CR and control, 80% are overexpressed in CR tumors compared to control tumors. These results can be explained by the additional finding that CR was able to prevent the loss of Dicer expression, a key miRNA biogenesis enzyme, observed in control-fed mammary tumor tissue compared to normal tissue. This important finding suggests that global miRNA normalization through the retention of Dicer expression during cancer progression could be a contributing mechanism to CR’s anticancer effects. We plan to further these investigations by exogenously manipulating Dicer expression in Rama25 cells, which were originally derived from a DMBA-induced mammary tumor from a Sprague Dawley rat, and analyzing the resultant tumorigenic potential in vitro and in vivo. The results obtained will provide insights into the mechanisms of breast cancer progression and how CR inhibits progression through microRNA modulation.
Citation Format: Kaylyn L Devlin, Tiffany Sanford, Elizabeth Mambo, Stephen D Hursting. Calorie restriction normalizes global microRNA expression by preventing the loss of dicer expression during mammary tumorigenesis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-07-01.
Abstract P4-11-02: Worse breast cancer prognosis in insulin treated diabetic patients - A population based registry study in Sweden
Authors: Olsson Håkan , Einefors Rickard , Broberg Per , Landin Olsson Mona 
Published: May 2015

Abstract
Background. Diabetes may be linked to incidence of different tumor diseases and prognosis through various mechanisms such as the disease itself, hyperglycemia, obesity and anti-diabetes therapy.
Material and methods. The study includes all women with BC diagnosed in Sweden between 2000 through 2008 (n=54406). The women had no previous cancer diagnosis during the period of 1958-1999. Dates of birth, BC diagnosis and TNM-stage where directly extracted from the cancer registry. The women’s anti-diabetes therapy was gathered from the Swedish Prescribed Drug Registry. Information regarding the cause of death and date of death was obtained from the Cause of Death Registry and tbe Swedish Population Register up until the 31st of December 2012 and 31st of December 2013 respectively. Analyses have been restricted to patients receiving insulin therapy (n=2463) and their breast cancer prognosis has been calculated in comparison with breast cancer patients without diabetes. All analyses were adjusted for TNM-stage and age at diagnosis.
Results. Patients with insulin treated diabetes had a worse prognosis compared with other women with breast cancer (HR 1.7, 95%CI 1.5-2.0). The worse prognosis could be seen both for patients with ER+ and ER- tumors. The worst prognosis was seen for patients treated with NPH insulins (HR 2.8, 95% CI 2.4-3.3) while patients treated with long-acting insulin analogs had an intermediate prognosis (HR 1.6, 95% CI 1.2-2.2). Those women treated with NPH insulins and metformin had a slightly worse prognosis (HR 1.4, 95% CI 1.0-1.8). The results for breast cancer specific survival and total survival were similar.
Conclusion. Our results imply that insulin treated breast cancer patients have a worse survival compared with other women with breast cancer regardless of tumor stage. Metformin therapy may partially counteract the association.
Citation Format: Håkan Olsson, Rickard Einefors, Per Broberg, Mona Landin Olsson. Worse breast cancer prognosis in insulin treated diabetic patients - A population based registry study in Sweden [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-02.