bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-13-02: The beliefs, knowledge, understanding, attitudes and treatment access to breast cancer amongst rural women in Northern Nigeria
Authors: Tagbarha Malcolm O 
Published: May 2015

Abstract
Goal: The goal of this study is to ascertain the beliefs, knowledge, understanding, attitudes and treatment access to breast cancer among rural women in Nigeria.
Background: Breast cancer has become a popular topic in recent years with several thousands of women diagnosed to be positive every year. The availability of care/treatment upon early detection is key to survival.
Methods: An interview guide was designed specifically for this study in which 200 rural women in Northern Nigeria, age 45 and over took part in. It contained questions about beliefs, knowledge, understanding and attitudes about Breast Self-Examination (BSE), Clinical Breast Examination (CBE) and mammogram. In addition, questions assessing the variables of the Health Belief Model and health motivations also were included. The data were obtained during face-to-face interviews in the primary language of the participating woman. The interviews were transcribed and translated into English.
Results: Out of the 200 women who participated, only 1% two (2) of the participants practiced BSE monthly, 8% had undergone at least one CBE during their lives, and 91% had never had a mammogram. There were little or no access to treatment even at early detection in these rural areas causing thereby vulnerability to loss of life. Majority of these rural women (95%) said they knew little or nothing about breast cancer. While 15% of the women said detecting cancer early was important, only 3% reported that cancer could be cured. Age, education, or mother tongue showed no statistically significant relationship with the breast health practice scores. However, proficiency with the English language (p = 0.009) and number of years exposed to awareness and education (p = 0.009) had a significant relationship with the breast health practice scores. The significant explanatory factor for the variable breast health practices was a cue to action (p = 0.009).
Conclusions: The level of awareness and treatment access to breast cancer amongst Northern Nigeria’s rural women is extremely low thereby making them not to engage in screening and/or detection practices. This alarming situation calls for urgent intervention of medical/health organizations to provide immediate breast cancer awareness, screening and care so as to reduce incidences or threat at early detection.
Citation Format: Malcolm O Tagbarha. The beliefs, knowledge, understanding, attitudes and treatment access to breast cancer amongst rural women in Northern Nigeria [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 P5-13-02.
Abstract P5-19-12: Subgroup analysis on efficacy in the routine treatment - Results of the 2nd interim analysis of BRAWO, the non-interventional trial "Breast Cancer Treatment with Everolimus and Exemestane for HR+ Women"
Authors: Jackisch Christian , Grischke Eva-Maria , Schneeweiss Andreas , Decker Thomas , Uleer Christoph , Förster Frank , Tomé Oliver , Wimberger Pauline , Kurbacher Christian M , Mueller Bettina , Harbeck Nadia , Mundhenke Christoph , Kuemmel Sherko , Muth Mathias , Kreuzeder Julia , Bloch Wilhelm , Tesch Hans , Lüftner Diana , Schütz Florian , Fasching Peter A 
Published: May 2015

Abstract
Introduction
BRAWO is a German non-interventional study of 3000 patients (pts) with advanced or metastatic, hormone-receptor-positive, HER2-negative breast cancer treated with everolimus (EVE) and exemestane (EXE). We report results of the 2nd preplanned interim analysis (IA) with a data cut-off on 8th July 2014.
Methods
BRAWO collects data on the routine clinical treatment with EVE and EXE at about 400 sites. Main objectives are to extend the knowledge on a) the efficacy in the clinical routine and the impact of physical activity on efficacy and quality of life, b) prophylaxis and management of stomatitis, and c) the sequence of therapy in the clinical routine. The 2nd IA was defined to take place 12 months after the inclusion of the 500. patient into the documentation.
Results
Efficacy data will be reported for the first 500 documented pts. Apart from data on the total study population we will present the PFS results for subgroups including pts with or without prior EXE therapy, with or without prior chemotherapy for the advanced setting, with or without visceral metastasis and with regard to the line of treatment in the advanced setting and the extent of physical activity. The respective summary of adverse events for these patients will be presented as well as results on treatment compliance and dosing. Baseline characteristics and medical history as well as insights into treatment sequences before EVE and EXE will further be shown for all enrolled patients with valid baseline documentation (approx. 1200).
Conclusion
This subgroup analysis will provide insights into the treatment efficacy in the clinical routine and will add to a more comprehensive understanding of the treatment with EVE/EXE.
Citation Format: Christian Jackisch, Eva-Maria Grischke, Andreas Schneeweiss, Thomas Decker, Christoph Uleer, Frank Förster, Oliver Tomé, Pauline Wimberger, Christian M Kurbacher, Bettina Mueller, Nadia Harbeck, Christoph Mundhenke, Sherko Kuemmel, Mathias Muth, Julia Kreuzeder, Wilhelm Bloch, Hans Tesch, Diana Lüftner, Florian Schütz, Peter A Fasching. Subgroup analysis on efficacy in the routine treatment - Results of the 2nd interim analysis of BRAWO, the non-interventional trial "Breast Cancer Treatment with Everolimus and Exemestane for HR+ Women" [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 P5-19-12.
Abstract P5-20-04: Autophagy promotes escape from PI3K inhibition in ER+ breast cancer
Authors: Yang Wei , Miller Todd W 
Published: May 2015

Abstract
PI3K inhibitors have shown promise for the treatment of ER+ breast cancers. Autophagy has been suggested to promote resistance to PI3K inhibitors. Interestingly, cancer cells often exhibit basal levels of autophagy, which is thought to serve as a mechanism to manage oxidative stress and remove damaged organelles (e.g., mitochondria). Pharmacodynamic analysis of the orally available pan-PI3K inhibitor GDC-0941 at low (100 mg/kg) and high (800 mg/kg) doses, and 2 low doses administered 12 hours apart (BID), in combination with fulvestrant in mice bearing MCF-7 xenografts revealed that treatment induced accumulation of LC-3 II (marker of autophagy) after 24-48 h. In ER+ breast cancer cells cultured in hormone-depleted medium, PI3K inhibition gradually induced apoptosis while increasing LC-3 II. Autophagy promotes glucose metabolism, and PI3K activation is a major driver of glucose uptake. We thus hypothesized that inhibition of autophagy will potentiate the anti-tumor effects of PI3K inhibition by suppressing glucose metabolism.
Chloroquine (CQ) is an anti-malarial drug that inhibits autophagy in mammalian cells by an unknown mechanism. CQ inhibited proliferation and autophagy in ER+ breast cancer cells in vitro. CQ treatment potentiated GDC-0941-induced inhibition of cell proliferation and promotion of apoptosis in growth conditions (10% FBS) with or without fulvestrant, and in hormone-depleted conditions (10% DCC-FBS). CQ treatment increased PI3K inhibitor-induced mitochondrial membrane depolarization, suggesting that this drug combination engages an intrinsic apoptotic pathway. PI3K inhibition also induced autophagy in fulvestrant-resistant MCF-7/FR and CAMA-1/FR cells. CQ increased GDC-0941-induced apoptosis in MCF7/FR and CAMA-1/FR cells, offering combined targeting of PI3K and autophagy as a promising therapeutic strategy for the treatment of anti-estrogen resistant breast cancer.
Mice bearing ZR75-1 xenografts are currently being treated with vehicle, CQ (2 mg/day via drinking water), 800 mg/kg GDC-0941 QW, or the combination. Thus far, single-agents treatments significantly inhibit tumor growth. However, the drug combination has not shown synergistic effects in vivo. Analysis of different doses and schedules of GDC-0941 plus CQ, with or without anti-estrogen treatment, is ongoing.
Citation Format: Wei Yang, Todd W Miller. Autophagy promotes escape from PI3K inhibition in ER+ 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 P5-20-04.
Abstract P5-21-09: Oncologist treatment choices in patients with early stage invasive lobular breast carcinoma - a survey
Authors: Jacobs Carmel , Clemons Mark , Ibrahim Mohamed FK , Addison Christina , Caudrelier Jean-Michel , Graham Ian D , Hutton Brain , Arnaout Angel 
Published: May 2015

Abstract
Introduction: Invasive lobular carcinoma (ILC) is common and accounts for 5-15% of all breast cancers. ILC has distinct clinical and histological features that separate it from invasive ductal carcinoma (IDC) with regards to its breast imaging characteristics, patterns of recurrence and sensitivity to systemic therapy. ILC presents challenges to the physician in many aspects of local-regional and systemic therapy choices. We surveyed breast cancer physicians on their beliefs and practice patterns on issues around the management of ILC.
Methods: A questionnaire was developed and circulated electronically using a modified Dillman technique to surgical, radiation, and medical oncologists across Canada and Ireland.
Results: The questionnaire was completed by 91 of 429 physicians (21% response rate). Response rate by specialty was 25/69 (36%), 21/54 (41%) and 45/306 (13%) for surgical, radiation and medical oncologists respectively. Most surgeon responders (77%) would feel "uncomfortable making treatment decisions for ILC with a mammogram alone" and 100% would be "more comfortable with an MRI". Although 55% reported treating ILC as they would IDC, 22% of surgeons will purposefully obtain larger gross margins intra-operatively. Some radiation oncologists believe ILC is an independent risk factor for local-regional recurrence after breast conserving surgery (49%), and after mastectomy (29%). 33% of radiation oncologists would offer radiation therapy after mastectomy specifically because of the ILC subtype even in the absence of usual indications for radiotherapy. Most medical oncologists treat ILC comparably to IDC with the factors having the largest influence on systemic treatment decisions being tumour stage, hormone receptor status and HER-2 status. 51% of medical oncologists treat ILC with adjuvant chemotherapy as they do for IDC at least ‘most of the time’, while 40% use neoadjuvant chemotherapy as frequently as they do for IDC at least ‘most of the time’. 75% of medical oncologists manage the hormonal treatment of ILC as they do IDC ‘most of the time’ or ‘always’.
Conclusions: There remains significant clinical equipoise in the local-regional and systemic management of ILC. This survey has demonstrated wide variations in both beliefs and practices of management for ILC. Clinical guidance, developed on clinical trials specifically assessing the management of ILC, is required.
Citation Format: Carmel Jacobs, Mark Clemons, Mohamed FK Ibrahim, Christina Addison, Jean-Michel Caudrelier, Ian D Graham, Brain Hutton, Angel Arnaout. Oncologist treatment choices in patients with early stage invasive lobular breast carcinoma - a survey [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 P5-21-09.
Abstract P6-01-11: The neuronal protein sortilin is expressed in aggressive breast cancers and participates in tumor cell growth and invasion
Authors: Pundavela Jay , Roselli Severine , Demont Yohann , Faulkner Sam , Attia John , Keene Sheridan , Walker Marjorie M , Hondermarck Hubert 
Published: May 2015

Abstract
The membrane protein sortilin is involved in intracellular trafficking and has emerged as a key player in the regulation of neuronal viability and function. Few studies have suggested that sortilin may also be implicated in cancer, but its expression in human tumors and potential value as a therapeutic target is unknown. In this study, the level of sortilin was analyzed in a series of 318 clinically annotated breast cancers and 53 normal adjacent tissues by immunohistochemistry. Sortilin was specifically localized in epithelial cells and was detected in 65% of cancers compared to 46% of normal tissues (p=0.0088). Sortilin was detected in 79% of invasive ductal carcinomas compared to only 54% of invasive lobular carcinomas (p&lt;0.0001). Interestingly, sortilin was associated with lymph node involvement (p=0.0093), suggesting a relationship with metastatic potential and poor outcome. In Log-Linear modeling, two-way analyses confirmed the association of sortilin with histological type (ductal vs. lobular invasive carcinomas) and lymph node invasion (p=0.002 and p=0.096 respectively). In vitro, sortilin was detected in a range of cancer cell lines using RTPCR and Western-blotting. Functional investigation using RNA interference revealed that a decrease in sortilin level in the highly metastatic breast cancer cell line MDA-MB-231 resulted in a reduced proliferation and invasiveness, but had no effect on cell viability or apoptosis. Together, these data reveal that sortilin is expressed in aggressive breast cancers and is a potential therapeutic target.
Citation Format: Jay Pundavela, Severine Roselli, Yohann Demont, Sam Faulkner, John Attia, Sheridan Keene, Marjorie M Walker, Hubert Hondermarck. The neuronal protein sortilin is expressed in aggressive breast cancers and participates in tumor cell growth and invasion [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 P6-01-11.
Abstract P6-02-03: SUMO Inhibitors affect tumorigenesis of novel breast cancer xenograft model
Authors: Bogachek Maria V , Park Jung M , De Andrade James P , Kulak Mikhail V , White Jeffrey R , Wu Tong , Spanheimer Philip M , Woodfield George W , Bair Thomas B , Olivier Alicia K , Weigel Ronald J 
Published: May 2015

Abstract
A novel basal breast cancer cell line IOWA-1T was derived from chemotherapy resistant locally advanced breast cancer tumor. The cells rapidly form large, skin-eroding xenografts in nude mice. The SUMO inhibitor anacardic acid (AA) effectively cleared CD44+/hi/CD24-/low cancer stem cell (CSC) population in IOWA-1T and BT-20 basal cancer cell lines and delayed tumor outgrowth of basal cancer xenografts. The effect of SUMO inhibitors to clear the CSC population was dependent upon the SUMO unconjugated form of TFAP2A (Bogachek MV et al, Cancer Cell, 2014). Herein we show that tumors that eventually form from IOWA-1T xenografts in mice treated with AA are not capable of developing secondary xenografts, confirming eradication of the CSC population by SUMO inhibitors. As further mechanistic evidence for the SUMO pathway, transient knockdown of UBC9 and PIAS1 SUMOylation enzymes repressed CD44 expression and increased tumor free and overall survival in mice inoculated with IOWA-1T xenografts. Furthermore, CD44 downregulation was demonstrated in IOWA-1T cells after treatment in vitro with UBC9 inhibitor PYR-41 and PIAS1 inhibitor NSC-207895. Overall survival of mice with IOWA-1T xenografts was increased to 43±0.5 and 39±2 days with PYR-41 and NSC-207895 i.p. injections, respectively, compared to a vehicle treated control group 33±1 days (p&lt;0.05). By contrast, doxorubicin treatment was not able to extend survival of mice with IOWA-1T xenografts. These findings establish the class of SUMO inhibitors as potential therapeutic drugs that eliminate the breast CSC population and may be effective in basal breast cancer cases resistant to conventional chemotherapy.
Citation Format: Maria V Bogachek, Jung M Park, James P De Andrade, Mikhail V Kulak, Jeffrey R White, Tong Wu, Philip M Spanheimer, George W Woodfield, Thomas B Bair, Alicia K Olivier, Ronald J Weigel. SUMO Inhibitors affect tumorigenesis of novel breast cancer xenograft model [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 P6-02-03.
Abstract P6-02-07: Targeting triple-negative breast cancer with fibroblast growth factor receptor 2 allosteric inhibitor RPT835
Authors: Tjulandin Sergey A , Tsimafeyeu Ilya V , Byakhov Mikhail Y , Yin Wei , Ludes-Meyers John , Daeyaert Frits 
Published: May 2015

Abstract
Background: FGFR2 is amplified in 4% of triple-negative breast cancers (TNBC). In addition, the mRNA expression levels of FGFR2 were significantly increased in amplified vs nonamplified tumor samples, suggesting a potential role for FGFR2 in TNBC (Turner et al. 2010). We evaluated efficacy of allosteric inhibition of FGFR2 in high- and low-expressing TNBC xenografts.
Methods: Immunocompromised mice were used for xenotransplantation of FGFR2 high-expressing TNBC cells (SUM52PE) or FGFR2 low-expressing TNBC cells (HS578T). Forty animals with measurable tumors were selected on day 10 and randomized into treatment groups (low-molecular weight allosteric inhibitor RPT835, 30 mg/kg; gavage, daily) or vehicle (water; gavage, daily). Measurements of tumor volume (mm3) were performed by digital calipers every 3 days during 40 days after tumor inoculation.
Results: RPT835 significantly inhibited aggressive growth of SUM52PE tumor xenograft (P&lt;0.0001). At study day 31, mean tumor volumes (± SE) were 2712.2±37 mm3 in the vehicle group, and 1080.7±49 mm3 in the study group. In addition, animals of the study group received RPT835 from day 31 to day 40 with disease stabilization (no differences in tumor volume between days 31 and 40, P=0.167). The tumor growth curve shows a nearly exponential increase in median tumor volume up to day 31 in the vehicle group and a high rate of slow growing tumors up to day 40 in the study group. In the HS578T xenograft study differences in tumor volume between study and control groups were weak at day 31 (mean tumor volumes ± SE, 703±89.1 mm3 vs. 1053±179.8 mm3, respectively; P&lt;0.001) and at day 40 (1104±162.2 mm3 vs. 1592±335 mm3; P=0.01).
Conclusions: The allosteric FGFR2 inhibitor RPT835 significantly impacts on growth of FGFR2-expressing TNBC.
Citation Format: Sergey A Tjulandin, Ilya V Tsimafeyeu, Mikhail Y Byakhov, Wei Yin, John Ludes-Meyers, Frits Daeyaert. Targeting triple-negative breast cancer with fibroblast growth factor receptor 2 allosteric inhibitor RPT835 [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 P6-02-07.
Abstract P6-03-02: Functional genomic screening identifies USP11 as a novel therapeutic target in breast cancer
Authors: O'Connor Darran P , Dwane Lisa , O'Connor Aisling E , Dirac Annette M , Bernards Rene , Gallagher William M 
Published: May 2015

Abstract
The estrogen receptor (ER) is the principal driver of growth and differentiation in breast cells and de-regulated receptor function is a key feature of almost 75% of breast cancers. Here, we investigated the role of de-ubiquitinating enzymes (DUBs), which act to remove ubiquitin moieties from proteins, in regulating the transcriptional activity of ER in breast cancer.
To identify DUBs involved in the regulation of ER transcriptional activity, we performed an RNAi loss-of-function screen using a library of shRNA vectors targeting all known human DUB genes (108 genes/432 shRNAs in total). We found that suppression of a number of DUBs markedly repressed or enhanced the activity of an estrogen-response-element (ERE) luciferase reporter to estradiol (E2). In particular, suppression of the BRCA2-associated DUB, USP11, was found to down-regulate ERα transcriptional activity (both in the presence and absence of E2), as demonstrated by a pronounced decrease in estrogen-response element (ERE) luciferase reporter activity. Subsequent validation of the screen using multiple individual hairpins and ZR-75-1 stable USP11 knockdown cells confirmed the suppression of ERE-reporter activity and further revealed a notable reduction in expression of the endogenous ER target genes TFF1 and PgR following USP11 knockdown. In vitro phenotypic analysis also revealed a global decrease in cell survival, decreased ERK and AKT phosphorylation and increased sensitivity to DNA-damaging agents in USP11 knockdown cell lines compared to non-targeting controls.
In silico analysis of publically available breast cancer gene expression datasets revealed a highly significant association between high USP11 mRNA levels and poor prognosis. We observed a highly significant correlation between high expression of USP11 mRNA in ER positive patients and poor overall survival (OS)(HR 1.51, CI 1.07-2.14, p=0.018) and distant metastasis-free survival (DMFS)(HR 1.35, CI 1.04-1.73, p=0.023). This correlation was also significant in ER positive patients who had received endocrine therapy (OS, HR 3.4, CI 1.2-9.81, p=0.014), DMFS, HR 2.16, CI 1.23-3.8, p=0.0083). These results suggest a role for USP11 in driving cellular growth and identify USP11 as a rationale and novel therapeutic target in breast cancer.
Citation Format: Darran P O'Connor, Lisa Dwane, Aisling E O'Connor, Annette M Dirac, Rene Bernards, William M Gallagher. Functional genomic screening identifies USP11 as a novel therapeutic target in 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 P6-03-02.