bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-04-15: Ethinylestradiol treatment downregulates ER and upregulates PgR; Immunohistochemical analysis in postmenopausal breast cancer tissues after prior long-term estrogen-deprivation therapy
Authors: Iwase Hirotaka , Omoto Yoko , Takeshita Takashi , Yamamoto-Ibusuki Mutsuko , Hayashi Mitsuhiro , Sueta Aiko , Fujiwara Saori , Yamamoto Yutaka 
Published: May 2015

Abstract
Background: Estrogen receptor (ER) positive breast cancer can often be treated by hormone therapy; however a certain population of ER-positive patients becomes resistant to hormone therapy after long-term hormone treatment. Ethinylestradiol (EE2) is a derivative of estrogen which has shown promising effects on in these patients. Methods: We successfully obtained tissue samples from 6 patients undergoing EE2 treatment and examined 13 well-known breast cancer-related factors by analyzing their gene expression and by immunohistochemistry. Of the 6 patients, 5 responded but one patient did not.
Results: Before EE2 treatment, staining for both ER and androgen receptor (AR) was strong in the nucleus, with weak staining of the progesterone receptor (PgR). EE2 treatment significantly down-regulated ER and up-regulated PgR while nuclear and cytosolic AR were oppositely down- and up-regulated, respectively, by EE2. Cytosolic staining of BRCA1 was significantly up-regulated by EE2 whereas nuclear staining tended to decrease. Individual comparisons suggested less induction of PgR and decreasing AKT but increasing pAKT in the non-responder following EE2 treatment. Conclusion: Our observations revealed that EE2 activated ER downstream genes, although it did not stimulate cell growth. This suggests that hormone resistant cells might receive growth signals from a non-genomic pathway and this may be reflected in their sensitivity to EE2 treatment.
Citation Format: Hirotaka Iwase, Yoko Omoto, Takashi Takeshita, Mutsuko Yamamoto-Ibusuki, Mitsuhiro Hayashi, Aiko Sueta, Saori Fujiwara, Yutaka Yamamoto. Ethinylestradiol treatment downregulates ER and upregulates PgR; Immunohistochemical analysis in postmenopausal breast cancer tissues after prior long-term estrogen-deprivation therapy [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 P3-04-15.
Abstract P3-04-16: Estrogen receptor β agonists reduce breast cancer tumor growth in syngeneic mouse models
Authors: Samayoa Cathy , Krishnegowda Naveen K , Vadlamudi Ratna K , Tekmal Rajeshwar R 
Published: May 2015

Abstract
The estrogen receptors (ER) play a significant role in breast cancer, with the majority of breast cancers expressing estrogen receptor alpha (ERα) and depending on its signaling. ERα has proliferative function, however, estrogen receptor beta (ERβ) has anti-proliferative functions. Recently, several selective ERβ agonists have been identified. The objective of this study was to determine the effectiveness of ERβ agonists in inhibiting the growth of distinct breast cancer cells both in-vitro and in-vivo, and to determine the mechanisms involved. The mouse mammary tumor cell lines, D2A1 and MM51, express both ERα and ERβ. Specifically D2A1 cells are dependent on estrogen for growth and have increased expression of aromatase. Additionally, D2A1 cells are very aggressive and highly metastatic; representing a good model of breast cancer progression. MM51 cells are Her2/neu positive and are an adequate model to study the crosstalk between growth factors and ER signaling. Syngeneic mouse tumor models were used to incorporate an intact immune system which plays a role in the tumor’s microenvironment. Our in-vitro studies demonstrate that ERβ agonists significantly inhibit cell growth in a dose dependent manner. Our syngeneic studies show that, in-vivo, ERβ agonists effectively reduce tumor volume and inhibit tumor progression. This study reveals that in addition to acting on ERβ, these agonists reduce the expression of ERα at both the mRNA and protein level, therefore modulating the ratio of ERα to ERβ. Additionally, treatment with ERβ agonists results in increases apoptosis through increased p53 expression, and cell cycle arrest through p27 and cyclin D1. Together, these studies demonstrate the therapeutic potential of ERβ agonists for the treatment of breast cancer.
Citation Format: Cathy Samayoa, Naveen K Krishnegowda, Ratna K Vadlamudi, Rajeshwar R Tekmal. Estrogen receptor β agonists reduce breast cancer tumor growth in syngeneic mouse models [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 P3-04-16.
Abstract P3-05-11: Glutamine metabolism promotes survival through the unfolded protein response in endocrine resistant breast cancer
Authors: Shajahan-Haq Ayeasha N , Demo Susan , Clarke Robert 
Published: May 2015

Abstract
About 70% of all breast cancers are estrogen receptor alpha positive (ER+). Anti-hormone therapy such as antiestrogens (e.g.,Tamoxifen; TAM) are often used to treat ER+ breast cancer but breast cancer cells can develop resistance to these drugs (endocrine resistance). Unfortunately, ∼50% percent of all antiestrogen treated tumors eventually develop endocrine resistance, and therefore, there is an urgent need to find ways to treat this incurable disease. Endocrine resistant cells survive antiestrogen treatment by initiating a pro-survival pathway mediated by an evolutionary conserved process call the unfolded protein response (UPR) within the endoplasmic reticulum. Cellular stress induced by therapeutics can be initiated by the UPR leading to a pro-survival response in the short-term and a pro-death response in the long-term, depending on the magnitude of the stress signal. Our studies show that antiestrogens can decrease glucose uptake in ER+ breast cancer cells, and in glucose-deprived conditions, presence of glutamine in the media can trigger the UPR through GRP78-IRE1a. Subsequently, a glutamine-dependent pathway can induce cell death via GRP78-IREa-JNK-CHOP and survival in others via GRP78-IRE1a-XBP1. Glutamine metabolites such as glutamate (essential substrate for many vital cellular processes) and proline (substrate for collagen production) are significantly elevated in endocrine resistant cells. Knockdown of glutaminase (GLS1) with siRNA or small molecule inhibitor, CB-839, significantly decreased cell proliferation in endocrine resistant cells compared with sensitive cells within 48 h. Moreover, cell lines derived from endocrine resistant cells that are grown in glucose-free media are significantly more sensitive to CB-839 compared with their respective controls, indicating an increased dependency on glutamine. Glutamine may offer an alternate source of energy and raw materials in periods of glucose deprivation, and in endocrine resistant cells, this adaptive pro-survival cellular metabolic mechanism is up-regulated. Thus, CB-839 may be a potent anti-cancer agent in treating antiestrogen resistant breast cancers.
Citation Format: Ayeasha N Shajahan-Haq, Susan Demo, Robert Clarke. Glutamine metabolism promotes survival through the unfolded protein response in endocrine resistant 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 P3-05-11.
Abstract P3-05-23: Novel, non-uterotrophic, selective estrogen mimics cause regression of tamoxifen-resistant breast cancer in 2D and 3D cultures and in mouse xenograft models
Authors: Thatcher Gregory RJ , Xiong Rui , Patel Hitisha K , Zhao Jiong , Liang Xiao , Wang Yue-ting , Molloy Mary Ellen , Tonetti Debra 
Published: May 2015

Abstract
Prior to the advent of tamoxifen therapy, estradiol (E2) and the ER agonist, diethylstilbestrol, showed efficacy in the clinical in therapeutic treatment of breast cancer. The adverse effects of these therapeutic options led to discontinuation, despite tamoxifen itself sharing the adverse effect of uterine growth. The perceived therapeutic action of tamoxifen in countering the proliferative actions of E2 at the estrogen receptor (ER) in endocrine-sensitive breast tissues is not entirely compatible with the therapeutic actions of E2 itself in breast cancer, and points to a more complex role for ER. Tamoxifen is the standard of care for many patients with ER+ breast cancer; however significantly, 30-50% of women are resistant to tamoxifen therapy. Development of a Selective Estrogen Mimic (SEM) that is effective in breast cancer without uterotrophic and other side effects is a novel treatment option that we hypothesize will be effective in causing regression of tamoxifen-resistant breast cancer. We theorize that a rational approach would be an ER ligand with pharmacological partial agonist actions, thus able to mimic E2 in regressing breast cancer, but with antagonist actions in the face of excessive ER activation. Using the benzothiophene scaffold common to the clinical Selective Estrogen Receptor Modulators (SERMs), raloxifene and arzoxifene, we hypothesized that an ideal SEM could be designed by structural engineering. A library of over 30 compounds was developed and assayed in tamoxifen-resistant cell lines, including MCF-7 and T47D. One SEM was assayed in two mouse xenograft models and shown to cause tumor regression; impressively this SEM did not fuel growth of estrogen-dependent T47D xenografts and did not cause uterine growth. This SEM and several other compounds were observed to act as partial agonists at ERα, with variable actions at ERβ. To understand this phenomenon further, the contributions of apoptotic mechanisms and cell cycle arrest to SEM activity was studied in cell cultures. The results collected to date on SEMs that act as partial agonists at ERα indicate that this is a viable, new approach to breast cancer therapy.
Citation Format: Gregory RJ Thatcher, Rui Xiong, Hitisha K Patel, Jiong Zhao, Xiao Liang, Yue-ting Wang, Mary Ellen Molloy, Debra Tonetti. Novel, non-uterotrophic, selective estrogen mimics cause regression of tamoxifen-resistant breast cancer in 2D and 3D cultures and in mouse xenograft models [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 P3-05-23.
Abstract P3-05-24: Adaptation to AI therapy in breast cancer can induce dynamic alterations in ER activity resulting in estrogen independent metastatic tumours
Authors: Vareslija Damir , McBryan Jean , Fagan Ailis , Redmond Aisling , Hao Yuan , Hill Arnold DK , Young Leonie S 
Published: May 2015

Abstract
Acquired resistance to aromatase inhibitor therapy is a major clinical problem in the treatment of breast cancer. The detailed mechanisms of how tumour cells develop this resistance remain unclear. Here, discovery of pro-survival adaptations to the estrogen receptor (ER) signalling pathway in response to AI treatment is reported. Global ChIPseq analysis shows that the ER retains binding activity in AI resistant cells under steroid-depleted conditions. In AI treated patients, evidence of steroid independent adaptive ER signalling was demonstrated by the ER target gene Early Growth Response 3 (EGR3). Expression of EGR3 decreased initially upon AI treatment but subsequently recovered following as little as 12 weeks of AI treatment. In vitro data indicates that this increased expression of EGR3 may enhance cell growth and motility of tumour cells. Finally, evidence from established metastatic tumours suggests that the ER signalling network may undergo further adaptations with disease progression as EGR3 expression is routinely lost in the established metastatic tumour. Overall, these data provide evidence of a dynamic ER response to AI treatment which may provide vital clues for overcoming the clinical issue of AI resistance.
Citation Format: Damir Vareslija, Jean McBryan, Ailis Fagan, Aisling Redmond, Yuan Hao, Arnold DK Hill, Leonie S Young. Adaptation to AI therapy in breast cancer can induce dynamic alterations in ER activity resulting in estrogen independent metastatic tumours [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 P3-05-24.
Abstract P3-07-19: Breast cancer risk perception and adherence to U.S. cancer prevention guidelines
Authors: Hofstatter Erin , Chagpar Anees 
Published: May 2015

Abstract
Introduction: In the United States, nearly 200,000 cancer-related deaths each year are attributed to poor diet and physical inactivity. We sought to determine whether perceived personal breast cancer risk was associated with adherence to healthy lifestyle habits in a nationally representative sample.
Methods: The National Health Interview Survey (NHIS) is a population-based survey conducted each year by the CDC, designed to represent the non-institutionalized civilian population in the United States. We utilized data from the 2010 NHIS adult and cancer supplements to compare fruit/vegetable intake, alcohol use and exercise habits among women who perceived themselves to be at high risk of developing breast cancer versus those women who perceived themselves to be at average or low risk.
Results: In 2010, 12,055 women without a history of cancer were surveyed, representing 94,990,140 people in the population. Perceived risk of breast cancer was not associated with improved adherence to nutrition and physical activity guidelines (see Table). Less than 5% of all U.S. women meet the recommended fruit/vegetable intake regardless of perceived risk, and only one-third of all women achieve recommended physical activity. Approximately 95% of women adhere to guidelines regarding alcohol intake. On multivariate analysis, perceived risk did not affect health habits when controlling for age, ethnicity, education, insurance status, income, region and body mass index (BMI).
Conclusion: Thousands of breast cancer diagnoses and deaths could be prevented each year through healthy diet and exercise. Yet, a striking majority of U.S. women do not adhere to cancer prevention recommendations, including those women who perceive themselves to be at high risk of breast cancer. These findings suggest that patient education and awareness of personal breast cancer risk may be essential, but not sufficient, for motivating meaningful behavior change.
Univariate AnalysisMultivariate AnalysisPerceived High Risk-% meeting guidelinesPerceived Low/Avg Risk-% meeting guidelinesp-valueOR (95% CI)p-valueFruit/Veg Intake (&gt;=5 svg daily)4.90%4.42%0.56791.14 (0.78-1.66)0.5110Alcohol Intake (&lt;=7 svg/wk)94.22%95.13%0.30930.84 (0.61-1.17)0.3076Physical Activity (75-150 min vig-mod act/wk)30.11%27.74%0.14651.02 (0.87-1.21)0.7921
Citation Format: Erin Hofstatter, Anees Chagpar. Breast cancer risk perception and adherence to U.S. cancer prevention guidelines [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 P3-07-19.
Abstract P3-08-04: Aspirin and breast cancer risk for BRCA1 and BRCA2 mutation carriers
Authors: Kornhauser Naomi , Terry Mary Beth , Vahdat Linda T , Andrulis Irene , Buys Saundra , Daly Mary , John Esther , Hopper John L , Cigler Tessa 
Published: May 2015

Abstract
Background : Although epidemiologic studies have found evidence that aspirin use may be inversely associated with breast cancer (BC) risk, little is known about whether this applies to BRCA1 and BRCA2 mutation carriers.
Methods : We compared aspirin use in 613 women with BRCA1 or BRCA2 mutations from the six centers of the Breast Cancer Family Registry (BCFR) who were recruited at baseline and completed a questionnaire at 10 year follow-up. We defined cases as carriers with BC (n = 215 with BRCA1 mutations and 137 with BRCA2 mutations) and controls as carriers unaffected with BC (n = 141 with BRCA1 mutations and 120 with BRCA2 mutations). We used logistic regression to estimate odds ratios and 95% confidence intervals separately by gene mutation type.
Results : Three cases (1.4%) and 27 controls (19.1%) among the BRCA1 carriers and 3 cases (2.2%) and 25 controls (20.8%) among the BRCA2 carriers reported ever use of aspirin-based medications before diagnosis. Aspirin use before diagnosis was inversely associated with BC risk for both BRCA1 (OR, 0.13; 95% CI, 0.04-0.46 for ever vs. never use) and BRCA2 (OR, 0.12; 95% CI, 0.03-0.41 for ever vs. never use) carriers, after adjusting for age and center for BRCA1 carriers and age for BRCA2 carriers.
Conclusion : If replicated by larger, prospective studies, aspirin use could become an inexpensive and acceptable risk-reducing measure for BRCA1 and BRCA2 mutation carriers.
Citation Format: Naomi Kornhauser, Mary Beth Terry, Linda T Vahdat, Irene Andrulis, Saundra Buys, Mary Daly, Esther John, John L Hopper, Tessa Cigler. Aspirin and breast cancer risk for BRCA1 and BRCA2 mutation carriers [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 P3-08-04.
Abstract P3-11-09: Elevated peripheral blood lymphocyte-to-monocyte ratio predicts favorable response and prognosis in locally advanced breast cancer after neoadjuvant chemotherapy
Authors: Wang Lei , Ni Xiao-Jian , Qian Guo-Wei , Ou-Yang Qian-Wen , Zhang Xiao-Lan , Jiang Yi-Zhou , Chen Sheng , Hu Xin , Shao Zhi-Ming 
Published: May 2015

Abstract
Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced breast cancer (LABC). However, the lack of efficient method to predict the treatment response and prognosis limits the clinical evaluation of the patient eligibility. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies and nasopharyngeal carcinoma, but has not been studied in breast cancer. The purpose of this study is to evaluate whether the LMR is a predictor of the curative impact of LABC patients after NAC and short/long-term mortality. A retrospective cohort of 542 LABC patients who received NAC was recruited between May 2002 and August 2011. The counts for peripheral absolute lymphocyte and monocyte before NAC were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate Cox proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS) and disease-free survival (DFS) respectively. Univariate analysis revealed that higher LMR level (≥4.25) was significantly related to better overall response rate (P = 0.005). Univariate analysis revealed that higher LMR level (≥4.25) was significantly associated with superior OS (P = 0.014), DFS (P = 0.009). The higher lymphocyte count (≥1.5×109/L) was significantly associated with better OS (P = 0.035), while the lower monocyte count (&lt;0.4×109/L) was associated with better OS (P = 0.007) and DFS (P = 0.01), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR = 0.636, 95% confidence interval or 95% CI = 0.432-0.937; P = 0.022), DFS (HR = 0.666, 95% CI = 0.495-0.896; P = 0.007) respectively. The traditional predictive factors, including tumor size, lymph node status, hormone receptor status and HER2 status, were also independent prognostic factors of OS and DFS. The elevated pre-NAC peripheral LMR level was a significant favorable factor for NAC LABC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of LABC patients after NAC.
Citation Format: Lei Wang, Xiao-Jian Ni, Guo-Wei Qian, Qian-Wen Ou-Yang, Xiao-Lan Zhang, Yi-Zhou Jiang, Sheng Chen, Xin Hu, Zhi-Ming Shao. Elevated peripheral blood lymphocyte-to-monocyte ratio predicts favorable response and prognosis in locally advanced breast cancer after neoadjuvant chemotherapy [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 P3-11-09.
Abstract P3-13-10: The maintenance treatment after xeloda contained regimens with xeloda or endocrine for HR positive and HER2 negative MBC patients
Authors: Jiang Zefei , Qi Fan , Zhang Shaohua , Bian Li , Wang Tao , Li Lei 
Published: May 2015

Abstract
Objective To discuss the optimizing selection of maintenance treatment after xeloda-contained chemotherapy regimen being applicated in HER-2 negative, HR positive relapsing metastatic breast cancer(MBC) patients, and contrast the curative effect of maintenance treatment with xeloda or endocrine. Methods 119 patients with HER-2 negative, HR positive were enrolled during 2009-2013.All patients taking the xeloda contained chemotherapy regimens to obtain CR,PR or SD were randomly divided into group A(65 cases, maintenance capecitabine therapy 800-1000mg/ m2 bid, orally, Days 1 ∼ 14, q3w)and group B(54 cases, a switch to maintenance endocrine therapy). Endpoints include overall survival (OS) and progression-free survival (PFS). Results The ages, menopausal status, number of metastases and treatment line numbers had no statistical differences between two groups, and the p value of two therapy co-operative groups was 0.002. There were 37 patients(56.9%)using TX and 28(43.1%)using NX in therapy co-operative group A. There were 39 patients (72.2%)using TX, 9(16.7%)using NX and 6(6%) using regimen containing xeloda in therapy co-operative group B. Progression-free survival was 8 months in patients who follow by xeloda and 12 months in those who follow by endocrine (p&lt;0.01).Conclusion Endocrine therapy after xeloda-contained chemotherapy regimen tend to be more effective than single xeloda therapy for patients with HER-2 negative, HR positive. This results request to be verified by advanced OS data, which was needed to in-depth study in clinic and explore relevant biological indicators.
Citation Format: Zefei Jiang, Fan Qi, Shaohua Zhang, Li Bian, Tao Wang, Lei Li. The maintenance treatment after xeloda contained regimens with xeloda or endocrine for HR positive and HER2 negative MBC patients [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 P3-13-10.