bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-04-21: Analysis of serum immune biomarkers for response to therapeutic personalized peptide vaccination in patients with metastatic breast cancer
Authors: Toh Uhi , Saku Shuko , Takao Yuko , Sakurai Sayaka , Takenaka Miki , Shichijo Shigeki , Itoh Kyogo , Akagi Yoshito 
Published: March 2020

Abstract
Purpose: Our results from the previous clinical trials using personalized peptide vaccines (PPV) combined conventional chemo-hormonal therapies have confirmed the potential for clinical benefit in patients who had higher IgG antibody and/or CTL response to the immunized PPV (SABCS 2018 U Toh etc.). The aim of this study is to evaluate the association between the serum immunologic factors including cytokines, haptoglobin (HP), B-cell activating factor (BAFF) etc. and the clinical outcome of patients(pt) with metastatic breast cancer (mBC) who treated by personalized peptide vaccines (PPV). Methods: Peripheral blood samples from 57 pts and 52 pts obtained before and after the vaccination of PPV, respectively. Serum HP and IL-6 were analyzed by ELISA(R&D Systems, Life Technologies)and bead-based multiplex assays(Luminex 200 system)were performed for GM-CSF,IFN-γ,TNF-α, BAFF, TGF-β, IFNγ-induced protein 10(IP-10), IL-1β, IL-2,-4,-5,-8, -10. The association between each factor and clinical outcome was statistically evaluated. Results: Pt’s group (n=28) with low BAFF and high HP level (&gt;544 pg/ml), high IFN-γ and high HP level or low IL-8 and high HP level before PPV treatment showed a significantly shorter median survival time (MST; p=0.015;0.068;0.002, respectively). There was no difference in high BAFF, low IFN-γ or high IL-8 level group(n=29). In contrast, pt’s group with low serum level of IL-10, GM-CSF, IL-5, IL-4 and low HP level (&lt;544 pg/ml MV) after PPV treatment associated with significantly shorter MST (p=0.002; 0.001; 0.001; &lt;0.001, respectively). Conclusions: The combination of serum levels of HP and BAFF, IFN-γ or cytokines of IL-8, -10, - 5, -4 might be useful prognostic biomarkers for mBC pts receiving PPV therapy.
Citation Format: Uhi Toh, Shuko Saku, Yuko Takao, Sayaka Sakurai, Miki Takenaka, Shigeki Shichijo, Kyogo Itoh, Yoshito Akagi. Analysis of serum immune biomarkers for response to therapeutic personalized peptide vaccination in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-21.
Abstract P5-05-09: Chemo-sensitization of triple negative breast cancer by targeting RNA-binding protein HuR
Authors: Wu Xiaoqing , Wei Lanjing , Gardashova Gulhumay , Zhong Cuncong , Lan Lan , Zhang Qi , Dixon Dan A , Welch Danny R , Aubé Jeffrey , Xu Liang 
Published: March 2020

Abstract
Triple negative breast cancer (TNBC) has a lower 5-year survival rate and higher recurrence rate compared to other types of breast cancer, which is partially due to the acquired resistance to current treatment regimens. The RNA-binding protein Hu antigen R (HuR) is overexpressed in breast cancer. Cytoplasmic HuR accumulation correlates with high-grade malignancy, poor distant disease-free survival and serves as a prognostic factor for poor clinical outcome in breast cancer. HuR promotes tumorigenesis by promoting mRNA stability and translation of proteins implicated in proliferation, survival, angiogenesis, invasion, and metastasis. HuR also modulates sensitivity of breast cancer cells to chemotherapy. HuR knockout in TNBC cells with high HuR sensitizes them to chemotherapy while HuR overexpression induces chemo-resistance. Meanwhile, chemotherapy promotes cytoplasmic HuR accumulation and increases expression of HuR target encoding proteins in TNBC cells. Therefore, there is a positive feedback loop between HuR and chemo-resistance. These findings suggest that HuR plays a critical role in promoting a drug-resistance mechanism and HuR is a potential target for developing a novel therapy to overcome chemo-resistance in TNBC. RNA-binding proteins such as HuR had previously been considered to be “undruggable” due to the lack of a well-defined binding pocket for target RNAs. Nevertheless, using high throughput screening followed by structure-based rational design and lead optimization, we have identified small molecules that potently inhibit HuR-mRNA interaction with nM to sub-µM potency. Our top HuR inhibitor, KH-3, inhibits TNBC cell growth in vitro and in vivo. KH-3 also sensitizes TNBC cells to docetaxel and doxorubicin treatment in vitro. Furthermore, acquired docetaxel-resistant MDA-MB-231 cells and doxorubicin-resistant MDA-MB-231 cells display similar sensitivity to KH-3 to their parental cells. In the study of mechanism of action, several HuR direct targets are found to be involved in acquired docetaxel and doxorubicin resistance. KH-3 can disrupt the interaction of HuR with those target mRNAs. In animal efficacy studies, the combination of KH-3 and chemotherapy shows synergistic effect in both parental and acquired resistant cell xenograft models. Our data provide a proof-of-principle that HuR inhibition by KH-3 may be developed as a promising molecular therapy to overcome chemo-resistance of TNBC with high HuR.
Citation Format: Xiaoqing Wu, Lanjing Wei, Gulhumay Gardashova, Cuncong Zhong, Lan Lan, Qi Zhang, Dan A Dixon, Danny R Welch, Jeffrey Aubé, Liang Xu. Chemo-sensitization of triple negative breast cancer by targeting RNA-binding protein HuR [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-09.
Abstract P5-05-11: Novel small molecule STAT3 inhibitors induce apoptosis and suppress cell migration and tumor growth in triple-negative breast cancer cells
Authors: Pan Li , Chen Xiang , Fu Shengling , Li Chenglong , Lo Hui-Wen , Lin Jiayuh 
Published: March 2020

Abstract
Persistent STAT3 signaling is frequently detected in many cancer types and thus could potentially serve as a viable therapeutic target. In this study, we tested two novel small STAT3 inhibitors, LLY17 and LLL12B in triple-negative breast cancer cells, which frequently express persistent STAT3 phosphorylation. LLY17 and LLL12B selectively inhibited IL-6-mediated induction of STAT3 phosphorylation but no effect on IFN-γ mediated induction of STAT1 phosphorylation. LLY17 and LLL12B induced apoptosis in triple-negative breast cancer cells but exhibited minimal toxicity toward normal mammary epithelial cells. RNAi attenuation experiments confirmed the requirement of STAT3 for LLY17 and LLL12B-mediated inhibition of cell viability in triple-negative breast cancer cells. LLY17 and LLL12B inhibited STAT3 phosphorylation in human and murine triple-negative breast cancer cells. In addition, LLY17 and LLL12B inhibited cell migration of human and murine triple-negative breast cancer cells. Furthermore, LLY17 and LLL12B suppressed tumor growth and STAT3 phosphorylation of triple-negative breast cancer cells in vivo in a mammary fat pad murine syngeneic mouse model. Together, our findings suggest that targeting persistent STAT3 signaling pathway by novel oral bioavailable small molecules LLY17 and LLL12B may be a potential approach for the therapy of triple-negative breast cancer.
Citation Format: Li Pan, Xiang Chen, Shengling Fu, Chenglong Li, Hui-Wen Lo, Jiayuh Lin. Novel small molecule STAT3 inhibitors induce apoptosis and suppress cell migration and tumor growth in triple-negative breast cancer cells [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-11.
Abstract P5-05-13: Inhibition of NOTCH signaing with g-secretase inhibitor AL101 contributes to overcome resistance against HER2-targeted therapy in HER2 amplified breast cancer cells
Authors: Nakad Bothaina , Broner Esther Channah , Sidransky David , Izumchenko Evgeny 
Published: March 2020

Abstract
Notch signaling affects multiple cellular processes including stem cell maintenance, differentiation, proliferation, motility and survival. Activated NOTCH signaling and up-regulation of tumor-promoting NOTCH target genes are well documented in human breast cancer. Growing evidence suggest the novel role of NOTCH pathway as a survival resistance mechanism against HER2-targeted therapy in the HER2 amplified breast cancer subgroup, accounting for 20% of breast cancers. It was reported that tumor cells that develop intrinsic or acquired resistance to HER2 targeted therapy (at either relapse of the dormant resistant cells or at the progression of HER2 disease), express higher levels of NOTCH pathway genes. The small molecule AL101 is an γ-secretase inhibitor that potently inhibits the activation of all 4 NOTCH receptors (NOTCH1-4). We hypothesize that treatment with AL101, could potentially block activation of this intrinsic resistance mechanism and/or inhibit the acquisition of the acquired resistance. The goal of this study is: (a) to test the efficacy of first line treatment of anti-HER2 drugs combined with AL101, and (b) to test the efficacy of the AL101 as a second line therapy for anti-HER2 resistance breast cancer cells lines. Our study demonstrates the potential utility of HER2-targeted therapy in combination with AL101 as a novel strategy for overcoming the NOTCH signaling induced survival resistance mechanism in HER2 amplified breast cancer cells, and suggests NOTCH inhibitors as potential second-line therapy for recurrent or resistant HER2 amplified breast cancer tumors.
Citation Format: Bothaina Nakad, Esther Channah Broner, David Sidransky, Evgeny Izumchenko. Inhibition of NOTCH signaing with g-secretase inhibitor AL101 contributes to overcome resistance against HER2-targeted therapy in HER2 amplified breast cancer cells [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-13.
Abstract P5-05-16: Quantitative regression of estrogen receptor alpha positive breast cancer
Authors: Boudreau Matthew W , Hergenrother Paul J , Duraki Darjan , Wang Lawrence , Mao Chengjian , Park Ben H , Fan Tim M , Nelson Eric R , Shapiro David J , Moreno Ramon , Bruckheimer Elizabeth , Kiefer Jeffrey , Tarasow Theodore M 
Published: March 2020

Abstract
Treatment of advanced ERα-positive breast cancer remains a major clinical challenge, as the standard therapeutics are mostly cytostatic agents, ultimately leading to drug resistance. Resistant ERα-positive tumors typically retain ERα expression, suggesting an opportunity to develop new therapeutics that move beyond inhibition of this nuclear receptor. Through a medicinal chemistry campaign, we have discovered an estrogen receptor selective activator, the compound ErSO, that – in stark contrast to current ERα modulators – potently kills ERα-positive breast cancer cells. ErSO is effective even against breast cancer cell lines with known mutations in ERα that confer drug resistance. ErSO hyperactivates the anticipatory unfolded protein response, leading to quantitative cell death. ErSO is well-tolerated in mice, orally bioavailable, blood-brain-barrier penetrant. Using sensitive tumor imaging, ErSO often leads to quantitative tumor eradication (without recurrence) in multiple mouse models of ERα-positive breast cancer, including those utilizing breast cancer cell lines harboring mutant ERα. This potent activity against advanced primary and metastatic ERα-positive breast cancers represents a paradigm shift in leveraging of ERα for anticancer efficacy.
Citation Format: Matthew W Boudreau, Paul J Hergenrother, Darjan Duraki, Lawrence Wang, Chengjian Mao, Ben H Park, Tim M Fan, Eric R Nelson, David J Shapiro, Ramon Moreno, Elizabeth Bruckheimer, Jeffrey Kiefer, Theodore M Tarasow. Quantitative regression of estrogen receptor alpha positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-16.
Abstract P5-08-08: Risk reducing mastectomy in average and high risk patients with locally advanced triple negative breast cancer
Authors: Stjepanovic Neda , Giffoni Danilo , Gandhi Sonal , Jerzak Katarzyna , Lemon Sharon , Ott Karen , Pezo Rossanna , Pritchard Kathleen , Tabbarah Samuel , Trudeau Maureen , Warner Ellen , Tran William , Eisen Andrea 
Published: March 2020

Abstract
Background: Women with locally advanced triple negative breast cancer (LA-TNBC) have a high risk of disease recurrence and are monitored clinically and with annual mammograms. High risk women, such as BRCA1/2 carriers, are additionally monitored for second primary breast cancers (BC) with annual MRIs and may opt for risk reducing mastectomy (RRM) as a prophylactic measure. Our aim was to explore the clinical outcomes of patients (pts) with average BC risk and high BC risk (known BRCA1/2 carriers) who undergo RRM at the time of LA-TNBC diagnosis.
Methods: We included 78 consecutive LA-TNBC pts, stages IIB and III, with resectable unilateral disease, treated at the Sunnybrook Health Sciences Centre from 2009 to 2018. Pts who did not undergo systemic chemotherapy and surgical treatment were excluded, as well as pts with a history of prior BC. Medical records were reviewed for clinical outcomes, pathology and germline BRCA1/2 testing results. Log rank test was used to determine the time to recurrence (TTR) and overall survival (OS) differences among women who underwent RRM and those who did not.
Results: Median age at diagnosis of LA-TNBC was 49 years (range 27-82) and 14 (18%) pts were BRCA1/2 carriers. All pts underwent neoadjuvant chemotherapy with 27 (35%) presenting complete pathological response. Fifteen pts underwent RRM, out of which seven were BRCA1/2 carriers. Mean follow up time was 34 (2-86) months, during which 25 pts (32%) were diagnosed with distant disease recurrence and none with second primary BC. Median TTR was 10 months (range 1-48) and median OS was 18 months (range 2-86). RRM was not associated with TTR (p=0.45) and OS (p=0.98). Presence of germline BRCA1/2 also did not correlate with TTR (p=0.16) and OS (p=0.21).
Conclusions: In our cohort of pts with LA-TNBC, the prognosis was driven by the risk of recurrence rather than the risk of second primary BCs. RRM was not associated with improved clinical outcomes, regardless the BRCA1/2 status and larger studies are required to support this procedure at the time of diagnosis of LA-TNBC.
Citation Format: Neda Stjepanovic, Danilo Giffoni, Sonal Gandhi, Katarzyna Jerzak, Sharon Lemon, Karen Ott, Rossanna Pezo, Kathleen Pritchard, Samuel Tabbarah, Maureen Trudeau, Ellen Warner, William Tran, Andrea Eisen. Risk reducing mastectomy in average and high risk patients with locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-08.
Abstract P5-08-22: Associations between MYC alterations and clinical pathological characteristics in Chinese patients and TCGA cohort
Authors: Cao Li , Zhang Guochun , Wang Yulei , Chen Bo , Ren Chongyang , Wen Lingzhu , Guo Liping , Li Kai , Jia Minghan , Liao Ning 
Published: March 2020

Abstract
Background MYC is frequently amplified and its amplification is associated with poor prognosis in breast cancer patients. This study aimed to determine the prevalence of MYC alterations from Chinese patients, the correlations between MYC amplification and clinicopathological characteristics, as well as its impacts on patient outcomes in breast cancer patients.
Methods We analyzed 412 cases of breast cancer specimens in Guangdong Provincial People's Hospital (GDPH) for MYC alterations from June 1, 2017 to September 27, 2018, using next generation sequencing. The associations between MYC amplification and clinicopathological characteristics were determined using chi square. We further compared the our results with those from The Cancer Genome Atlas (TCGA) cohort (n=1079). Kaplan-Meier curves were drawn to determine the impacts of MYC amplification on patient outcomes.
Results MYC was amplified in 12.44% (51/410) in GDPH cohort and the mean copy number of our cohort was 4.42 (2.84-11.27), while the frequency of MYC amplification in TCGA cohort was much higher (21.22%, 229/1079). Except that, we also found two fusions. Among these, one was RTFDC1-MYC fusion (AF=1.62%) and the other was PVT1-MYC fusion (AF=3.33%). The case with PVT1-MYC fusion was also found to have PVT1-MYC co-amplification concurrently. In TCGA cohort, we found MYC amplification to be associated with age (P=0.047), tumor type (P=0.000), ER status (P=0.000), PR status (P=0.000), HER2 status (P=0.008) and molecular subtype (P=0.000). Whereas, except for molecular subtype (P=0.028), we only found MYC amplification to be associated with tumor size (P=0.023) and Ki-67 (P=0.031) in GDPH cohort. According to the survival information from TCGA, patients with MYC amplification had significantly inferior overall survival (OS) in both triple negative breast cancer (TNBC) (P=0.02) and HR+/HER2+ breast cancer patients (P=0.03).
Conclusions This study evaluated the differences of MYC mutations in Chinese and and TCGA cohort breast cancer patients. Except for MYC amplification, we found two rare fusions. Results showed MYC amplified less frequently in Chinese patients and was associated with inferior OS in both TNBC and HR+/HER2+ breast cancer patients. We suggest further research with expand the sample size is necessary to draw the ethnical differences of MYC mutations.
Citation Format: Li Cao, Guochun Zhang, Yulei Wang, Bo Chen, Chongyang Ren, Lingzhu Wen, Liping Guo, Kai Li, Minghan Jia, Ning Liao. Associations between MYC alterations and clinical pathological characteristics in Chinese patients and TCGA cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-22.
Abstract P5-08-24: Impaired glucose tolerance decreases mammographic breast density in Japanese women
Authors: Uchida Ken , Kitano Naruki , Yamaguchi Daisuke , Nogi Hiroko , Kamio Makiko , Takeyama Hiroshi 
Published: March 2020

Abstract
Background; Many studies have demonstrated an association between diabetes and breast cancer risk. Purpose; We examined whether fasting glucose and hemoglobin A1c (HbA1c) are associated with mammographic breast density in Japanese women. Methods; Study consisted of 6,203 women who attend breast cancer screening with the medical health check-up (2014-2019). We used mammographic breast density assessed at the first breast screening. Fasting serum glucose and HbA1c were examined at the same day on the breast cancer screening. The association between breast density and fasting serum glucose and HbA1c were analyzed by logistic regression adjusted for potential confounding factors. Serum glucose and HbA1c levels were calculated with continuous variables. BI-RADS c and d were defined as dense breast tissue. Results; Of 6,203 women with mean age of 51 years, dense breast tissue was present in 60.0 % of participants. 960 (15.1%) had hyper-glycemia (≥100) and 2,830 (45.62%) had hyper-HbA1c (&gt;5.5%). As table 1 illustrates, hyper-glycemia and hyper-HbA1c were significantly inversely associated with dense breast tissue, (serum glucose: odds ratio; 0.987 confidence interval: 0.982-0.992, p&lt;0.01, HbA1c: odds ratio; 0.699, confidence interval:0.614-0.796, p&lt;0.01). There was no effect modification of these associations by menopausal status, body mass index (BMI) and other confounding factors. Conclusions; Hyper-glycemia and hyper-HbA1c are associated with a decrease in mammographic breast density in Japanese women.
Table 1 The relations of glucose intolerance and mammographic breast density.odds ratioconfidence intervalp valueFasting serum glucose0.9870.982-0.992&lt;0.01HbA1c0.6990.614-0.796&lt;0.01
Citation Format: Ken Uchida, Naruki Kitano, Daisuke Yamaguchi, Hiroko Nogi, Makiko Kamio, Hiroshi Takeyama. Impaired glucose tolerance decreases mammographic breast density in Japanese women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-24.
Abstract P5-12-12: Prospective evaluation of adherence to adjuvant aromatase inhibitor (AI) therapy among Hispanic/Latino women with breast cancer (BC) living in the border city of El Paso, Texas
Authors: Philipovskiy Alexander , Campbell Aleli , Castillo Brenda , Heydarian Rosalinda , Gaur Sumit , Dwivedi Alok , Nahleh Zeina 
Published: March 2020

Abstract
Background: Adjuvant therapy with AI improve survival and is recommended to all postmenopausal women with hormone receptor-positive BC. A typical duration of the therapy is from 5 to 10 years. Despite clinically proven efficacy early discontinuation rate approaching 10% per year. The purpose of this study was to determine the adherence level through the Morisky Medication Adherence Scale (MMAS-8) among women with breast cancer treated at Texas Tech University Health Sciences Center El Paso (TTUHSC EP). Methods: Institutional review board approval was obtained prior to initiating this prospective study. 133 postmenopausal women were consented and participated in this study. Patients seen at the TTUHSC EP who was diagnosed with stage I-III breast cancer and who were on adjuvant AIs, were given the MMAS-8 questionnaire, and a demographics questionnaire. In order to identify reasons for non-adherence to AIs, all patients were also asked to identify the reason why they did not take their medication if applicable.Results: One hundred thirty-three patients were enrolled, median age 64 (range 41 - 89), 110 (90.2%) identified themselves as Hispanic/Latino. 58.2% have an income of 15K or less. 39% completed eighth grade or less, 34.5% completed high school, and 12% obtained a technical degree. Mean duration of AI therapy was 6.5 years. The majority of patients have high or intermediate levels of adherence 88%. Only 12 % had a low level of adherence. 7 (5.6%) patients scored two or below in the intentional adherence scale, and 18 (13.5%) scored two or below in the unintentional adherence scale (maximum scale is four). Conclusions: Our results indicate that the majority of patients treated at TTUHSC EP have a high or intermediate level of adherence to AI therapy. The main reason listed for non-adherence were mostly unintentional: forgetfulness and missing getting refills on time.
Citation Format: Alexander Philipovskiy, Aleli Campbell, Brenda Castillo, Rosalinda Heydarian, Sumit Gaur, Alok Dwivedi, Zeina Nahleh. Prospective evaluation of adherence to adjuvant aromatase inhibitor (AI) therapy among Hispanic/Latino women with breast cancer (BC) living in the border city of El Paso, Texas [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-12.