bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-12-10: Tamoxifen versus anastrozole as adjuvant therapy in early stage breast cancer in premenopausal women on ovarian function suppression: A meta-analysis of randomized clinical trials
Authors: Sidahmed Shima , Abdalla Ahmed , Kheiri Babikir , Bachuwa Ghassan 
Published: March 2020

Abstract
Introduction: Different strategies have been studied in adjuvant treatment for hormone positive early stage breast cancer. The addition of ovarian function suppression (OFS) therapy to Tamoxifen in premenopausal women was proven to prolong disease-free survival and overall survival compared with Tamoxifen alone. However, trials that examined the use of anastrozole inhibitor (AI) in the presence of OFS in comparison to Tamoxifen with OFS showed contradicting results. Therefore, we conducted this meta-analysis of randomized clinical trials (RCTs) comparing these two approaches. Methods: A comprehensive search of the electronic database (PubMed) from inception to July 2019 was conducted to identify all RCTs that compared OFS with Tamoxifen versus OFS with AI in premenopausal females with breast cancer. The primary endpoint was event-free survival, defined as females without events (local or distant recurrence, cancer in the contralateral breast, secondary non-breast malignancy, or death) at the longest follow-up duration. The secondary endpoints were death, the incidence of distant metastasis, and the incidence of contralateral breast cancer. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for all dichotomous data. Heterogeneity was explored by the Cochran Q statistic and I-squared (I2) statistic. P-values &lt;0.05 were considered statistically significant. Results: We included 4 RCTs with 7,202 total patients (mean age 43.8). At baseline, T1 disease represented 53.5% and nodal positive disease was 44.5%. After a median follow-up period of 78 months, there was a non-significant reduction of event-free survival with the AI group compared with the Tamoxifen group (OR=1.13; 95% CI=0.87-1.47; P=0.37). In addition, there were no significant differences between both groups with regard to deaths (OR=1.11; 95% CI=0.50-2.47; P=0.8). The incidence of distant metastasis did not differ between both groups (OR=1.02; 95% CI=0.82-1.26; P=0.86). Similarly, there were no differences in the incidence of contralateral breast cancer between both groups (OR=1.30; 95% CI=0.86-1.96; P=0.21). Conclusions: Among premenopausal women with early breast cancer, the use of AI plus OFS versus Tamoxifen plus OFS was not associated with significantly reduced event-free survival. Given the limited number of RCTs and low events, further, adequately powered trials are needed to validate this finding.
Citation Format: Shima Sidahmed, Ahmed Abdalla, Babikir Kheiri, Ghassan Bachuwa. Tamoxifen versus anastrozole as adjuvant therapy in early stage breast cancer in premenopausal women on ovarian function suppression: A meta-analysis of randomized clinical trials [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 P5-12-10.
Abstract P5-14-14: A validated clinical risk prediction model for cardiac toxicity in patients treated with antiHER2 agents
Authors: Advani Pooja P , Cornell Lauren , Li Zhuo , Ray Jordan , Sanchez Catalina , Villanueva Armando , Smith Taryn , Moreno-Aspitia Alvaro 
Published: March 2020

Abstract
Background: Cardiac toxicity (CT) in the form of left ventricular systolic dysfunction is a well-known complication of anti-HER2 therapy. Prior clinical trial data has suggested potential factors associated with increased risk for CT. We sought to develop a clinical risk prediction model from real world patients to better identify patients who may be at higher risk for CT. Methods: Patients treated with anti-HER2 agents at all Mayo Clinic sites from Jan 2008 to July 2015 were reviewed. Patient data including age, race, body mass index, comorbidities, smoking history, baseline ejection fraction (EF), presence of left ventricular hypertrophy (LVH), prior cancer treatments, number of anti-HER2 agents used, and cardiac medication use were recorded. Factors were compared in patients with and without development of CT. Cox regression models were used to identify univariate and multivariate predictors of CT. A risk score was then assigned based on the final multivariable model. Results: 604 patients were included in final analysis. Median follow-up 2.9 yrs; median age: 57 yr; baseline EF: 64%. One yr CT rate was 7%. Independent predictors of CT were age, baseline EF, LVH, and anthracycline use (C index=0.74). Based on model coefficient, scores of 1, 1, 2 and 3 were assigned to age&gt;55, EF &lt;60%, anthracycline exposure and LVH, respectively. Two random samples of 300 patients were created out of the original cohort for internal validation of the risk score model. In each, the risk score was found to be a highly significant predictor for CT with C index of 0.72 {HR 2.13 (95% CI 1.57-2.90), p &lt;0.001} and 0.77 {HR 2.45 (95% CI 1.74-3.44), p &lt;0.001}. Conclusions: Patients with risk factors of older age, lower baseline EF, anthracycline use and LVH are at increased risk for CT when treated with anti-HER2 agents. Using a risk prediction model at therapy initiation may enhance identification of patients who benefit from cardiology referral, closer cardiac monitoring, and/or prophylactic treatment while on anti-HER2 targeted therapy.
Table 1. Multivariable Cox regression model predicting cardiac dysfunctionParameterParameter EstimateHR (95%CI)p valueScoreAge &gt;550.909552.48(1.27, 4.84)0.00751EF&lt;600.634361.89(1.01, 3.53)0.04751Anthracycline Exposure1.046132.85(1.48, 5.46)0.00162Baseline LVH1.633565.12(2.04,12.85)&lt;0.0013
Citation Format: Pooja P Advani, Lauren Cornell, Zhuo Li, Jordan Ray, Catalina Sanchez, Armando Villanueva, Taryn Smith, Alvaro Moreno-Aspitia. A validated clinical risk prediction model for cardiac toxicity in patients treated with antiHER2 agents [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 P5-14-14.
Abstract P6-02-05: Clumped vs non-clumped internal enhancement patterns in linear non-mass enhancement on breast MRI
Authors: Chen Shu-Tian , Covelli James , Okamoto Satoko , Daniel Bruce , DeMartini Wendy , Ikeda Debra 
Published: March 2020

Abstract
Purpose To compare positive predictive values (PPVs) of clumped versus non-clumped (homogenous and heterogenous) internal enhancement on MRI detected linear non-mass enhancement (NME) on MRI-guided vacuum assisted breast biopsy (MRI-VABB). Materials and Methods With IRB approval, radiology reports were retrospectively reviewed of 598 lesions undergoing 9-gauge MRI-VABB from January 2015 to April 2018 for lesions showing linear NME, recording clumped and non-clumped internal enhancement. We reviewed the electronic medical records for MRI-guided VABB pathology, any follow up surgery and imaging and/or clinical follow-up &gt;1 year (mean 1.7 years). The X2 test was performed for univariate analysis. Results There were 120/598 (20%) linear NME MRI-VABB lesions with clumped (52/120, 43%) vs non-clumped (68/120, 57%) internal enhancement, average size 1.8 cm (range 0.3-7.6 cm). On MRI-VABB, cancer was identified in 22/120 (18%) lesions, ductal carcinoma in situ (DCIS) was found in 18/22 (82%) and invasive cancer (3 IDC, 1 ILC) in 4 (18%). 31/120 (26%) were high-risk lesions with 3/31 (10%) high-risk lesions upgraded to DCIS at surgery, which comprising a total of 25/120 (21%) malignancies. Malignancy was found in 12/52 (23%) clumped lesions and in 13/68 (19%) of non-clumped lesions that showed heterogenous (5/13, 38%) or homogenous (8/13, 62%) internal enhancement. The PPV of linear NME with clumped internal enhancement (23.1%; 95% CI, 11.6-34.6) was not significantly different from the PPV of non-clumped linear NME (19.1%; 95% CI, 9.8-28.4) (p=0.597). The PPV of linear NME lesions &lt;1cm (33.3%; 95% CI, 11.5-55.1) was not significantly different from the PPV of lesions ≥1cm (18.6%; 95% CI, 11.1-26.2) (p=0.157). 53/120 (44%) NME lesions were operated upon. Of the remaining 67 NME not operated upon, 2 benign findings were lost to follow up, and 65 (64 benign, 1 high-risk) showed no suspicious imaging and/or clinical features on follow up. Conclusion Linear NME showed malignancy in 21% of our series. Linear NME with clumped or non-clumped internal enhancement patterns, regardless of lesion size, should undergo MRI-VABB in appropriate clinical settings.
Citation Format: Shu-Tian Chen, James Covelli, Satoko Okamoto, Bruce Daniel, Wendy DeMartini, Debra Ikeda. Clumped vs non-clumped internal enhancement patterns in linear non-mass enhancement on breast MRI [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 P6-02-05.
Abstract P6-03-07: NOTCH3 targeting inhibits ALDH1 activity and restores chemosensitivity in metastatic TNBC
Authors: D'Assoro Antonino Bonaventura 
Published: March 2020

Abstract
Background: Onset of metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which include dissemination of cancer cells from the primary tumor to secondary organs. NOTCH signaling plays a critical role in promoting Triple Negative Breast Cancer (TNBC) metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive.
Methods: We established unique TNBC cells (TNBC-M14, -M25 and -M40), isolated from patient-derived brain metastasis xenografts (PD-BMXs). NOTCH3 genetic targeting was achieved using Lenti-vector shRNAs. Immunoblot analysis was used to assess NOTCH3 expression. ALDH1 activity was established using the ALDEOFLUOR Kit. To assess self-renewal capacity and resistance to docetaxel-based chemotherapy, TNBC cells were cultured under non-adherent conditions to form mammospheres (MPS). A publicly clinical database (http://kmplot.com) was employed to analyze NOTCH3 expression in a selected cohort of 107 lymph- node+ TNBC patients.
Results: TNBC-M14, -M25 and -M40 MPS showed NOTCH3 overexpression and higher ALDH1 activity compared to MDA-MB 231 MPS used as control. To investigate the causative role of NOTCH3 in inducing ALDH1 activity, self-renewal capacity and chemoresistance, we infected TNBC MPS with Lenti-vector shRNAs targeting NOTCH3. NOTCH3 geneting targeting induced a significant reduction of ALDH1 activity compared to TNBC MPS infected with scrambled Lenti-shRNAs. Significantly, NOTCH3 geneting targeting significantly impaired MPS formation and restored sensitivity to docetaxel. The correlation between aberrant NOTCH3 expression and poor outcome in patients with advanced TNBC was also investigated in a publicly clinical database.
Conclusions: These findings provide a compelling preclinical rationale for the design of novel clinical trials that will selectively target NOTCH3 to delay metastatic growth and to improve the clinical outcome of patients with advanced TNBC.
Citation Format: Antonino Bonaventura D'Assoro. NOTCH3 targeting inhibits ALDH1 activity and restores chemosensitivity in metastatic TNBC [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 P6-03-07.
Abstract P6-03-16: Role of autophagy in CD24-mediated TNBC drug resistance
Authors: Huo Lihong , Deng Xinyu , Huang Xiang , Chang Helena R 
Published: March 2020

Abstract
Background: Triple-negative breast cancer (TNBC) is defined by lack of estrogen and progesterone receptors and absence of HER2 amplification. Compared with other breast cancer subtypes, TNBC is more aggressive with more frequent metastasis especially involving visceral and central nervous system. Currently, the only available standard adjuvant treatment is chemotherapy. However, mortality rate remains high despite chemotherapy. To improve treatment, it is crucial to develop novel strategies to predict and overcome drug resistance. Our pervious study showed that CD44/CD24 expressions were associated with drug sensitivity and CD44+/CD24+ TNBC was shown to be resistant to docetaxel. In this study, we aimed to investigate the regulatory mechanism involved in CD24-mediated taxane resistance in TNBC.
Methods: In this study, we used flow cytometry to determine the CD24 expressions in 7 TNBC cell lines. Western blot was used to demonstrate the levels of CD24 and LC3B-II (a marker for cellular autophagy activity) expressions in TNBC cell lines. CD24 expressions in TNBC cell lines were manipulated by target-specific shRNA and gene overexpression approaches. Cell apoptosis assay was used to determine docetaxel drug sensitivity in cells with manipulated CD24 expression. Using the same assay, autophagy inhibitors were used to further evaluate the involvement of autophagy in CD24-mediated drug resistance. To investigate the possible regulatory mechanism, autophagy related signaling pathway Akt/mTOR was studied in CD24 modified TNBC cells.
Results: In this study, the relationship between CD24 expression and autophagy activities in TNBC was evaluated. LC3B-II protein expression was used to determinate autophagy activities. We have shown that TNBC cell lines with high CD24 expressions are associated with increased LC3B-II expression. Suppression of autophagy in CD24 high TNBC cells improves drug sensitivities toward docetaxel. We further demonstrated that knocking down CD24 in TNBC cells suppressed LC3B-II expression and improved docetaxel sensitivity. In addition, gene overexpression of CD24was found to enhance docetaxel resistance in TNBC cells. Our study has also shown that docetaxel increases the activation of Akt/mTOR signaling pathway in drug-resistant TNBC cells. Knocking down CD24 increased Akt/mTOR activation, and decreased the expression of PP2A and LC3B-II in TNBC.
Conclusions: CD24 expression is associated with docetaxel sensitivity and autophagy activity in TNBC cells. Drug sensitivity of CD44+CD24+/high TNBC cells is regulated through autophagy related signaling pathway. Taken together, CD24 mediated TNBC drug resistance is at least partially through autophagy activity.
Citation Format: Lihong Huo, Xinyu Deng, Xiang Huang, Helena R Chang. Role of autophagy in CD24-mediated TNBC drug resistance [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 P6-03-16.
Abstract P6-04-20: Proteogenomic analysis of estrogen modulated breast cancer metastasis
Authors: Chen Anran , Singh Purba , Kim Beom-Jun , Dobrolecki Lacey E , Welm Alana L , Lewis Michael T , Ellis Matthew J 
Published: March 2020

Abstract
Background: Estrogen Receptor (ER) positive breast cancer is the most common subtype (70%) and associated with the most deaths from the disease. Almost all deaths from breast cancer are caused by metastasis. While metastatic ER-positive breast cancer is a leading cause of cancer-related death, metastasis studies have largely focused on ER-negative breast cancer. A major reason for such imbalance is the lack of physiologically relevant mice models for studying ER-positive breast cancer. The patient derived xenograft (PDX) technique provides us with a powerful means to study highly clinically relevant human ER-positive breast cancer in mice, but most studies using PDX models still focus on orthotopic rather than metastatic tumor growth. Here we describe studies of the metastatic process using PDX models to more comprehensively understand the value of these PDX lines for therapeutic modelling. These findings will empower us to develop therapeutics designed to control systemic disease, not just orthotopic tumor growth.
Experimental design and methods: We have studied 14 ER positive PDX lines in ovariectomized SCID beige mice with and without estradiol supplementation. We have analyzed both orthotopic tumor and a variety of metastatic sites including liver, lung, brain and bone. Data is being generated using next-generation DNA and RNA sequencing, mass spectrometry-based proteomics. We use integrated bioinformatics pipelines to shed light on the metastatic process.
Results: We have generated macro-metastatic maps that record sites with observable metastatic nodules of each PDX line in mice. IHC of Liver, bone, brain, lung of each mouse also generated micro-metastatic maps. The most common organ of metastasis in mice is the lung. In some PDX lines, the sites of metastasis differ between groups with and without estradiol supply. The ongoing proteogenomic profiling of orthotopic and metastatic tumors reveals potential molecular drivers of metastasis in ER+ breast cancer.
Conclusion: Here, we describe an approach to the systematic investigation of the ER+ breast cancer metastasis process. This approach will allow us to identify druggable targets that may interrupt the metastatic process and/or inhibit tumor growth at metastatic sites.
Citation Format: Anran Chen, Purba Singh, Beom-Jun Kim, Lacey E Dobrolecki, Alana L Welm, Michael T Lewis, Matthew J Ellis. Proteogenomic analysis of estrogen modulated breast cancer metastasis [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 P6-04-20.
Abstract P6-06-16: Resveratrol enhanced chemosensitivity by reversing macrophage polarization in breast cancer
Authors: Cheuk Isabella Wai Yin , Chen Jiawei , Siu Man Ting , Lam Sau Wing , Wang Jue , Shin Vivian Yvonne , Kwong Ava 
Published: March 2020

Abstract
Background: Resveratrol is a naturally occurring polyphenolic compound in Polygonum cuspidatum and is well known for its antitumor effect by targeting several cancer-related inflammatory pathways. However, limited data is available on the effect of resveratrol in the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant leukocyte population within the tumors and are associated with poor prognosis in over 80% of breast cancer cases. This study aimed to investigate the effect of resveratrol on TAM polarization in breast cancer progression.
Methods: The antitumor effect of resveratrol was examined in MDA-MB-231(MB231), cisplatin resistance MDA-MB-231 (cisR) cells, and T47D by cell proliferation assay using MTT. Gene expressions of M1 and M2 markers in macrophages derived from THP-1 cells were examined by qPCR and immunofluorescence staining after treated with tumor-conditioned medium (TCM) with or without resveratrol (25μM). Cytokine profile of TCM was examined by Qiagen Multi-Analyte ELISArray and expression of cytokines in TCM was validated by qPCR and ELISA. The effect of resveratrol and its downstream targets on macrophage polarization were investigated by supplementing resveratrol with interferon gamma (IFN-γ, 20ng/ml) and lipopolysaccharide (LPS, 100ng/ml) for M1 macrophage polarization or IL-4 (20ng/ml) and IL-13 (20ng/ml)for M2 macrophage polarization. NOD/SCID mice were used to investigate the potential use of resveratrol in treating breast cancer and chemotherapy as complementary treatment in vivo.
Results: Our preliminary data demonstrated that resveratrol significantly reduced cell proliferation and enhanced chemosensitivity in MB231, cisR, and T47D cells. Resveratrol inhibited CD163 (M2 marker) and increased CXCL10 (M1 marker) expression. In addition, resveratrol decreased exogenous IL-6 levels in TCM, thus inhibited breast cancer cell proliferation by promoting M1/M2 macrophage polarization ratio and supressing IL-6/pSTAT3 pathway. Combined use of resveratrol and cisplatin significantly decreased tumor size in vivo.
Conclusion: Our data demonstrated that resveratrol enhanced chemosensitivity in vivo and in vitro by promoting M1/M2 macrophage polarization ratio and supressing STAT3 activation through reducing exogenous IL-6 levels. This study revealed a novel mechanism on resveratrol-mediated macrophage polarization on breast cancer progression.
Correspondence: akwong@asiabreastregistry.com
Citation Format: Isabella Wai Yin Cheuk, Jiawei Chen, Man Ting Siu, Sau Wing Lam, Jue Wang, Vivian Yvonne Shin, Ava Kwong. Resveratrol enhanced chemosensitivity by reversing macrophage polarization in 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 P6-06-16.
Abstract P6-08-14: Assessing the effectiveness of the NCCN genetic testing guidelines in identifying African American breast cancer patients with deleterious genetic mutations
Authors: Ademuyiwa Foluso O , Salyer Patricia , Ma Yinjiao , Fisher Sherri , Colditz Graham , Weilbaecher Katherine , Bierut Laura J 
Published: March 2020

Abstract
Purpose: Approximately 10% of breast cancers are hereditary. Identifying women at high risk for hereditary breast and ovarian cancer allows for early detection, prevention, and individualized disease management for those diagnosed with breast cancer. There is limited data about breast cancer genetic risks among African Americans (AA) as the majority of the large studies have been conducted in European Americans. We examined the distribution of deleterious genetic mutations in AA breast cancer patients, and evaluated the effectiveness of the National Comprehensive Cancer Network (NCCN) guidelines for identifying AA women at high risk for deleterious genetic mutations. Methods: AA participants with breast cancer underwent an interview regarding health and family history, and a 30-gene saliva test. Medical records were accessed to determine whether participants had received prior genetic testing as part of usual care, results of previous testing, and cancer characteristics. Results: Two hundred and fifty participants were enrolled between February 2016 and May 2018. Twenty (8.0%) had a deleterious mutation in one of the 30 genes; BRCA2 had the highest frequency (40.0%). 187 (74.8%) met eligibility for testing based on NCCN guidelines. Only 110 (58.8%) of participants eligible for genetic testing, according to guidelines, had received prior testing as part of routine care. Using the 30-gene test, we identified deleterious mutations in 17 of 187 (9.1%) of those who met NCCN criteria for testing, and three of 63 (4.8%) of those who did not meet criteria for testing nonetheless had a deleterious mutation associated with breast cancer. Conclusions: Our results indicate that a large proportion of African American breast cancer patients who meet criteria for genetic testing do not receive it as part of routine care. Even in women who do not meet testing guidelines, nearly 5% have a known deleterious mutation associated with breast cancer.
Citation Format: Foluso O Ademuyiwa, Patricia Salyer, Yinjiao Ma, Sherri Fisher, Graham Colditz, Katherine Weilbaecher, Laura J Bierut. Assessing the effectiveness of the NCCN genetic testing guidelines in identifying African American breast cancer patients with deleterious genetic mutations [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 P6-08-14.