bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PS10-30: An open label, pilot study of veliparib and lapatinib in patients with metastatic, triple negative breast cancer
Authors: Stringer-Reasor Erica M , May Jori E , Olariu Eva , Caterinicchia Valeria , Li Yufeng , Manna Deborah Della , Rocque Gabrielle B , Vaklavas Christos , Falkson Carla I , Nabell Lisle M , Acosta Edward P , Forero-Torres Andres , Yang Eddy S 
Published: February 2021

Abstract
Purpose: Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2(gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple negative breast cancer (TNBC) with intact DNA repair, we previously showed an induced synthetic lethality with combined EGFR inhibition and PARPi. We report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC. Experimental Design: A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline and taxane therapy. Patients with gBRCA1/2 mutations were excluded. Results: Twenty patients were enrolled of which 17 were evaluable for response. Median number of prior therapies in the metastatic setting was 1 (range 0-2). Fifty percent of patients were Caucasian, 45% African-American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug-drug interactions noted. Gene expression analysis suggest baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders. Conclusions: Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed.
Citation Format: Erica M Stringer-Reasor, Jori E May, Eva Olariu, Valeria Caterinicchia, Yufeng Li, Deborah Della Manna, Gabrielle B Rocque, Christos Vaklavas, Carla I Falkson, Lisle M Nabell, Edward P Acosta, Andres Forero-Torres, Eddy S Yang. An open label, pilot study of veliparib and lapatinib in patients with metastatic, triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-30.
Abstract PS11-01: Outcome without adjuvant systemic treatment in breast cancer patients included in the MINDACT trial
Authors: Cardozo Josephine MN Lopes , Byng Danalyn , Drukker Caroline A , Schmidt Marjanka K , van 't Veer Laura J , Cardoso Fatima , Piccart Martine , Poncet Coralie , Rutgers Emiel JTh 
Published: February 2021

Abstract
Background: Adjuvant systemic treatments have played an important role in the decline of breast cancer mortality over the years. Because of the extensive short- and long-term toxicities associated with these treatments, careful selection of patients likely to benefit from them is needed. Studies have shown excellent survival in subgroups of patients receiving no adjuvant systemic treatments. Some national guidelines advise no adjuvant systemic treatments in specific groups of patients with clinical low risk breast cancer. The aim of this study is to investigate the survival of breast cancer patients who received no adjuvant treatment (chemotherapy nor endocrine therapy) using data from the EORTC 10041/BIG 3-04 MINDACT trial. Material and methods: Of the 6693 patients enrolled in the MINDACT trial, accrued 2007-2011, 509 patients with hormone receptor positive, HER2 negative, lymph node negative tumors &lt;2cm received no adjuvant systemic treatment, mostly following local recommendations. Median follow-up was 8.7 years. Using propensity score matching and exact matching, we will identify groups of patients treated with adjuvant endocrine therapy and/or chemotherapy with similar tumor characteristics to the untreated patients. We will use the Kaplan-Meier method to estimate distant metastasis free interval and overall survival at 5 and 8 years for each group. Differences between groups will be evaluated using the log-rank test, and hazard ratios with 95% CI derived from Cox proportional hazards models. Planned analyses: The long-term data of the MINDACT trial has recently become available. The date of planned analysis is August 10th 2020.For this study, the primary clinical endpoint will be distant metastasis free interval, which will be assessed in the matched groups of untreated patients, patients who received endocrine therapy only, and patients who received chemotherapy with or without endocrine therapy. Kaplan-Meier estimates will be provided at 5 years, and at 8 years to assess the long-term outcomes in this population. A statistical plan for this analysis was specifically developed and approved prior to performing any analysis.
Citation Format: Josephine MN Lopes Cardozo, Danalyn Byng, Caroline A Drukker, Marjanka K Schmidt, Laura J van 't Veer, Fatima Cardoso, Martine Piccart, Coralie Poncet, Emiel JTh Rutgers. Outcome without adjuvant systemic treatment in breast cancer patients included in the MINDACT trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-01.
Abstract PS12-11: Phase 1b clinical trial of HX008, a novel anti-PD-1 monoclonal antibody, Combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer
Authors: Hu Xichun , Cao Jun , Wang Biyun , Zhang Jian , Wang Leiping , Tao Zhonghua , Li Ting 
Published: February 2021

Abstract
Background HX008 is a humanized IgG4S228P anti-PD-1 monoclonal antibody with an engineered Fc domain. Gemcitabine plus cisplatin (GP) has shown satisfying antitumor activity as first-line therapy for metastatic triple-negative breast cancer (mTNBC) in CBCSG 006 trial (ClinicalTrials.gov, NCT01287624). The phase 1b study was conducted to assess the safety and preliminary antitumor activity of HX008, combined with GP in patients with mTNBC in first-line setting. Methods Eligible patients are mTNBC with ≥6 months DFI who never receive antitumor therapy for metastatic disease. Participants received HX008 at 3mg/kg (d1, q3w) plus gemcitabine at 1250mg/m2 (d1, 8, q3w) and cisplatin 75mg/m2 (d1, q3w). At most 6 cycles of GP chemotherapy were given, while HX 008 could be maintained until disease progression or unacceptable toxicity occurred. Results Between July 2019 and March 2020, a total of 31 patients were enrolled in this study. Median (range) age was 50 (29-69) years. Among 31 patients who were evaluated, 25 (80.6%) experienced objective response and the other 6 (19.4%) experienced stable disease (SD). The median progression free survival (PFS) was 9.07 months (95%CI,7.29m-13.01m). The PFS data was not yet mature, for nearly half of the intent-to-treat population has not progressed by October 9, 2020. The most common treatment-related adverse events of grade 3 or 4 included neutropenia (71.0%), anemia (55.5%), thrombocytopenia (32.3%), hypocalcemia (9.68%), hypokalemia (6.45%), and Alanine aminotransferase increased (6.45%). There were no treatment-related deaths. Conclusion HX008 plus GP demonstrated promising activity and manageable safety in patients with mTNBC in first-line setting. Clinical trial information: CHINADRUGTRIALS.ORG, CTR 20191353.
Citation Format: Xichun Hu, Jun Cao, Biyun Wang, Jian Zhang, Leiping Wang, Zhonghua Tao, Ting Li. Phase 1b clinical trial of HX008, a novel anti-PD-1 monoclonal antibody, Combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-11.
Abstract PS14-17: Rapamycin inhibits stem cell function and diminishes inflammation and senescence markers in human mammary gland
Authors: Bouamar Hakim , Broome Larry , Gu Xiang , Nazarullah Alia , Brenner Andrew , Kaklamani Virginia , Jatoi Ismail , Sun Lu-Zhe 
Published: February 2021

Abstract
Gene expression profiles of some subtypes of breast cancer were shown to correspond to the profiles of the basal or luminal mammary stem/progenitor cell-enriched epithelial cells implicating the mammary stem cells (MaSCs) as tumor-initiating cells for certain types of breast cancer. Moreover, there is growing evidence that MaSCs may initiate neoplastic transformation when dysregulated in mouse models. We have previously reported an increased frequency of the MaSC-enriched Lin-/CD49fhigh/CD24+ basal cells in old mice (&gt;27 month) compared to young ones (2-4 month) along with an increase of hyperplasic lesions. Gene expression profile revealed an increase of immune and inflammatory responses in old basal cells and stroma cells indicating that aging-induced immune and inflammatory responses might initiate basal cell expansion and transformation. Our preliminary data on mice using rapamycin, an immune and inflammation inhibitor, were very encouraging so we decided to start a clinical window trial (NCT02642094) to test whether rapamycin could reduce biomarkers associated with progression to invasive breast cancer and MaSC numbers in postmenopausal patients with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS). The patients enrolled in the trial took rapamycin (sirolimus, 2mg/day) for 5-7 days with 3-7 days of washout before surgery. The adjacent non-tumor surgical tissues were used for the measurements of sphere formation efficiency (SFE) of the basal and luminal cells. The control group were patients with ADH/DCIS who did not take the drug. Rapamycin treatment significantly diminished the SFE of the basal MaSC. Immunohistochemical staining of the biopsies and surgical tissues showed that rapamycin treatment significantly decreased the levels of COX2 (an inflammation marker) and p16 (a senescence marker), and moderately increased p62 (an autophagy marker). Furthermore, rapamycin significantly reduced the proliferation marker Ki67 staining. In conclusion, rapamycin inhibits MaSCs function and senescence and inflammation features in human mammary glands. Whether the suppression of the senescence-associated inflammatory responses is the mechanism by which rapamycin suppresses MaSC function is under investigation.
Citation Format: Hakim Bouamar, Larry Broome, Xiang Gu, Alia Nazarullah, Andrew Brenner, Virginia Kaklamani, Ismail Jatoi, Lu-Zhe Sun. Rapamycin inhibits stem cell function and diminishes inflammation and senescence markers in human mammary gland [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-17.
Abstract PS14-25: Outcomes of metastatic male breast cancer
Authors: Dogan Izzet , Khanmammadov Nijat , Aydıner Adnan , Saip Pınar 
Published: February 2021

Abstract
Background: Breast cancer is rare in men. The prognosis of male breast cancer (MBC) is poor than female breast cancer. The study aims to evaluate the clinical features and prognosis in metastatic male breast cancer (mMBC).
Method: The data of 28 patients were retrospectively reviewed. The clinical and histopathological features of the patients were recorded. Overall survival (OS) and prognostic factors evaluated with Kaplan-Meier analysis and Cox-regression analysis.
Results: The median follow-up period was 55.1 months (range, 6.6-205.6). The median age at diagnosis was 57 years (range, 26-86). Seven (27%) of the patients were de-novo metastatic. Invasive ductal carcinoma (92.6%) was the most common pathological subtype. The ratio of HER2 positivity in patients was 21.6%, and estrogen and progesterone receptor's positivity were 96.4% and 71.4%, respectively. The most common metastatic locations of disease were bone-75%, lung-39.3%, brain-21.4%, and surrenal-10.7%. Six of the patients received trastuzumab-based chemotherapy. A total of 14 (50%) patients deceased during the study period. The median OS was 42.6±10.7 months (range, 21.6-63.7) for all patients. One-, three- and five-years overall survival ratios were 95.7%, 54.2%, and 36.6%, respectively. In univariate analysis, Brain metastasis (p=0.033), the number of metastatic sites (p=0.045), and the history of regular alcohol consumption (p=0.008) were a statistically significant factor on OS. However, the results were not confirmed in multivariate analysis. Also, we found that trastuzumab-based treatment and de-novo metastasis were not affecting on OS in mMBC.
Conclusions: Due to the rarity, the data of mMBC is limited. In this study, we observed that the prognosis of mMBC was poor. Despite the low number of patients, we detected that having brain metastasis, the number of metastatic sites, and history of alcohol consumption may be a prognostic factor in univariate analysis.
Citation Format: Izzet Dogan, Nijat Khanmammadov, Adnan Aydıner, Pınar Saip. Outcomes of metastatic male breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-25.
Abstract PS14-26: Comparison of clinicopathological features in BRCA-wild type and -mutated male breast cancer patients
Authors: Dogan Izzet , Aydın Esra , Yazıcı Hülya , Saip Pınar 
Published: February 2021

Abstract
Background: BRCA mutations result in a variety of cancer types such as breast, ovarian, and prostate. 4-40% of the patients with male breast cancer have BRCA mutations, and BRCA 2 mutation is more commonly detected. In this study, we compared the clinicopathological characteristics of BRCA- wild type and -mutated male breast cancer (MBC).
Methods: The data of 43 patients were retrospectively reviewed. Clinical and histopathological data of the patients were recorded. The characteristics of the patients were compared by the chi-square test and Fisher exact test. Survival analysis evaluated with Kaplan-Meier analysis.
Results: The median follow-up period was 35.8 months (range, 2.2-225.8). The median age at diagnosis was 58 years (range, 25-81) and not statistically different between groups (p=0.753). 11 (25.6%) of the patients had BRCA mutations. Four (9.3%) patients had BRCA1 mutations, six (14%) patients BRCA2 mutations, and one (2.3%) patients had both BRCA 1 and 2 mutations. Among BRCA- wild type and - mutated patients: estrogen receptor positivity (p=0.055), progesterone receptor positivity (p=0.698), HER2 overexpression (p=0.542), tumor localization (p=0.305), tumor histology (p=0.069), lymph node involvement (p=0.589), tumor stage (p=0.892), and recurrence status (p=0.698) were comparable. The median overall survival was 115.6 months (range, 76.0-155.3), and similar between groups (p=0.647).
Conclusions: MBC is rare. In literature, the data of MBC and BRCA mutation is limited, and studies included a low number of patients. In a result, we found that clinicopathological characteristic and prognosis of BRCA-mutated and-wild type MBC was similar.
Citation Format: Izzet Dogan, Esra Aydın, Hülya Yazıcı, Pınar Saip. Comparison of clinicopathological features in BRCA-wild type and -mutated male breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-26.
Abstract PS14-28: Core−shell structured gold nanorods@iron-based metal-organic framework for magnetic resonance imaging guided photothermal therapy in triple-negative breast cancer
Authors: He Jingchao , Zhang Haijun 
Published: February 2021

Abstract
Background/Objective: As the most aggressive subtype of breast cancer, triple-negative breast cancer (TNBC) with high mortality lacks effective treatment options and results in poor prognosis. Photothermal therapy (PTT) has emerged as a potential anticancer strategy. Until now, the construction of multifunctional photothermal agents is vital importance for effective PTT generally. In this work, the novel core-shell gold nanorods (GNs)@iron-based metal-organic framework (Fe-MOF) was firstly successfully fabricated for magnetic resonance imaging (MRI) guided PTT in TNBC. The inner GNs have excellent photothermal properties and the outer Fe-MOF shell endow the nanocomposite with superior T2 MRI property.Methods: The GNs @ Fe-MOF was firstly prepared by a layer-by-layer technique. Prepared nanocomposite was characterized by measuring measuring measuring transmission electron microscope (TEM), UV-Vis-NIR absorption spectra, powder X-radiffraction (XRD) patterns. MR imaging of nanocomposite was assessed in vitro and in vivo. The biocompatibility and photothermal cytotoxicity of the nanocomposite was assessed by a CCK-8 assay. The photothermal effect of nanocomposite in vivo was evaluated by monitoring tumor growth. The tumor tissues were analyzed by Hema-toxylin and eosin (H&E) to further analyze photothermal effect. The toxicity of the materials in major organs was also investigated by H&E.Result: The core-shell GNs @ Fe-MOF was successfully prepared and displayed excellent dispersion. The nanocomposite possessed good biocompatibility and effectively killed tumor cells under laser irradiation. Meanwhile, the nanocomposite showed clear signal contrast in T2-weighted images in vitro and in vivo. Moreover, the nanocomposite significantly inhibited tumor growth under laser irradiation in vivo. H&E showed that the nanocomposite caused serious damage to tumor tissue under laser irradiation.Conclusion: The current work developed a novel multifunctional core-shell GNs @ Fe-MOF with good biocompatibility for MRI guided PTT in TNBC.Keywords : Magnetic resonance imaging, Photothermal therapy,gold nanorods@iron-based metal-organic Framework
Citation Format: Jingchao He, Haijun Zhang. Core−shell structured gold nanorods@iron-based metal-organic framework for magnetic resonance imaging guided photothermal therapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-28.
Abstract PS16-11: Potential therapeutic effects of HDACi FK228 on TNBC using various models
Authors: Alzoubi Madlin , Nguyen Khoa , Hebert Katherine , Matossian Margarite , Burks Hope , Collins-Burow Bridgette , Burow Matthew 
Published: February 2021

Abstract
Breast cancer is the most prevalent type of cancer among women. Most breast cancers are hormone sensitive, however triple negative breast cancer (TNBC), a more aggressive subtype of breast cancer is characterized by its negative expression of estrogen and progesterone receptors, and lack of Her2/NEU amplification. Because of its receptor status, hormone receptor targeted treatments are ineffective against TNBC making it difficult to treat. FK228, known as Romidepsin, is a histone deacetylase inhibitor (HDACi) that specifically targets the enzymes HDACs 1 and 2, tumor suppressor and other proteins exerting epigenetic changes on tumor cells resulting in anticancer activity. FK228 has not been studied in TNBC, but has been approved by the FDA for the treatment of peripheral T-cell lymphoma (PTCL), where the mechanism of action has demonstrated cell cycle arrest and apoptosis [1,2]. To assess the preliminary role of FK228 in breast cancer, a number of TNBC cell lines were treated with the drug and analyzed for suppression of cell cycle genes. Similar to PTCL, TNBC cell lines showed an increase in cell cycle arrest genes such as p21 and others subsequent to treatment. Moving forward, to recapitulate the tumor microenvironment we have utilized 2D and 3D culture, while PDXs (patient derived xenografts), an excellent translational tool. We first identified changes in morphology and migration in 2k1, MDA-MB 231 and HS-578t cell lines treated with FK228 under in-vitro conditions. Additional molecular studies also show a reversal of the epithelial to mesenchymal transition (EMT) in FK228 treated BC cell lines; specifically in relation to EMT genes CDH1 and ZEB2, both directly connected to HDAC1/2 activity. To further study the effects of FK228, PDXs are implanted into mice to study growth patterns, recurrence, metastatic potential and response to FK228 in different patient tumor models. FK228 showed a drastic suppression in tumorigenesis in model TU-BCX-2O0, prompting the study of several other models in tumorigenesis including TU-BX-4IC, 4M4 and 4QX. Metastasis was also monitored by H&E staining lung and liver tissue for analysis for each model, and using an in vivo model consisting of GFP/luciferase transfected breast cancer cells MDA-MB-231 and SUM-159 to monitor both the proliferation and spread of disease in mice. Ultimately this study aims to characterize the FK228 alteration of pathways involved in tumorigenesis, metastasis and resistance within TNBC.
Citation Format: Madlin Alzoubi, Khoa Nguyen, Katherine Hebert, Margarite Matossian, Hope Burks, Bridgette Collins-Burow, Matthew Burow. Potential therapeutic effects of HDACi FK228 on TNBC using various models [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-11.