bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract OT1-01-01: The NEO-LET-EXE-trial: An intra-patient cross-over trial to explore the "lack of cross-resistance" between steroidal and non-steroidal aromatase inhibitors
Authors: Bahrami N , Sauer T , Loeng M , Gravdehaug B , Engebretsen SS , Aljabri B , Bemanian V , Lindstrøm JC , Lüders T , Kristensen VN , Geisler J 
Published: May 2019

Abstract
Background. The aromatase inhibitor letrozole and the aromatase inactivator exemestane currently belong to the most widely used antihormonal drugs for breast cancer worldwide. Both compounds are strongly suppressing estradiol levels in postmenopausal patients with breast cancer. However, in the metastatic setting, these drugs may be used after another, causing new responses in selected patients following switching to the alternative drug after progressing on the first choice. This well-known “lack of cross resistance” has been recognized for some time and is documented by several trials. However, the precise explanation for this clinical observation is still unknown. The solution may potentially lead us to a novel strategy to treat hormone-sensitive breast cancer.
Trial design. NEO-LET-EXE is a neoadjuvant, randomized, open-label, intra-patient cross-over trial .
Eligibility criteria. Postmenopausal patients suffering from estrogen receptor (ER) positive (&gt;50%), HER-2 negative, locally advanced breast cancer, suitable for neoadjuvant/presurgical antihormonal therapy, may be enrolled. Age: 18+ (no upper limit).
Specific aims. To explain the phenomenon of a lack of cross-resistance between steroidal and non-steroidal aromatase inhibitors in vivo. Sequential tumor biopsies and blood samples, obtained at baseline and following 2 months of therapy with each drug given in sequence, will be used to perform a comprehensive exploration of the consequences of each drug therapy. The influence on plasma and tissue steroids (estrogens, androgens, etc.) will be compared. In addition, whole genome sequencing, whole exome sequencing, epigenetics, proteomics and plasma analysis (cytokines, tumor DNA fragments, etc.) will be performed.
Statistical methods. Data will be analyzed using mixed effects models.
Present accrural and target accrural. 49 out of planned 100 patients have been enrolled so far. The last patient is expected to enter the trial in Q4 2019.
Citation Format: Bahrami N, Sauer T, Loeng M, Gravdehaug B, Engebretsen SS, Aljabri B, Bemanian V, Lindstrøm JC, Lüders T, Kristensen VN, Geisler J. The NEO-LET-EXE-trial: An intra-patient cross-over trial to explore the "lack of cross-resistance" between steroidal and non-steroidal aromatase inhibitors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-01-01.
Abstract OT1-02-01: Phase I trial of bicalutamide and ribociclib in androgen receptor-positive triple negative breast cancer
Authors: Sharifi M , Wisinski KB , Burkard ME , Tevaarwerk AJ , Tamkus D , Chan N , Truica C , Danciu O , Hoskins K , O'Regan RM 
Published: May 2019

Abstract
Background: To date, the use of anti-androgens in the subset of triple negative breast cancers (TNBC) that express androgen receptor (AR) has shown modest response rates, indicating anti-androgen-resistance in the majority of these tumors. Based on data that Cyclin D kinase (CDK) inhibitors reverse resistance to anti-androgens in prostate cancer cell lines, we hypothesize that the use of CDK inhibition may enhance the activity of anti-androgens in AR-positive TNBC.
Methods: Key eligibility include: patients with centrally confirmed AR-positive TNBC, defined as AR expression &gt;0%; 0 to 1 line of prior therapy for metastatic disease; and measurable disease. Patients are treated with bicalutamide 150mg orally once daily plus ribociclib at one of 3 dose levels (see table).
Table 1Dose levelBicalutamideRibociclib1150mg orally once daily (D1 to 28)400mg daily (D1 to 21)2150mg orally once daily (D1 to 28)400mg daily (D1 to 28)3150mg orally once daily (D1 to 28)600mg daily (D1 to 21)
Results: AR expression was positive by trial criteria in 74% of screened patients. Three patients have been accrued at each dose level. Median age is 56 and 6 and 3 patients were treated in first and second-line settings, respectively. Median AR expression was 50% (range 5 to 75%). Toxicity data is available for 6-patients treated on dose levels 1 and 2. No dose-limiting toxicities were noted. As anticipated with ribociclib, the most common toxicity is neutropenia (1 patient grade 4 and 2 patients grade 3). Two patients experienced grade 3 hypertension and 1 experienced grade 3 lymphopenia. Grade 2 or lower toxicities included fatigue, nausea, hyperglycemia and mucositis. One patient experienced grade 1 QT interval prolongation.
Conclusion: The combination of bicalutamide and ribociclib is tolerable without unexpected toxicities. Data on the 3-patients treated at dose level 3 and dose expansion will be included. Phase 2 dosing schedule will be decided based on phase 1 results.
Citation Format: Sharifi M, Wisinski KB, Burkard ME, Tevaarwerk AJ, Tamkus D, Chan N, Truica C, Danciu O, Hoskins K, O'Regan RM. Phase I trial of bicalutamide and ribociclib in androgen receptor-positive triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-02-01.
Abstract OT1-05-03: Efficacy and safety of scalp cooling device for prevention of alopecia in patients with breast cancer
Authors: Kodera A , Ogura K , Hattori A , Yukawa H , Sakaguchi S , Matsuoka A , Tanaka N , Kamimura M , Jibiki N , Naritaka Y , Hirano A 
Published: May 2019

Abstract
Background
Chemotherapy for breast cancer causes alopecia as a side effect. Some patients refuse chemotherapy because of alopecia, resulting in the omission of a standard therapy. It is believed that a scalp cooling device can prevent alopecia by promoting vasoconstriction of the scalp and reducing exposure of the hair root cells to anticancer agents. There are phenotypic differences of the efficacy of a scalp cooling device for alopecia. In fact, a Dutch scalp cooling registry reported that the success rate of scalp cooling was 51% in European women and 33% in Asian women. Therefore, we aimed to investigate the efficacy of scalp cooling device for chemotherapy-induced alopecia among Asian women with breast cancer.
Trial design
This is a phase II trialto evaluate the efficacy and safety of scalp cooling device for risk reduction of alopecia in women with stage I/II/III breast cancer treated with adjuvant/neoadjuvant chemotherapy in a single institute.
Eligibility criteria
Women diagnosed with Stage I to III breast cancer who are scheduled to receive preoperative or postoperative adjuvant chemotherapy containing anthracycline and/or taxanes are enrolled. Patients who have blood malignancies (leukemia, non-Hodgkin lymphoma, other systemic lymphoma), and cold allergy, are excluded.
Specific aims
The primary endpoint is the proportion of patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 0-1 alopecia after the completion of all cycles of chemotherapy (success rate). Secondary endpoints are safety, quality of life, use of wig or cap, and success rates after the completion of all cycles of chemotherapy distinguished by anthracycline(AC) and taxane.
The cooling device is the Paxman scalp cooling system. Scalp cooling was performed from 30 mins before initiation until 90 mins (25 min for taxane) after chemotherapy. Pictures of the scalp were taken at the time of the initiation of each course.
Statistical methods
Successful treatment was defined as the presence of less than 50% of hair-loss area. The sample size was calculated using the Simon method, with a type I error of 10% (two-sided) and a study power of 80%.The expected success rate is 30%, with a threshold success rate of 10%, and the required number of patients was estimated to be 19.
Present and target accrual
Patient accrual was started in April 2018 and present accrual is 3. We plan to enroll a total of 20 patients in the trial.
Citation Format: Kodera A, Ogura K, Hattori A, Yukawa H, Sakaguchi S, Matsuoka A, Tanaka N, Kamimura M, Jibiki N, Naritaka Y, Hirano A. Efficacy and safety of scalp cooling device for prevention of alopecia in patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-05-03.
Abstract OT1-09-01: Phase II trial assessing accuracy of tumor bed biopsies in predicting pathologic response in patients with clinical/radiological complete response after neoadjuvant chemotherapy in order to explore the feasibility of breast-conserving surgery without surgery: NRG Oncology BR005
Authors: Basik M , Costantino JP , De Los Santos JF , Umphrey HR , Julian TB , Mamounas EP , White JR , Lucas PC , Wagner JL , Tjoe JA , Thompson AM , Wolmark N 
Published: May 2019

Abstract
The increased use of neoadjuvant chemotherapy (NCT) has enabled higher rates of breast-conserving surgery (BCS) as well as provided prognostic information for women with breast cancer. High pathological complete response (pCR) rates question the requirement for surgery, with its attendant morbidity. In order to avoid surgery, the ability to predict pCR prior to it must be very high. Trimodality imaging alone is inadequate to predict pCR prior to surgery. We hypothesize that performing core-needle biopsy (bx) of the tumor bed in addition to trimodality imaging in patients (pts) having had a clinical complete response (cCR) will increase the ability to predict pCR. Utilizing predetermined imaging response criteria of complete or near-complete response coupled with a stereotactic core-needle bx of the tumor bed, BR005 aims to determine the predictive value of imaging followed by tumor bed bx for pCR and demonstrate its reproducibility across a multi-institutional setting.
Methods: 175 pts with operable focal or multifocal (T1-T3), stage II/IIIA invasive ductal carcinoma (all receptor subtypes) will be entered. Pts must have completed a minimum of 8 wks of standard NCT and achieved a complete or near-complete radiologic tumor response on breast imaging with mammogram, ultrasound, and MRI, and undergo BCS. Following cCR and prior to surgery, pts will undergo a stereotactic-vacuum-assisted breast bx with clip placement. The primary endpoint is the proportion of pts with post-NCT neg image-directed bx who have a pCR. Residual cancer burden scores and core bx pathology will be collected along with trimodality imaging data. Evaluation after 135 pts will allow for the possibility of early termination of the study. Results will provide the first step toward a paradigm change in the treatment of breast cancer, enabling a study to assess the criteria for successful avoidance of surgery in pts with high response rates to NCT.
Accrual as of 6-15-18: 39 (22.3%).
Support: U10CA180868, -180822, UG1CA189867.
Citation Format: Basik M, Costantino JP, De Los Santos JF, Umphrey HR, Julian TB, Mamounas EP, White JR, Lucas PC, Wagner JL, Tjoe JA, Thompson AM, Wolmark N. Phase II trial assessing accuracy of tumor bed biopsies in predicting pathologic response in patients with clinical/radiological complete response after neoadjuvant chemotherapy in order to explore the feasibility of breast-conserving surgery without surgery: NRG Oncology BR005 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-09-01.
Abstract OT1-12-02: Biomarker study of patients with HER2-negative metastatic breast cancer receiving combination therapy with nivolumab, bevacizumab and paclitaxel as first-line treatment (WJOG9917BTR)
Authors: Ozaki Y , Kitano S , Matsumoto K , Takahashi M , Mukohara T , Futamura M , Masuda N , Tsurutani J , Yoshimura K , Minami H , Takano T 
Published: May 2019

Abstract
Background: In recent years, anti-PD-1 antibody, an immune checkpoint inhibitor, has been developed for the treatment of various types of cancer, including breast cancer. Synergistic effects of nivolumab, paclitaxel and bevacizumab are expected, based on various preclinical data, when these drugs are administered in combination. A biomarker study is ongoing to evaluate the immune status of patients participating in the NEWBEAT trial, which is a phase II trial of nivolumab + paclitaxel + bevacizumab therapy as first-line treatment for patients with metastatic or recurrent HER2-negative breast cancer. Methods: HER2-negative breast cancer patients from the WJOG9917B (NEWBEAT) trial are enrolled in this biomarker study. To explore new biomarkers for combined treatment of breast cancer with immune-checkpoint inhibitors and anti-vascular endothelial growth factor antibodies, we propose to conduct multicolor immunohistochemistry (IHC) assays for immunomonitoring of the intra-tumor environment, such as the expressions of PD-L1, CD4 and CD8. Blood samples are collected before the start of treatment and at four time-points during the treatment, to determine, using a multicolor flow cytometry panel, the numbers of circulating immunosuppressive cells, such as regulatory T cells, myeloid-derived suppressor cells and tumor-associated macrophages (M2). In the NEWBEAT trial, patients receive nivolumab 240 mg/body on days 1 and 15, paclitaxel 90 mg/m2 on days 1, 8 and 15, and bevacizumab 10 mg/kg on days 1 and 15 every 4 weeks until disease progression. The primary endpoint is the objective response rate, and the key secondary endpoints include progression-free survival, overall survival, and toxicity of the protocol treatment. A total of 51 patients will be enrolled and the enrollment period will be one year. This trial opened to accrual in February 2018. Clinical trial registry number: UMIN000029590
Citation Format: Ozaki Y, Kitano S, Matsumoto K, Takahashi M, Mukohara T, Futamura M, Masuda N, Tsurutani J, Yoshimura K, Minami H, Takano T. Biomarker study of patients with HER2-negative metastatic breast cancer receiving combination therapy with nivolumab, bevacizumab and paclitaxel as first-line treatment (WJOG9917BTR) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-12-02.
Abstract OT1-13-02: Molecular testing for minority patients with or at high risk for cancer
Authors: Singh R , Bayan MA , Kadari S , Nganteh MN , Jacksonm M , Woodson LM , Shamsuddin AS , Lemus BY , Pratap S , Murray JJ , Adunyah SE , Lammers PE 
Published: May 2019

Abstract
PURPOSE: Meharry Medical College is a participant in eMERGE (Electronic Medical Records and Genomics); a multicenter network sponsored by NHGRI/NIMHD with the primary goal to develop, disseminate, and apply approaches to research that combine biorepositories with electronic medical records (EMR) for genomic discovery and medicine implementation research. The consortium also focuses on ethical issues involving privacy, confidentiality, and interaction with the broader community. Individual institutions created protocols around research questions individualized to their populations.
METHODS: We enrolled 500 African Americans with or at high-risk for the four most common cancers (prostate, colorectal, breast, lung) to examine possible genetic and proteomic differences to account for health disparities in this population. We will perform DNA, RNA, and proteomics analyses pertinent to these cancers and obtain corresponding clinical history from the EMR with planned long-term follow up.
RESULTS: 500 subjects (211 female) were enrolled over 11 months from Nashville General Hospital including the following cancer/at-risk participants (Breast 59/37; Colorectal 17/128; prostate 31/136; lung 16/76). Most individuals stated that they participated for potential benefit to themselves, family members, or humankind and only 11 percent of potential participants declined. Little concern has been voiced for providing samples for genetic analysis. A genetic counselor will meet with the participants that are found to have pathogenic or likely pathogenic mutations while study investigators will share results with those that are not found to have mutations. Participants will be queried regarding understanding of the genetic testing results and followed for one year to evaluate if they underwent recommended testing and to follow for cancer outcomes.
CONCLUSION: The inclusion of diverse groups in genomic research is critical to identify possible reasons for health disparities and to study the understanding of genetic testing and ethical issues surrounding this topic. In this study, African-Americans are participating willingly in clinical research to examine possible genetic and/or social bases for cancer disparities.
ACKNOWLEDGEMENT: NIMHD (U54MD007593) to the Meharry Translational Research Center (MeTRC); National Human Genome Research Institute (NHGRI); National Institute of Allergy and Infectious Disease (NIAID).
Citation Format: Singh R, Bayan MA, Kadari S, Nganteh MN, Jacksonm M, Woodson LM, Shamsuddin AS, Lemus BY, Pratap S, Murray JJ, Adunyah SE, Lammers PE. Molecular testing for minority patients with or at high risk for cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-13-02.
Abstract OT2-02-01: A confirmation study of omitting axillary dissection in patients with breast cancer and positive sentinel nodes
Authors: Jibiki N , Hirano A , Ochi T , Sakamoto A , Horiuchi K , Noguchi E , Omi Y , Ogura K , Inoue H , Kamio T , Naritaka Y , Fujibayashi M , Hiroshima K , Nagashima Y , Sakai S , Karasawa K , Okamoto T 
Published: May 2019

Abstract
Background
The omission of axillary dissection for positive sentinel-node breast cancer is considered the standard treatment for patients who undergo breast conserving surgery and radiation therapy, according to the results of ACOSOG-Z0011 and AMAROS trials. On the other hand, some surgeons still think that the surgical stress of axillary dissection is minimal, and dissection is permitted. Furthermore, Z0011 contains several problems, such as insufficient number of entry cases and lack of radiation field unity. Thus, we planned a prospective trial to confirm the safety of omitting axillary dissection in patients with breast cancer and positive sentinel nodes.
Trial design
This is a single arm, confirmation study of three medical centers. Prior to surgery, informed consent is obtained, and patients are registered primarily. After surgery, patients with 1 to 2 positive sentinel nodes, for whom axillary dissection was omitted, are finally included in this trial at final registration.
Eligibility criteria
Patients with histologically-diagnosed breast cancer, Tis–2, N0 based on a core needle biopsy, will be included in this trial. Eligible patients must be between 20 and 80 years of age, with a performance status of 0–2 and adequate organ function. They must not have undergone any prior operation, radiation therapy, chemotherapy, endocrine therapy, or immunotherapy.
Specific aims
The primary endpoint is 5-year (y) axillary recurrence rate. Secondary endpoints are 5-y overall survival, 5-y recurrence-free survival, 5-y local recurrence-free survival, the rate of upper-limb lymphedema, quality of life, and comparison of axillary recurrence rates between patients with two or more dissected nodes and those with only one positive node.
Statistical methods
The expected rate of axillary recurrence is 2.0%, and non-inferiority is defined as an axillary recurrence lesser than or equal to 5% in the axillary radiotherapy group. The sample size was calculated with a study power of 80% and type I error of 10% (two-sided). The required number of patients is estimated to be 189.
Present and target accrual
Patient accrual from the three medical centers was initiated in July 2016. We plan to enroll a total of 189 patients at final registration in this trial.
Citation Format: Jibiki N, Hirano A, Ochi T, Sakamoto A, Horiuchi K, Noguchi E, Omi Y, Ogura K, Inoue H, Kamio T, Naritaka Y, Fujibayashi M, Hiroshima K, Nagashima Y, Sakai S, Karasawa K, Okamoto T. A confirmation study of omitting axillary dissection in patients with breast cancer and positive sentinel nodes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-02-01.
Abstract OT2-06-01: Highly innovative personalized RNA-immunotherapy for patients with triple negative breast cancer
Authors: Schmidt M , Bolte S , Frenzel K , Heesen L , Derhovanessian E , Bukur V , Diken M , Gruetzner J , Kreiter S , Klein A , Kuhn A , Langer D , Loewer M , Lindman H , Schneeweiss A , Tuereci O , Sahin U 
Published: May 2019

Abstract
Background: The treatment of triple negative breast cancer (TNBC) is hampered by the lack of established therapeutic targets such as hormone receptors or HER-2. Chemotherapy and radiotherapy is the standard of care, yet survival rates in TNBC remain poor. Approaches tailored to the patient's individual tumor signature may lead to improved therapeutic outcome. We have set up a clinical workflow covering drug development (from target discovery to manufacturing) and drug release providing a custom-made investigational medicinal product (IMP) for each individual patient.
Trial Design: A phase I/II trial assesses the feasibility, safety and biological efficacy of this personalized immunotherapy in three clinical sites in Germany and Sweden. TNBC patients (pT1cN0M0 – TxNxM0) after completion of initial standard of care therapy will be allocated to one of two study arms. Patients in ARM1 receive 8 vaccination cycles with a personalized combination of shared tumor-associated antigens, selected based on each patient tumor's antigen-expression profile out of a WAREHOUSE of pre-manufactured mRNA vaccine. Patients in ARM2 receive the personalized mRNA WAREHOUSE vaccine followed by 8 vaccination cycles of an on-demand manufactured mRNA MUTANOME vaccine encoding up to twenty unique neo-epitopes of the individual patient identified by next generation sequencing. The mRNAs are administered intravenously as a nanoparticulate lipoplex formulation, which protects RNA from degradation, activates innate immunity, transfects APCs and consequently induces highly potent antigen-specific T-cell responses. The treatment of 12 patients in ARM1 is completed and enrolment of patients for ARM2 has started. Preliminary data show that the RNA-WAREHOUSE approach is feasible and can be applied safely. Biomarker analysis is ongoing. This approach is promising as it addresses the heterogeneity of TNBC.
The TNBC-MERIT trial was initially funded by the EU Commission's FP7 and led by BioNTech AG.
Citation Format: Schmidt M, Bolte S, Frenzel K, Heesen L, Derhovanessian E, Bukur V, Diken M, Gruetzner J, Kreiter S, Klein A, Kuhn A, Langer D, Loewer M, Lindman H, Schneeweiss A, Tuereci O, Sahin U. Highly innovative personalized RNA-immunotherapy for patients with triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-06-01.