bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract MS2-3: MS2-3 Clinical implications of DNA repair and genome instability research
Authors: Tutt A 
Published: March 2017

Abstract
Breast cancer has now been subjected to extensive molecular characterisation. Although much attention has focused on transcriptional profiling, with consequent identification of a number of biological sub-types, it is clear that breast cancers show significant variability in their somatic genome. Breast cancers are diseases that are largely dominated by copy number aberrations (CNAs) rather than single nucleotide variants (SNVs). Although HER2 is the poster child CNA driven therapeutic target a number of other mutation and CNA candidates are being pursued. The mutational processes that drive the different forms of genomic instability in breast cancer are increasingly understood and have been described in the last year. These mutational and rearrangement signatures may reveal aberrations in the DNA damage response that themselves represent a vulnerability and a therapeutic target. I will discuss a range of strategies and clinical trials being employed to target DNA repair, genome instability and consequent replicative stress in breast cancer.
I will also discuss the state of development of assays that categorise a range of forms of mutational signature and genome instability which may act in future as predictive biomarkers of therapy response or resistance to DNA damage response targeting therapies with utility in the clinic.
Citation Format: Tutt A. MS2-3 Clinical implications of DNA repair and genome instability research [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr MS2-3.
Abstract OT1-01-02: A phase II trial of neoadjuvant docetaxel/cyclophosphamide followed by epirubicin/cyclophosphamide for triple-negative breast cancer
Authors: Tanaka N , Hirano A , Inoue H , Ogura K , Hattori A , Jibiki N , Yukawa H , Matsuoka A , Kodera A , Kamimura M , Naritaka Y , Shimizu T 
Published: March 2017

Abstract
Background
Currently, an anthracycline followed by a taxane as adjuvant or neoadjuvant chemotherapy is considered the most effective treatment for patients with triple-negative breast cancer. However, docetaxel followed by an anthracycline as neoadjuvant chemotherapy results in a higher rate of pathological complete response (pCR) than the regimen including an anthracycline followed by docetaxel (Iwata et al. Jpn J Clin Oncol 2011). Adjuvant docetaxel/cyclophosphamide (DC) treatment resulted in prolonged survival compared to adjuvant doxorubicin/cyclophosphamide. Therefore, we planned a phase II trial of DC followed by epirubicin/cyclophosphamide (EC) (Trial registration: UMIN000011031).
Trial design
This is a phase II trial to evaluate the efficacy and toxicity of DC followed by EC as neoadjuvant therapy for triple-negative breast cancer. Patients will receive four cycles of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) every 21 days, followed by four cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 21 days.
Eligibility criteria
Patients with histologically diagnosed triple-negative breast cancer, T1–4, N1–3, or T2–T4, N0 based on a core needle biopsy, will be included in this trial. Eligible patients must be between 20 and 70 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 the pCR rate in the breast and axilla, and the secondary endpoints are the breast-conserving rate, toxicities, feasibility, and 5-year overall survival and relapse-free survival. pCR is defined as disappearance of invasive cancer cells, including those in the axilla, although the presence of residual intraductal cancer is acceptable.
Statistical methods
The sample size was calculated using the Simon method, with a type I error of 10% and a study power of 80%. The expected pCR rate is 25%, with a threshold pCR rate of 10%, and the required number of patients has been estimated to be 33.
Present and target accrual
Patient accrual within two medical centers was started in September 2013. We plan to enroll a total of 34 patients in the trial.
Citation Format: Tanaka N, Hirano A, Inoue H, Ogura K, Hattori A, Jibiki N, Yukawa H, Matsuoka A, Kodera A, Kamimura M, Naritaka Y, Shimizu T. A phase II trial of neoadjuvant docetaxel/cyclophosphamide followed by epirubicin/cyclophosphamide for triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-02.
Abstract OT1-02-07: SOPHIA: A phase 3, randomized study of margetuximab plus chemotherapy vs trastuzumab plus chemotherapy in the treatment of patients with HER2+ metastatic breast cancer
Authors: Rugo HS , Pegram MD , Gradishar WJ , Cortes J , Curigliano G , Hong S , Wigginton JM , Lechleider RJ , Cardoso F 
Published: March 2017

Abstract
Background: Despite significant advances in targeted therapy, HER2+ metastatic breast cancer (MBC) remains incurable. Ideal treatment includes pertuzumab and trastuzumab in combination with a taxane in the first line setting, followed by ado-trastuzumab emtansine on progression. Optimal treatment regimens in the third and greater line of therapy are not defined, but continued anti-HER2 therapy is recommended. Margetuximab is a Fc-modified monoclonal antibody to HER2 that recognizes the same epitope on HER2 as does trastuzumab, with similar affinity. Margetuximab demonstrates increased affinity to the activating CD16A Fc-receptor found on NK cells and macrophages and decreased affinity to the inhibitory CD32B receptor compared to trastuzumab. In vitro studies showed enhanced antibody dependent cell-mediated cytotoxicity compared to trastuzumab. In a Phase 1 dose escalation and expansion trial, margetuximab showed single agent clinical activity against HER2+ tumors in patients previously treated with trastuzumab and other anti-HER2 agents. Methods: SOPHIA is a randomized, prospective study testing the hypothesis that margetuximab plus chemotherapy (CTX) is more effective than trastuzumab plus CTX in patients previously treated for HER2+ MBC. Sequential primary endpoints are centrally assessed progression free survival (PFS) and overall survival (OS). The study size of 530 patients is determined to have 80% power to detect a hazard ratio for OS of 0.75. Secondary endpoints are investigator assessed PFS and centrally assessed overall response rate. Eligibility includes prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine; no more than 3 prior lines of therapy in the metastatic setting; prior demonstration of HER2+ status at a local reference laboratory; and absence of active brain metastases. Eligible patients are randomized 1:1 to receive CTX (physician's choice: capecitabine, eribulin, gemcitabine or vinorelbine) plus either margetuximab or trastuzumab until disease progression or toxicity. Antibody may be continued after stopping CTX in patients with responding or stable disease. Progress to date: The trial was initiated July 2015 and is ongoing in the US and Europe with planned expansion to Korea and Israel. ClinicalTrials.gov Identifier NCT02492711; Eudract 2015-000380-13.
Citation Format: Rugo HS, Pegram MD, Gradishar WJ, Cortes J, Curigliano G, Hong S, Wigginton JM, Lechleider RJ, Cardoso F. SOPHIA: A phase 3, randomized study of margetuximab plus chemotherapy vs trastuzumab plus chemotherapy in the treatment of patients with HER2+ metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-02-07.
Abstract OT1-02-09: A phase 2 randomized, double-blinded, controlled study of ONT-380 vs. placebo in combination with capecitabine (C) and trastuzumab (T) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (MBC) (HER2CLIMB)
Authors: Hamilton E , Borges V , Murthy R , Anders C , Cameron D , Carey L , Müller V , Curigliano G , Gelmon K , Hortobagy G , Krop I , Loibl S , Pivort X , Pegram M , Slamon D , Hurvitz S , Tsai M , Winer E 
Published: March 2017

Abstract
Background: ONT-380 is a highly selective small molecule inhibitor of HER2 kinase with nanomolar potency. Unlike dual HER2/EGFR agents, it does not inhibit EGFR at clinically relevant concentrations, decreasing the potential for EGFR-related toxicities (severe skin rash and diarrhea). In preclinical studies, ONT-380 demonstrated synergistic activity with T, and was active in HER2+ models of brain metastases (mets). In a Phase 1b study, ONT-380 was combined with C and T in pts with HER2+ MBC previously treated with trastuzumab emtansine (T-DM1) and T. Objective responses were seen, including in pts with brain mets. The combination was well tolerated, with low rates of Gr 3 diarrhea at the recommended dose (300 mg PO BID, equivalent to the single agent MTD). Based on these data, ONT-380 is now being evaluated in a Phase 2 study in combination with C and T (HER2CLIMB).
Trial Design: The primary study objective is to assess the effect of ONT-380 vs. placebo given with C + T on progression-free survival (PFS) based on independent central review. Additional objectives include ORR, duration of response, clinical benefit rate, and safety. The study population includes adult pts with progressive HER2+ locally advanced or MBC who have had prior treatment with a taxane, T, pertuzumab and T-DM1 but not C or lapatinib. Pts with brain mets,including untreated or progressive mets, may be enrolled. 180 pts will be enrolled in North America and Europe. Pts are receiving C (1000 mg/mg2 PO BID for 14 days of a 21-day cycle) and T (8 mg/kg IV loading dose; 6 mg/kg IV once every 21 days), and are being randomized in a 2:1 ratio to ONT-380 300 mg PO BID or placebo. Pts with isolated CNS progression may continue on study treatment after undergoing local CNS therapy. An independent Data Monitoring Committee is monitoring pt safety.
Citation Format: Hamilton E, Borges V, Murthy R, Anders C, Cameron D, Carey L, Müller V, Curigliano G, Gelmon K, Hortobagy G, Krop I, Loibl S, Pivort X, Pegram M, Slamon D, Hurvitz S, Tsai M, Winer E. A phase 2 randomized, double-blinded, controlled study of ONT-380 vs. placebo in combination with capecitabine (C) and trastuzumab (T) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (MBC) (HER2CLIMB) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-02-09.
Abstract OT1-02-10: A phase 2 study of poziotinib in patients with HER2-positive metastatic breast cancer (MBC) who have received prior HER2 regimens for MBC
Authors: Lathrop K , Lucas J , Vacirca JL , Bhat G , Choi MR , Naughton M 
Published: March 2017

Abstract
Background: Poziotinib is a novel, oral, quinazoline-based pan-HER inhibitor that irreversibly blocks signaling through the epidermal growth factor receptor (EGFR) family of tyrosine-kinase receptors, including EGFR (HER1/ErbB1/EGFR), HER2 (ErbB2), and HER4 (ErbB4), as well as HER receptor mutations. This, in turn, leads to inhibition of the proliferation of tumor cells that overexpress these receptors. It is well established that breast cancers are associated with a mutation in, or overexpression of, members of the EGFR receptor family. The primary objective of this Phase 2 study is to evaluate the Objective Response Rate (ORR) of poziotinib in patients with human epidermal growth factor receptor 2 (HER2)-positive MBC. The secondary efficacy variables are Progression-Free Survival (PFS), Disease Control Rate (DCR), Overall Survival (OS), and Time to Progression (TTP).
Trial Design: This is a Phase 2, open-label, multicenter study to evaluate the efficacy, safety and tolerability of poziotinib in patients with HER2-positive MBC who have received at least 2 prior HER2- directed treatment regimens. Each treatment cycle is 21 days in duration. During each cycle, eligible patients receive 24 mg of poziotinib orally (as three 8-mg tablets) once daily for 14 days, followed by a 7 day treatment-free period.
Eligibility Criteria: Eligible patients are at least 18 years of age, have confirmed HER2 overexpression, adequate hematologic, renal and hepatic function, and have received at least 2 prior HER2-directed therapy regimens, including trastuzumab and trastuzumab emtansine (TDM-1). Patients are excluded if they have prior exposure to poziotinib, a history of congestive heart failure, left ventricular ejection fraction &lt;50%, unable to take oral medications, or have conditions that cause malabsorption. A 30 day wash out period from previous chemotherapeutic or radiation therapies is required.
Statistical Methods: The purpose of this study is to evaluate the efficacy of poziotinib compared to the efficacy of other standard HER2-positive breast cancer treatments as reported in the literature. The ORR will be analyzed descriptively along with the 95% CI. The secondary efficacy variables will be analyzed descriptively.
Target Accrual: Approximately 70 patients. Enrollment began February 2016.
Contact Information: For more information or to refer a patient,
email: spi-poz-201@sppirx.com or fax: 1-949-398-9711.
Citation Format: Lathrop K, Lucas J, Vacirca JL, Bhat G, Choi MR, Naughton M. A phase 2 study of poziotinib in patients with HER2-positive metastatic breast cancer (MBC) who have received prior HER2 regimens for MBC [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-02-10.
Abstract OT2-01-18: RIBECCA - A phase IIIb, multi-center, open label study for women with estrogen receptor positive locally advanced or metastatic breast cancer treated with ribociclib (LEE011) in combination with letrozole
Authors: Fasching PA , Decker T , Fehm T , Janni W , Kuemmel S , Lueftner D , Schneeweiss A , Schuler M , Guderian G , Schmidt-Wetzel S , Reiners R , Schubert J , Brucker S 
Published: March 2017

Abstract
Introduction:
The double blind, placebo-controlled MONALEESA-2 trial met its primary endpoint of clinically meaningful improvement in PFS at the pre-planned interim analysis for the combinatorial treatment of the cyclin-dependent kinase (CDK) 4/6-Inhibitor ribociclib and letrozole vs. letrozole monotherapy for postmenopausal, estrogen receptor positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) women who were naïve to treatment for advanced disease.
Here we present the national, multi-center, open-label, single-arm phase IIIb trial RIBECCA assessing the efficacy and safety of the combination of ribociclib and letrozole in an additional population, accompanied by a set of exploratory objectives.
Methods:
Main inclusion criteria allow enrollment of women with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy, and histological or cytological confirmation of ER+, HER2- breast cancer, irrespective of their menopausal status.
The primary objective is to assess the Clinical Benefit Rate (CBR) after 6 months, the secondary objectives include progression free survival (PFS), overall survival (OS), safety and change in quality of life.
The exploratory objectives include the assessment of biomarkers (e.g. ctDNA, CTCs, miRNA) predictive for response and the occurrence of adverse events of special interest. The influence of CDK4/6-inhibition on the immune system will be another exploratory endpoint of this study.
Conclusion:
With a planned recruitment of 500 patients in about 100 trial sites the RIBECCA trial will contribute to a better understanding of the safety, efficacy and possibly mechanisms related to CDK4/6-inhibition through ribociclib.
Citation Format: Fasching PA, Decker T, Fehm T, Janni W, Kuemmel S, Lueftner D, Schneeweiss A, Schuler M, Guderian G, Schmidt-Wetzel S, Reiners R, Schubert J, Brucker S. RIBECCA - A phase IIIb, multi-center, open label study for women with estrogen receptor positive locally advanced or metastatic breast cancer treated with ribociclib (LEE011) in combination with letrozole [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-18.
Abstract OT3-04-04: 21-gene recurrence score® in patients with primary metastatic ER+ HER2- breast cancer
Authors: Barinoff J , Anastasiadou L , Brandi C , Junker-Stein A , Silbermann J , Langenfeld M , Fortmann C , Thill M 
Published: March 2017

Abstract
Background and Purpose
Results from the 21-gene Recurrence Score (RS) are prognostic and predictive for recurrence in early breast cancer independent of clinical-pathological parameters. Prognostic information and distribution of RS in primary metastatic breast cancer (PMBC) was reported in a previous study by King et al but remains ultimately unclear in ER+ HER2- patients. We hypothesize that there is a prognostic correlation between RS and TTP/OS in PMBCindependent of clinical-pathological parameters, and the objective of the study is to evaluate the test for that cohort.
Patients and Trial Design
Between 2004 and 2014, 150 patients with first diagnosis of ER+/HER2- PMBC were enrolled in a multicenter, prospectively collected database. Pretreatment breast tumor samples will be analyzed by using 21-gene RS. Minimum follow-up will be 24 months.
Methods and Statistical Analysis
Patient characteristics, time to first progression (TTP), overall survival (OS) and treatment modalities will be described. The association between RS risk groups and both TTP and OS will be assessed by Kaplan-Meier estimates and compared with the log-rank test. Multivariate Cox regression models will be utilized to adjust for covariates. Additionally, assessing correlation of RS results using RS cut offs of 18 and 30 and additionally of 11 and 25 as well as analysis of quantitative ER from Oncotype DX assay for patients treated first-line with endocrine therapy are planned.
First results are expected to be presented in 2017.
Contact information for people with a specific interest in the trial:
Dr. Jana Barinoff
barinoff.jana@googlemail.com.
Citation Format: Barinoff J, Anastasiadou L, Brandi C, Junker-Stein A, Silbermann J, Langenfeld M, Fortmann C, Thill M. 21-gene recurrence score® in patients with primary metastatic ER+ HER2- breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-04-04.
Abstract OT3-04-05: Measuring the impact of MammaPrint on treatment in breast cancer patients: A prospective registry (IMPACt)
Authors: Soliman H , Untch S , Blumencranz L 
Published: March 2017

Abstract
This abstract was not presented at the symposium.
Citation Format: Soliman H, Untch S, Blumencranz L. Measuring the impact of MammaPrint on treatment in breast cancer patients: A prospective registry (IMPACt) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-04-05.
Abstract P1-02-05: Prognostic role of PIK3CA mutational status in circulating tumor DNA (ctDNA) from HER2-positive metastatic breast cancer patients
Authors: Lim J , Lee K-H , Min A , Kim S-G , Kim J-E , Kim T-Y , Han S-W , Oh D-Y , Kim T-Y , Lim S-A 
Published: March 2017

Abstract
Phosphatidylinositol-4, 5-biphosphate 3-kinase, catalytic subunit alpha (PIK3CA) is one of the most commonly mutated genes in breast cancer. But the prognostic and predictive role of PIK3CA mutations remains a matter of debate. It has been suggested that PIK3CA mutations are related to resistance to trastuzumab-based therapies, but they were also related to relatively indolent disease with better progression-free survival. Recently, circulating tumor DNA has been proposed to be a sensitive biomarker for detecting the presence of specific genetic aberrations in various cancer types, providing prognostic and predictive information. In this study, we evaluated prognostic and predictive role of PIK3CA mutations in patients with HER2-positive metastatic breast cancer treated with 1st line trastuzumab and taxane combination chemotherapy.
Thirty-four patients with blood samples obtained before 1st line trastuzumab and taxane combination chemotherapy were included in the study. We analyzed two PIK3CA hotspot mutations (E545K, H1047R) in ctDNA by digital droplet PCR (RaindropTM). The samples were collected from April 2005 to December 2011, centrifuged and stored as plasma, and were analyzed in 2015, after 4-10 years of storage period.
Median age was 47 years (range: 31 to 75 years), and histologic type of cancer was ductal carcinoma in all cases. PIK3CA mutations were detected in 21 (61.8%) of 34 patients. Patients with mutated PIK3CA in ctDNA had longer progression-free survival (PIK3CA wild type vs mutant, 11.0 months vs 22.0 months; P = 0.013). In hormone receptor positive group, patients with mutated PIK3CA had longer progression-free survival (PIK3CA wild type vs mutant, 12 months vs 18 months, P=0.17). Patients with PIK3CA mutations had a lower objective response rate than patients with wild-type, but there was no statistical significance (CR+PR; PIK3CA wild type vs mutant, 84.6% vs 66.7%, P=0.43). There was no significant difference in response rate (P = 0.48) or PIK3CA mutational status (P = 0.44) according to hormonal receptor status (estrogen receptor and/or progesterone receptor).
In conclusion, PIK3CA mutations were frequently detected by digital PCR from ctDNA of patients with HER2-positive breast cancer and they were related to significantly better PFS. We plan to analyze the PIK3CA mutation status in matched tumor tissue.
Citation Format: Lim J, Lee K-H, Min A, Kim S-G, Kim J-E, Kim T-Y, Han S-W, Oh D-Y, Kim T-Y, Lim S-A. Prognostic role of PIK3CA mutational status in circulating tumor DNA (ctDNA) from HER2-positive metastatic breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-05.
Abstract P1-02-08: Provista-002: A prospective, multi-center study to determine the effectiveness of a biomarker assay to distinguish benign from invasive breast cancer in women with BI-RADS 3, 4 and 5 imaging reports
Authors: Wolf J , Lourenco A , Alpers J , Rohatgi N , Constantini C , Hollingsworth A , Grobmyer S , Pederson H , Haythem A , Polen W , Northfelt D , Morris M , Baker K , Ghosh K , Kass F , Arterbery E , Yang R , Tran Q , Letsios E , Mulpuri R , Reese DE 
Published: March 2017

Abstract
This abstract was not presented at the symposium.