bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES8-1: Spatial and temporal evolution of breast cancer
Authors: Yates Lucy 
Published: May 2015

Abstract
Cancers are ecosystems of genetically related clones, competing across space and time for limited resources. To understand the clonal structure of breast cancers we applied a combination of high depth targeted capture and whole genome sequencing to multiple samples from individual primary breast cancers and metastases. Our work has identified that the extent of subclonal diversification within the primary tumor varies considerably among patients and encompasses many spatial patterns, including local growth, intraductal dissemination and clonal intermixture. Landmarks of disease progression, such as acquiring invasive or metastatic potential are frequently associated with the emergence of distinct driver events and sometimes arise within detectable subclones of antecedent lesions, suggesting that subclonal mutations in the primary tumor could be relevant if actionable. The impact of structural variation on the breast cancer driver landscape is relatively understudied, but our work indicates that structural variation frequently makes a major contribution to the somatic mutational landscape late in disease evolution. Thus, the interplay of mutation, growth and competition drives clonal structures of breast cancer that are complex, variable across patients and clinically relevant.
Citation Format: Lucy Yates. Spatial and temporal evolution of breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES8-1.
Abstract ES8-3: Epigenetic heterogeneity in cancer
Authors: Polyak Kornelia 
Published: May 2015

Abstract
Heterogeneity of cancer cells within tumors is a major challenge in clinical oncology as it underlies tumor progression and therapeutic resistance. Cancer cells can have varying genotypes, epigenetic states such as DNA methylation and chromatin patterns, and phenotypes. The high frequency of somatic mutations in genes encoding for epigenetic regulators and transcription factors in breast cancer highlight the importance of perturbed epigenetic programs in breast tumorigenesis. Some forms of epigenetic heterogeneity within tumors is due to variability for cellular differentiation states such as luminal and basal features, whereas other forms reflect transient cellular states sometimes triggered by microenvironmental signals. Cellular epigenetic heterogeneity within tumors thought to play key roles in metastatic progression and therapeutic resistance. Thus, its better understanding and our ability to modulate it are critical for the design of more effective cancer treatment strategies. In contrast to genetic alterations, epigenetic states are reversible and due to intense research in this area, the number of compounds for their modulation is rapidly increasing. Because epigenetic modulators likely to work best in combination with other agents, the design of clinical trials testing their efficacy requires novel approaches.
Citation Format: Kornelia Polyak. Epigenetic heterogeneity in cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES8-3.
Abstract ES9-3: Adjuvant and neoadjuvant therapy: Current practice and future approaches
Authors: Winer Eric P. 
Published: May 2015

Abstract
Triple negative breast cancer (TNBC) is accounts for approximately 10-15% of all breast cancer and is associated with a higher risk of disease recurrence, particularly early recurrence, than the other breast cancer subtypes. From a genomic standpoint, TNBC is heterogeneous, though we do not know how to incorporate this heterogeneity in treatment decisions. At the present time, there are no targeted systemic therapies for TNBC, and standard/neoadjuvant treatment consists of chemotherapy. Most treatment regimens include both an anthracyline and a taxane and involve 6-8 cycles of therapy, though simpler regimens such as AC x 4, TC x 4, or CMF x 6 remain an option for patients with a stage I disease. Neoadjuvant chemotherapy is often administered to decrease the extent of breast or axillary surgery. Outside of a clinical trial, anthracycline/taxane-based regimens remain the standard of care in the neoadjuvant setting. The addition of the platinum salts to standard therapy increases the proportion of patients who achieve a pathologic complete response, but it is unclear if these agents extend disease-free or overall survival. It is also unknown which patients benefit from the platinum salts and whether these agents should be added to or substituted for some portion of the standard regimen. Other investigational regimens, such as those including the PARP inhibitors, are also being studied in the neoadjuvant setting. On an individual patient level, response to neoadjuvant therapy is closely tied to outcome. Patients with a pathologic complete response have a far better outcome than those with residual disease, particularly those with extensive residual disease. However, it is unknown if the achievement of a higher pathologic complete response within a comparative trial leads to an improvement in disease-free or overall survival. Similarly, it is unknown if the addition of agents such as the platinum salts or other investigational treatmens can reduce the risk of recurrence in patients with residual disease after standard therapy. Ultimately, improved outcomes will be achieved through carefully controlled adjuvant and neoadjuvant trials conducted in close collaboration with laboratory investigators. It is likely that our understanding of the underlying biology of triple negative disease as well as our treatment approaches will evolve significantly in the next decade.
Citation Format: Eric P. Winer. Adjuvant and neoadjuvant therapy: Current practice and future approaches [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES9-3.
Abstract MS1-1: Characterising cancer risks for carriers of mutations in BRCA1, BRCA2, PALB2, and RAD51C genes
Authors: Antoniou Antonis C. 
Published: May 2015

Abstract
The presentation will provide an overview of the latest developments and challenges in understanding the penetrance of mutations in the BRCA1, BRCA2, PALB2 and RAD51C genes. Genetic counselling currently relies on average cancer risk estimates obtained from retrospective penetrance studies involving large numbers of families segregating mutations in these genes. The talk will present penetrance estimates from ongoing prospective analyses, based on data from the International BRCA1/2 Carrier Cohort Study, the largest cohort of BRCA1/2 mutation carriers worldwide that includes &gt;10,000 mutation carriers at baseline with prospective follow-up information. Several common alleles and other risk factors have now been shown to modify breast cancer risk for BRCA1 and BRCA2 mutation carriers. The talk will review the latest efforts and results from the Consortium of Investigators of Modifiers of BRCA1/2 to identify genetic modifiers of risk and provide individualised cancer risks for BRCA1 and BRCA2 mutation carriers on the basis of polygenic risk scores. We will also present penetrance estimates based on analyses of combined data from families segregating mutations in PALB2 and RAD51C, the largest efforts of their kind. Finally the presentation will demonstrate how the effects of common and rare breast cancer susceptibility variants are incorporated into the BOADICEA model to provide comprehensive risks of developing breast cancer in the future.
Citation Format: Antonis C. Antoniou. Characterising cancer risks for carriers of mutations in BRCA1, BRCA2, PALB2, and RAD51C genes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr MS1-1.
Abstract OT1-1-06: A phase I study of LDE225 in combination with docetaxel in patients with triple negative (TN) advanced breast cancer (ABC): GEICAM/2012-12 (EDALINE study)
Authors: Martin Miguel , Ruiz-Borrego Manuel , Trigo José M , Antolin Silvia , Garcia-Saenz Jose A , Hernando Andres , Ocaña Alberto , Rojo Federico , Lopez-Tarruella Sara , Corral Jesus , Ribelles Nuria , Calvo Lourdes , Moreno Fernando , Caballero Rosalia , Carrasco Eva 
Published: May 2015

Abstract
Background: LDE225 is a potent and selective oral inhibitor of Smo, a key component of the hedgehog (Hh) signaling pathway. Up-regulation of the Hh pathway is implicated in the genesis of a wide range of tumors including triple negative breast cancer. Here we report an ongoing phase I study exploring the combination of LDE225 with docetaxel in TN ABC patients to identify the Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) (ClinicalTrials.gov Identifier: NCT02027376).
Trial Design: Eligibility criteria include patients with TN ABC candidates to receive treatment with docetaxel that have received a maximum of 3 prior chemotherapy regimens. Those patients with CNS involvement are also candidates if treated and clinically stable. Treatment consists of 21-day cycles with docetaxel 75mg/m2 on day 1, every 21 day and LDE225 once daily. We use a standard 3+3 design in sequential cohorts (3 dose levels (DL) of LDE225: 400mg once daily (DL1), 600mg once daily (DL2), 800mg once daily (DL3); and a DL-1: LDE225 400mg once daily and docetaxel 60mg/m2 every three weeks). The primary endpoint is the MTD and RP2D of the combination; secondary endpoints include evaluation of safety and tolerability, in addition to pharmacodynamic (PD) and pharmacokinetic (PK) studies. Patients are treated until radiologic or symptomatic progression or unacceptable toxicity occurs. PK will be performed to evaluate whether LDE225 influences the pharmacology of docetaxel. PD assessments include Hg gene expression signature associated to pathway activation in tumor samples and changes in Smo related biomarkers in skin and blood correlative samples. Efficacy will be measured in terms of time to progression and objective response rate. A minimum of 9 and a maximum of 18 patients will be included in this phase I. The study is approved by ERBs and Competent Authority and already recruiting patients (two patients included in DL1).
Citation Format: Miguel Martin, Manuel Ruiz-Borrego, José M Trigo, Silvia Antolin, Jose A Garcia-Saenz, Andres Hernando, Alberto Ocaña, Federico Rojo, Sara Lopez-Tarruella, Jesus Corral, Nuria Ribelles, Lourdes Calvo, Fernando Moreno, Rosalia Caballero, Eva Carrasco. A phase I study of LDE225 in combination with docetaxel in patients with triple negative (TN) advanced breast cancer (ABC): GEICAM/2012-12 (EDALINE study) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-1-06.
Abstract OT2-4-02: Testing BRCA 1/2 mutation using next generation sequencing (BRCANGS)
Authors: Park Hyung Seok , Park Seo Jin , Kim Sanghwa , Ryu Jegyu , Kim Jee Ye , Park Seho , Kim Seung Il , Sohn Joo Hyuk , Choi Jong Rak 
Published: May 2015

Abstract
Testing BRCA 1/2 mutation is important for patients with breast cancer, and Sanger sequencing is a standard method to identify BRCA 1/2 mutation. Next generation sequencing (NGS) is a high-throughput parallel sequencing that can provide genetic information with high accuracy. NGS is a faster and cost-effective method to detect gene mutations compared to Sanger sequencing. This study is a prospective non-randomized obsevational study which evaluates the clinical role of NGS testing for BRCA 1/2 compared to Sanger sequencing. Eligibility criteria are wome aged 19 to 80 years, patients with breast or ovarian cancer history in 2nd degree family members, male breast cancer, bilateral breast cancer, patient with breast cancer under 40 year of age, simultaneous breast and ovarian cancer, patients with epithelial ovarian cancer, and breast cancer with other simultaneous extramammary malignancy. Primary endopont of the study is the overall accuracy of NGS compared to Sanger sequencing. Seconary endponts are sensitivity, specifcity, false negative, and false positive rates of NGS compared to Sanger method. Target accrual of the pilot study is 12 patients, and futher extension of patients accrual is scheduled after the anlaysis of the pilot study. This study is approved by institutial review board of Severance Hospital. The study is conducted and planned by Prof. HS Park, Yonsei University College of Medicine, Seoul, Korea and supported by Korea Breast Cancer Foundation. ClinicalTrials.gov identifier is NCT02151747.
Citation Format: Hyung Seok Park, Seo Jin Park, Sanghwa Kim, Jegyu Ryu, Jee Ye Kim, Seho Park, Seung Il Kim, Joo Hyuk Sohn, Jong Rak Choi. Testing BRCA 1/2 mutation using next generation sequencing (BRCANGS) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT2-4-02.
Abstract OT2-5-01: Brain metastases in breast cancer network Germany (BMBC, GBG 79): Multicentric, retro- and prospective collection of patient data and biomaterial from breast cancer patients with brain metastases
Authors: Witzel Isabell , Laakmann Elena , Fehm Tanja , Möbus Volker , vonMinckwitz Gunter , Kaiser Julia , Loibl Sibylle , Müller Volkmar 
Published: May 2015

Abstract
Background: The incidence of brain metastases in breast cancer patients is rising and has become a major clinical challenge in the last years. So far, limited therapeutic options and insights into the biology of brain metastases exist. Most reports include patients with brain metastases from different tumor entities and few studies so far analyzed exclusively patient data or tumor samples from breast cancer patients. In this context, an open, multicenter registry and biobank should be helpful for analysis of a large number of breast cancer patients with brain metastases. Therefore, we initiated the Brain Metastases in Breast Cancer Network Germany (BMBC; GBG79).
Trial design and eligibility criteria: Patients with brain metastases from breast cancer are eligible. Registration of patient data is allowed retrospectively and prospectively. To enable an easy access, an internet-based database was chosen ("MedCodes" by the German Breast Group).
Specific aims: Documented data cover incidence, symptoms, number and localization of brain metastases, histopathology, imaging methods, outcome, therapy, and quality of life measurement. Tissue of brain metastases and primary tumors will be collected for translational research projects. Planned analyses include treatment patterns in Germany, patient outcome, as well as validation of prognostic scoring systems in a multicenter setting and in the context of new targeted therapies. Translational research projects investigate the impact of glycosylation, resistance mechanisms against HER2-targeted therapies, role of the blood brain barrier, evaluation of markers of radioresistance and specific genomic alterations associated with brain tropism of breast cancer cells. The registry and biobank should be also open for cooperation with other groups.
Present accrual and target accrual: The accrual target is app. 1000 patients in the database and app. 400 tissues of brain metastases from German centers. The study was opened for documentation in April 2014 with more than 50 participating centers as of June 2014.
Citation Format: Isabell Witzel, Elena Laakmann, Tanja Fehm, Volker Möbus, Gunter vonMinckwitz, Julia Kaiser, Sibylle Loibl, Volkmar Müller. Brain metastases in breast cancer network Germany (BMBC, GBG 79): Multicentric, retro- and prospective collection of patient data and biomaterial from breast cancer patients with brain metastases [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT2-5-01.
Abstract P1-01-10: A preoperative PET/MR imaging for diagnosing malignant axillary lymph nodes in women evaluated for breast cancer
Authors: Yeu Kyung Jun , Park Jeong Yeong , Choi Jung Eun , Kang Su Hwan , Kong Eun-Jung , Cho Ihn-Ho , Lee Soo Jung 
Published: May 2015

Abstract
Objective: We determined whether and how malignant node could be diagnosed preoperatively with simultaneous PET/MR imaging.
Materials and methods:Two hundred thirty-six consecutive women with breast cancer were recruited to undergo preoperative PET/MR imaging. 52 patients were excluded; 31 DCIS, 7 neoadjuvant chemotherapy and 14 previous excisional biopsy. Thus, 184 women (51.9 ±10.2 years old) were included. Axial T1w without fat saturation, contrast enhanced image and diffusion-weighted images with simultaneous acquired PET images were analyzed by nuclear medicine physicians who were blinded the histologic findings. Visual FDG avidity, long axis and cortical thickness of axillary lymph node (ALN), morphologic feature-loss of fat hilum, cortical thickening, round shape or irregular shape- and ADC value were analyzed in most suspicious ALNs.
Results:In total, 70 patients (15 patients have only micrometastasis) exhibited ALN metastasis. Mean size of breast mass was 2.1 ±1.5 cm. Macrometastatic ALN showed high FDG uptake, longer axis, thicker cortex, more frequent morphologic abnormalities, higher signal intensity at DWI and higher ADC values with statistical significance. No significant difference between micrometastatic ALN and benign ALN in PET/MR imaging. With pathologic diagnosis as the reference standard, the sensitivity, specificity and accuracy of PET for determining ALN metastasis were 84%, 58% and 68%, respectively. Those are 77%, 84% and 82% in considering both PET with morphologic change and 81%, 66% and 72% in considering PET, morphologic change and DWI, respectively.
Conclusion:PET/MR imaging techniques showed high accuracy in the preoperative evaluation of axillary status in patients with breast cancer. Additional information by DWI is unlikely to be useful in predicting metastatic ALN.
Citation Format: Kyung Jun Yeu, Jeong Yeong Park, Jung Eun Choi, Su Hwan Kang, Eun-Jung Kong, Ihn-Ho Cho, Soo Jung Lee. A preoperative PET/MR imaging for diagnosing malignant axillary lymph nodes in women evaluated for breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-01-10.
Abstract P1-01-12: Preoperative breast MRI does not affect survival outcomes in T1-2 breast cancer patients who underwent breast-conserving therapy
Authors: Ryu Jegyu , Kim Sanghwa , Kim Jee Ye , Park Hyung Seok , Park Seho , Kim Seung il 
Published: May 2015

Abstract
Purpose: The aim of the study is to evaluate the efficacy of preoperative breast MRI in T1-2 women with breast cancer.
Methods: Total 1179 patients, who had T1-2 breast cancer and underwent definitive surgery between 2007 and 2010, were reviewed in this study. Preoperative breast MRI was performed in 981 women with breast cancer. We divided patients into two groups: Patients underwent preoperative MRI and breast-conserving therapy (BCT), those who did not undergo preoperative MRI but BCT. Patients underwent preoperative MRI and total mastectomy were excluded. Clinicopathological features were analyzed using Chi-square or Fisher’s exact test if indicated. Survival analyses were examined using Kaplan-Meier method and log-rank test. Cox-proportional hazard model was accessed as multivariate analysis.
Results: In 873 patients who underwent BCT, 675 patients (77.3%) received preoperative MRI, and 198 (22.7%) patients did not. Clinicopathological features including T-stage, Nodal status, histologic type, progesterone receptor, histologic grade, age group (≤ 35 vs. &gt; 35 yr), adjuvant chemotherapy, radiation, and hormone therapy were not significantly different between two groups. Patients aged 50 or younger received more preoperative MRI than those over aged 50 years (42.8 % vs. 51.5%, p=0.02). Estrogen receptor positive-tumors were more common in patients with preoperative MRI (74.9% vs. 67.2%, p=0.03). HER2 over-expression was frequently found in women without preoperative MRI (7.9% vs. 14.6%, p&lt;0.001). In univariate analyses, there was no significant difference in recurrence-free and overall survival between patients who underwent breast MRI and those who did not (p for RFS = 0.75, p for OS = 0.48). In multivariate analyses, preoperative MRI did not influence on RFS and OS (HR for RFS = 0.82, 95%CI= 0.35-1.91, HR for OS = 1.52, 95% CI= 0.40-5.76). Age group and HER2 were not associated with RFS and OS (all p&gt;0.05). ER was an independent prognostic factor for RFS and OS (all p&lt;0.01).
Conclusions: Routine use of preoperative MRI in women with T1-2 breast cancer may not translate into better RFS and OS.
Citation Format: Jegyu Ryu, Sanghwa Kim, Jee Ye Kim, Hyung Seok Park, Seho Park, Seung il Kim. Preoperative breast MRI does not affect survival outcomes in T1-2 breast cancer patients who underwent breast-conserving therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-01-12.