bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract OT2-03-03: A randomized trial of 15 fraction vs 25 fraction pencil beam scanning proton radiotherapy after mastectomy in patients requiring regional nodal irradiation
Authors: Mutter RW , Park SS , Hieken TJ , Vargas CE , Mei-Yin PC , Kathryn RJ , Hector VR , Kimberly CS , Elizabeth YS , Daniel VW 
Published: March 2017

Abstract
Background: Post-mastectomy radiotherapy improves survival in women with node-positive breast cancer. Pencil beam scanning proton therapy is attractive due to potential to reduce the dose to the heart and lungs compared with traditional photon techniques while improving conformality and limiting skin dose compared with passively scanned proton therapy. The optimal dose and fractionation for pencil-beam scanning proton therapy remains unknown.
Trial Design: This is a multi-center open label phase II randomized controlled trial to determine the safety of 15 fraction vs 25 fraction pencil beam scanning proton radiotherapy after mastectomy in patients requiring regional nodal irradiation.
Eligibility Criteria: Patients ≥ 18 years with primary, non-inflammatory invasive breast cancer who have undergone mastectomy with or without immediate reconstruction and chest wall and regional nodal irradiation planned.
Aims: To determine whether the 24 month complication rate (defined as grade 3 or greater late adverse events, and unplanned surgical intervention in patients who undergo mastectomy with reconstruction) of 15 fraction chest wall and regional node pencil beam scanning proton radiotherapy is acceptable relative to 25 fraction chest wall and regional nodal pencil beam scanning proton radiotherapy and worthy of further investigation.
Statistical methods: The study is designed as a non-inferiority/superiority “hybrid” design using the approach of Freidlin et al. It is Using a one-sided type I error rate of 0.05 (corresponding equivalently to constructing a 1-sided 95% confidence limit), 72 evaluable patients will have 80% power to reject the null hypothesis that the 24-month complication rate in the experimental arm is higher than that of the control arm by more than 10% (i.e. rule out inferiority) under the alternative hypothesis that the complication rate in the experimental arm is 5% less than that of the control arm (i.e. superiority). However, the design will have only 41% power when the two treatment arms are equivalent (i.e. the complication rate is 10% for both arms).
Accrual: The study opened in June 2016. Five of a planned eighty-two patients have been accrued to date.
Citation Format: Mutter RW, Park SS, Hieken TJ, Vargas CE, Mei-Yin PC, Kathryn RJ, Hector VR, Kimberly CS, Elizabeth YS, Daniel VW. A randomized trial of 15 fraction vs 25 fraction pencil beam scanning proton radiotherapy after mastectomy in patients requiring regional nodal irradiation [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 OT2-03-03.
Abstract OT2-04-01: Study on the usefulness of the skin wound therapeutic agent 'Neo dermal activator' in breast cancer surgery
Authors: Kim JH , Lim SM , Kim SI , Park SH , Park HS , Kim JY 
Published: March 2017

Abstract
Background : Wound infection after breast cancer surgery is considered to be factors that increase the discomfort of the patient and increase of the extension and the use of antibiotics in the treatment time period, in particular breast cancer postoperative wound infection resulting slow the implementation of adjunctive therapy such as radiation therapy or chemotherapy after surgery can cause, it is important to effectively prevent, there has been a development of a variety of skin wound therapeutic agent to reduce them. The purpose of this study was to evaluate the effects of the wound dressing with existing wound dressing Neo dermal activator compared to the patients receiving preoperative chemotherapy.
Methods : A total of 54 breast cancer patients who recieved BCS & mastectomy devided two group(each 27 patients) through the random assignment between Jan, 2016 and June, 2016. Day one weeks after surgery to examine the wound infection rate (surgical site infection, SSI rate). After six months of outpatient surgery visits to check the wounds of patients, using the VAS records the scar of the wound satisfaction. For patients who underwent radiation therapy, check out the time it took to begin radiation therapy after surgery.
All tests were two-sided. All statistical analyses were performed using SPSS version 20.0 (SPSS Inc., Chicago, Illinois, USA).
Eligbility criteria is :
- one side breast cancer
- not inflammatory breast cancer
- recieved BCS and mastectomy only (without immediate reconstruction surgery)
- stage IV breast cancer.
Citation Format: Kim JH, Lim SM, Kim SI, Park SH, Park HS, Kim JY. Study on the usefulness of the skin wound therapeutic agent 'Neo dermal activator' in breast cancer surgery [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 OT2-04-01.
Abstract OT3-01-01: A phase II study of PD-L1 and CTLA-4 inhibition and immunopharmcogenomics in metastatic breast cancer
Authors: Santa-Maria CA , Jain S , Flaum L , Park J-H , Kato T , Gross L , Uthe R , Tellez C , Stein R , Rademaker A , Gradishar WJ , Nakamura Y , Giles FJ , Cristofanilli M 
Published: March 2017

Abstract
Background
A hallmark of cancer is its ability to evade the immune system, however, it can be harnessed to detect and destroy cancer cells through inhibition of immune checkpoints such as CTLA-4 and PD-L1. This strategy has complementary and non-redundant mechanisms resulting in immune activation and antitumor synergy; progression free survival benefit has already been demonstrated in melanoma. A critical barrier in developing immunotherapies, however, is the identification of predictive biomarkers of response to therapy. Immunopharmacogenomic biomarkers, such as mutational burden, neoantigen profiles, and T cell receptor sequencing will elucidate the molecular interface between cancer and immune system, and may predict those most likely to benefit.
Methods
A single arm Phase II study was designed to determine the efficacy of PD-L1 and CTLA-4 inhibition and effects on immunopharmacogenomic dynamics in patients with metastatic breast cancer. The primary endpoint of this proposal is to investigate the response rate of the PD-L1 inhibitor, durvalumab, and the CTLA-4 inhibitor, tremelimumab, in metastatic breast cancer; secondary endpoints will examine the T cell receptor repertoire clonality, tumor mutational burden and neoantigen profiles. A total of 30 patients will be enrolled and treated with durvalumab 1500mg IV and tremelimumab 75mg IV monthly for 4 doses, then durvalumab 750mg every 2 weeks for 18 doses to complete 1 year of therapy with the option to renew therapy for an additional year; biopsies and blood at baseline and 2 months will be collected to assess immunopharmacogenomic biomarkers. Patients are eligible if they have triple negative or ER-positive breast cancer and have progressed on at least one line of chemotherapy and standard endocrine therapy if applicable. This is the first study to investigate immunopharmacogenomic biomarkers of response to dual checkpoint blockade in patients with metastatic breast cancer.
Citation Format: Santa-Maria CA, Jain S, Flaum L, Park J-H, Kato T, Gross L, Uthe R, Tellez C, Stein R, Rademaker A, Gradishar WJ, Nakamura Y, Giles FJ, Cristofanilli M. A phase II study of PD-L1 and CTLA-4 inhibition and immunopharmcogenomics in 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 OT3-01-01.
Abstract P1-02-01: Circulating tumor DNA analysis to predict relapse and overall survival in early breast cancer – Longer follow-up of a proof-of-principle study
Authors: Turner NC , Garcia-Murillas I , Chopra N , Beaney M , Kilburn L , Cutts R , Osin P , Nerurkar A , Schiavon G , Hrebien S , Bliss J , Dowsett M , Smith I 
Published: March 2017

Abstract
Background
In a previous proof-of-principle study we demonstrated that detection of circulating tumour DNA (ctDNA) in the adjuvant setting, after completion of surgery and chemotherapy for early stage breast cancer, was associated with a high risk of early relapse. Here we present longer follow-up of the same series, to define the predictive power of ctDNA analysis for disease free survival, and assess the potential to predict overall survival.
Methods
We recruited a cohort of 55 women presenting with early stage, primary breast cancer, who were all scheduled to receive neo-adjuvant chemotherapy. The primary tumour was sequenced to identify somatic mutations, identifying at least one mutation in 43 patients. Mutations were tracked with digital PCR to identify ctDNA, in plasma samples taken either at a single post-surgical time point (2-6 weeks post-surgery) or with serial plasma samples taken every 6 months in the adjuvant setting.
Results
At a median 31.7 months follow-up, 42% (18/43) patients had relapsed. Detection of ctDNA at the single post-surgical time point was associated with poor disease free survival, HR=13.6 95%CI (4.5, 41.2) p&lt;0.001, and overall survival HR=84.7 95%CI (9.8, 730.4) p&lt;0.001. All patients with ctDNA detected in a single post-surgical time point relapsed and died in the follow-up period (7/7, 100% specificity), although the single post-surgery time point had modest 39% (7/18) sensitivity for relapse. Detection of ctDNA at any point in serial sampling was associated with poor disease free survival HR=25.7 95%CI (8.3, 79.8) p&lt;0.001 and overall survival HR=47.1 95%CI (6.1, 366.1) p&lt;0.001. All patients with ctDNA detected in a serial mutation tracking relapsed in the follow-up period (14/14, 100% specificity), with 78% (14/18) sensitivity for relapse. Sensitivity was limited by 3 cases of brain only relapse and one case of solitary ovarian relapse. Detection of ctDNA in serial sampling had a median lead-time of 8.1 months over clinical relapse.
Conclusion
Detection of ctDNA in the adjuvant setting has a high predictive power for future relapse and death from breast cancer. Therapeutic trials are required to determine whether mutation tracking identifies relapse sufficiently early to allow for further adjuvant therapy.
Citation Format: Turner NC, Garcia-Murillas I, Chopra N, Beaney M, Kilburn L, Cutts R, Osin P, Nerurkar A, Schiavon G, Hrebien S, Bliss J, Dowsett M, Smith I. Circulating tumor DNA analysis to predict relapse and overall survival in early breast cancer – Longer follow-up of a proof-of-principle study [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 P1-02-01.
Abstract P1-02-13: Differential expression of exosomal miRNAs between breast cancer patients with recurrence and no-recurrence
Authors: Sueta A , Yamamoto Y , Tomiguchi M , Takeshita T , Ibusuki M , Iwase H 
Published: March 2017

Abstract
Background
In recent years, there has been a concerted effort to identify biomarkers derived from body fluid in various cancers. Exosomal microRNA (miRNA) has been used as one of useful diagnostic or prognostic biomarkers. We aimed to investigate the prognostic role of the exosomal miRNAs in serum samples derived from patients with primary breast cancer. Additionally, we evaluated whether the exosomal miRNA in serum reflect the origin of primary tumor by means of comparing their expression levels between in serum and tumors.
Patients and Methods
Exosomes in serum sample (500uL) were extracted using ExoQuick (System Biosciences) and miRNAs were isolated using SeraMirTM Exosome RNA Amplification Kit (SBI). We compared the miRNA profile derived from exosome between the patients with breast cancer with recurrence (n=16) and without recurrence (n=16) by miRNA PCR array. Further, we examined the expression of miRNA derived from tumor tissues in the patients with breast cancer recurrence (n=35) and without recurrence (n=39) by qRT-PCR. All samples were collected before treatment and surgery.
Results
Of the 384 miRNAs, 11 miRNAs were significantly expressed; three miRNAs (miR-338-3p, miR-340-5p, and miR-124-3p) were significantly up-regulated and eight (miR-29b-3p, miR-20b-5p, miR-17-5p, miR-130a-3p, miR-18a-5p, miR-195-5p, miR-486-5p, and miR-93a-5p) were significantly down-regulated in the patients with recurrence compared to those without recurrence. Next, we evaluated expression of the above miRNAs in tumor tissues. The patients with recurrence have higher levels of miR-340 at their primary site as well as in the serum. On the contrary, miR-195-5p, miR-17-5p, miR-93-5p, and miR-130a-3p derived from tumor tissues that were down-regulated in the patients with recurrence in serum, were highly expressed in the patients with recurrence than those with no-recurrence. In logistic regression analysis, tumor size, miR-340-5p, miR-17-5p, miR-130a-3p, and miR-93-5p were significantly associated with breast cancer recurrence (each P &lt; 0.05).
Conclusions
Several exosomal miRNAs at diagnosis may be useful biomarker to predict the breast cancer recurrence. Moreover, we showed the different expression pattern of miRNAs between tumor tissues and serum. These findings may suggest selective mechanism of release of exosomal miRNA by cancer cells to regulate their progression. Further studies to confirm our results are needed.
Citation Format: Sueta A, Yamamoto Y, Tomiguchi M, Takeshita T, Ibusuki M, Iwase H. Differential expression of exosomal miRNAs between breast cancer patients with recurrence and no-recurrence [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 P1-02-13.
Abstract P1-04-02: Improving immunotherapy response by epigenetic modulation
Authors: Luo N , Estrada VM , Sanders ME , Balko JM 
Published: March 2017

Abstract
The presence of predicted neo-antigens in any given tumor is highly correlated with total somatic mutational burden of the same tumor genome. However, many potential neo-antigens are never transcribed, translated, or presented as antigens, partially because they lie in regions of the genome that are transcriptionally-repressed by cytosine methylation of promoter-CpG islands. Treatment with DNA methyltransferase inhibitors (DNMTi) can hypothetically lead to re-expression of many potential neo-antigens. Furthermore, the presence of neo-antigens have been linked to immunotherapy outcomes in patients. Our hypothesis is that tumors with reduced mutational burden can be maximized for neo-antigen presentation by activating transcription and translation of these sequences through DNMTi treatment. Our preliminary results showed that the DNMTi guadecitabine (SGI-110), a second-generation hypomethylating agent, treatment decreases methyl-cytosine in genomic DNA both in vitro and in vivo. In addition, SGI-110 treatment enhances MHC-II expression on murine mammary carcinoma MMTV-Neu cells upon IFN-γ stimulation in vitro and increases T-cell infiltration in vivo. Currently, we are performing whole-exome-sequencing and RNA-sequencing to track somatic mutations from DNA to RNA. We will further track somatic mutations from RNA→ MHC-presented peptide sequences using MHC immunoprecipitation followed by mass spectroscopy analysis. In addition, we will explore the role of guadecitabine therapeutic priming on response to αPD-L1 immunotherapy. These studies will provide a pre-clinical data to evaluate the potential for combined epigenetic and immune-therapy in a clinical trial for breast cancer.
Citation Format: Luo N, Estrada VM, Sanders ME, Balko JM. Improving immunotherapy response by epigenetic modulation [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 P1-04-02.
Abstract P1-05-02: Genomic, transcriptomic and immune features of breast cancer according to the patient's body mass index at diagnosis
Authors: Desmedt C , Fornili M ,   ICGC Breast Cancer Working Group, Detours V , van den Eynden G , Salgado R , Maetens M , Brown D , Nik-Zainal S , Sotiriou C , Biganzoli E 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P1-05-16: An integrated molecular analysis of invasive lobular carcinoma
Authors: Lal S , McCart Reed A , Nones K , Wockner L , Song S , Lakhani S , Simpson P 
Published: March 2017

Abstract
Background: Invasive lobular carcinoma (ILC) is the most commonly diagnosed special histological type of breast cancer, accounting for up to 15% of all cases. Accumulating data suggests the biology and clinical features of ILC differ to those of the more commonly diagnosed Invasive Carcinoma of No Special Type (IC-NST), including evidence of there being an overall worse long term outcome associated with ILC. Several large-scale molecular profiling studies have recently been published regarding ILC, highlighting molecular heterogeneity and important drivers of tumour behaviour. We hypothesize that an integrative analysis of gene expression and DNA copy number data will identify novel drivers, and prognostic and predictive biomarkers of lobular phenotype.
Methods: Gene expression and copy number data from ILC tumours profiled in-house (n=25), METABRIC (n=125) and TCGA (n=145) were assembled and analysed. Integration of genome and transcriptome data was performed using two methods. Firstly, by Spearman correlation with a meta-analysis by combining gene level correlation coefficients from each study using a random effects model, weighting each study with inverse variance. Secondly using ANOVA, followed by combining gene level p-values across studies using Stouffers Z-score. Disease specific survival was examined at an individual gene level and using all genes simultaneously (via a Cox Boost analysis) to identify gene expression changes that are associated with poor outcome.
Results: DNA copy number profiling identified recurrent gains (1q, 8q, 16p), losses (11q, 16q) and amplifications (1q32, 8p12-p11.2, 11q13). 11q13 amplifications were prevalent at a higher frequency in patients with poor outcome compared to patients with better outcome. The integrative analysis identified 1928 candidate genes whose expression was associated with gene copy number; as expected being enriched from genome regions highlighted above. One hundred and sixty of these genes were of prognostic significance in the METABRIC ILC cohort, several are known cancer drivers (e.g. PBX1, CCND1) and five new candidates are being investigated as novel prognostic biomarkers by immunohistochemistry.
Conclusions: An integrated molecular analysis of ILC has identified a large number of gene expression changes that are dictated by gene copy number in ILC. Some of these are expected to influence tumour behavior and to highlight aggressive cancers with poor prognosis.
Citation Format: Lal S, McCart Reed A, Nones K, Wockner L, Song S, Lakhani S, Simpson P. An integrated molecular analysis of invasive lobular carcinoma [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 P1-05-16.
Abstract P1-11-07: Frozen section histology evaluation of surgical margins helps perform single step oncologically safe and cost-effective breast conservation surgery
Authors: Agarwal G , Sonthineni C , Maylivahanan S , Chand G , Mishra A , Agarwal A , Verma AK , Mishra SK , Agrawal V , Krishnani N , Lal P 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P1-11-14: Breast conserving therapy and mastectomy revisited: overall and breast cancer-specific survival and the influence of age, stage, receptor status and comorbidities in 143,376 patients
Authors: Lagendijk M , van Maaren MC , Saadatmand S , Strobbe LJA , Poortmans P , Koppert LB , Tilanus-Linthorst MMA , Siesling S 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P2-01-29: In the era of conservative surgery, can patients presenting with node positive breast cancer be spared axillary node dissection post neoadjuvant chemotherapy? A meta-analysis and review of literature
Authors: Headon H , Chehade HEH , El Tokhy O , Wazir U , Heeney J , Kasem A , Mokbel K 
Published: March 2017

Abstract
Background:The use of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes remains controversial.
Methods: A computer-aided search of the literature regarding SLNB in clinically node-positive breast cancer treated with NAC was carried out to identify the false negative rate (FNR), sentinel lymph node identification rate (IR), and axillary pathological complete response (pCR).
Results: Nineteen articles were used in the analysis yielding 3398 patients. The pooled estimate of the FNR was 13% and that of the IR was 91%. The adjusted pCR rate was 47%.
Conclusions: SLNB after NAC in biopsy-proven node positive patients results in reasonably acceptable FNR and IR making it a valid alternative management strategy to axillary dissection. Although the results are not matched with those in clinically node negative patients, a FNR of 13% is very unlikely to adversely affect overall survival. Its impact on locoregional recurrence should be evaluated in adequately powered future studies. More refined patient selection and optimal techniques can improve the FNR and IR in this patient population.
Citation Format: Headon H, Chehade HEH, El Tokhy O, Wazir U, Heeney J, Kasem A, Mokbel K. In the era of conservative surgery, can patients presenting with node positive breast cancer be spared axillary node dissection post neoadjuvant chemotherapy? A meta-analysis and review of literature [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 P2-01-29.