bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-10-09: The impact of Charlson comorbidity index on survival of triple negative breast cancer
Authors: Parise C , Caggiano V 
Published: May 2019

Abstract
Background
Patients with cancer and comorbidities have been found to have poorer survival since they may be unable to receive or complete treatments. It is not clear if comorbid conditions impact survival of patients in all stages of disease and all ER/PR/HER2 subtypes.
Purpose
The purpose of this study was to determine how the Charlson Comorbidity Index (CCI) affected the risk of mortality of triple negative breast cancer (TNBC) within each stage of disease.
Methods
We accessed 22,503 cases of TNBC and documented CCI from the California Cancer Registry 2000-2015. The CCI is a weighted index based on the presence of certain comorbid conditions twelve months prior through six months following the cancer diagnosis and weighted by the severity of those conditions. A score of 0 is interpreted as no significant comorbidity burden and scores of 3 or more are generally interpreted as a high comorbidity burden.
Kaplan-Meier Survival Analysis and the Log Rank test were used to compare differences in breast cancer specific survival between patients with a CCI of 1, 2 or higher (2+) versus a CCI of 0. Cox Regression Analysis was used to estimate risk of mortality of CCI after adjusting for age, race/ethnicity, socioeconomic status, grade, and treatment. Analyses were conducted separately for each stage. Hazard ratios and 95% confidence intervals (CIs) were reported.
Results
There 16,664 (74.1%) cases with a CCI of 0; 3,915 (17.4%) with a CCI of 1; 1,055 (4.7%) had a CCI of 2, and the remaining 869 (3.9%) cases of TNBC had a CCI of 3 or higher.
Unadjusted survival analysis indicated that for stages 2 and 3, there was increased survival with decreasing CCI score. For stages 1 and 4, survival was only better for patients with a CCI of 0 versus a CCI of 2+.
Cox regression analysis indicated that the CCI made no difference in risk of mortality for patients with stage 1 disease. Patients with a CCI of 2+ had an increased risk of mortality when compared with a CCI of 0 for stage 2 (HR = 1.48, CI: 1.25-1.77), stage 3 (HR=1.25, CI: 1.03-1.52) and stage 4 (HR = 1.53; CI: 1.22-1.92).
Conclusion
Comorbidity as measured by the CCI does not increase the risk of mortality for patients with stage 1 TNBC and only increases risk of mortality in higher stages for patients with a CCI score of 2 or higher.
Citation Format: Parise C, Caggiano V. The impact of Charlson comorbidity index on survival of 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 P4-10-09.
Abstract P4-10-17: Plasma metabolomic signatures associated with long-term breast cancer risk in the SU.VI.MAX prospective cohort
Authors: Lucie L , Céline D , Bernard L , Aicha D , Adrien R , Marie-Paule V , Mélanie P , Marie L , Tom F , Delphine C , Laurent Z , Pilar G , Serge H , Mélanie D , Valentin P , Bernard S , Paule L-M , Emmanuelle K-G , Nathalie D-P , Claudine M , Stéphanie D , Estelle P-G , Mathilde T 
Published: May 2019

Abstract
Purpose: Breast cancer is a major cause of death in occidental women. Mechanisms involved in its etiology remain misunderstood. Metabolomics is a powerful tool which may help elucidating novel biological pathways and identify new biomarkers in order to predict breast cancer well before symptoms appear. The aim of this study was to investigate whether untargeted metabolomic signatures from blood draws of healthy women could contribute to better understand and predict the long-term risk of developing breast cancer.
Methods: A nested case-control study was conducted within the SU.VI.MAX prospective cohort (13 years of follow-up) to analyze baseline plasma samples of 211 incident breast cancer cases and 211 matched controls by LC-MS mass spectrometry. Multivariable conditional logistic regression models were computed.
Results: 83 ions were significantly associated (corrected-pvalue &lt;0.05) with breast cancer risk. Notably, we observed that a lower plasma level of O-succinyl-homoserine and higher plasma levels of valine/norvaline, glutamine/isoglutamine, 5-aminovaleric acid, phenylalanine, tryptophane, γ-glutamyl-threonine, ATBC, 2-amino-cyanobutanoic acid and pregnene-triol sulfate were associated with an increased risk of developing breast cancer during follow-up. Corrected-pvalues ranged from 0.009 (OR=1.43[1.14-1.78] for phenylalanine and OR=1.45[1.15-1.83] for valine/norvaline) to 0.03 (OR=1.28[1.03-1.58] for 2-amino-cyano-butanoic acid).
Conclusion: Several pre-diagnostic plasmatic metabolites are strongly associated with long-term breast cancer risk. If confirmed in other independent cohort studies, these results could help to identify healthy women at higher risk of developing breast cancer in the subsequent decade and to propose a better understanding of the complex mechanisms involved in its etiology.
Trial registration: SU.VI.MAX, clinicaltrials.gov NCT00272428. Registered 3 January 2006
Keywords: Metabolomics, breast cancer, mass spectrometry, plasma, prospective study
Citation Format: Lucie L, Céline D, Bernard L, Aicha D, Adrien R, Marie-Paule V, Mélanie P, Marie L, Tom F, Delphine C, Laurent Z, Pilar G, Serge H, Mélanie D, Valentin P, Bernard S, Paule L-M, Emmanuelle K-G, Nathalie D-P, Claudine M, Stéphanie D, Estelle P-G, Mathilde T. Plasma metabolomic signatures associated with long-term breast cancer risk in the SU.VI.MAX prospective cohort [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 P4-10-17.
Abstract P4-14-10: Withdrawn
Authors: Ekholm M , Bendahl P-O , Fernö M , Nordenskjöld B , Stål O , Rydén L 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Ekholm M, Bendahl P-O, Fernö M, Nordenskjöld B, Stål O, Rydén L. Withdrawn [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 P4-14-10.
Abstract P5-02-06: High-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy: Imaging characteristics, outcome of surgical excision or imaging follow-up
Authors: Okamoto S , Covelli JD , DeMartini WB , Daniel BL , Ikeda DM 
Published: May 2019

Abstract
PURPOSE
To evaluate imaging characteristics, outcome of surgical excision or imaging follow-up on high-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy (MRI-VAB).

MATERIALS AND METHODS
We retrospectively reviewed 581 lesions, to include benign, high-risk and malignant lesions, undergoing 9-gauge MRI-VAB from January 2015 to April 2018. We collected patient demographics, risk factors and indications, breast MRI BI-RADS descriptors, histopathological diagnosis at MRI-VAB and surgical excision, frequency of upgrade to malignancy and imaging follow-up of high-risk lesions found in this period.
RESULTS
101 patients with 107/581 (18.4% of all lesions) had high risk lesions at MRI-VAB, including atypical ductal hyperplasia (ADH)(n=19/107, 17.8%), lobular neoplasia (n=35/107, 32.7) including atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), ALH plus LCIS, papillary lesions (n=44/107, 41.1%), radial scar/complex sclerosing lesion (RS/CSL)(n=8/107, 7.5%) and flat epithelial atypia (FEA)(n=1/107, 1%). 71/107 (66.4%) high risk lesions were excised. 16/71 (22.5%) were upgraded to malignancy (4 invasive cancer, 12 DCIS). The upgrade rate for ADH and lobular neoplasia was 5 /16 (31.3%) and 8/26 (30.8%) respectively. The upgrade rate for RS/CSL was 1/6 (16.7%). Of the 22 papillary lesions excised, 2 (9.1%) demonstrated pathologic atypia and were upgraded to DCIS. The other 20 papillary lesions had no upgrade or atypia. Excised high risk lesions showing upgrade varied from 0.4 to 6 cm in length (average 2.1 cm). Increasing size correlated with tendency towards increased upgrade to malignancy, but there were no other specific imaging features to predict malignancy upgrade.
CONCLUSION
There were no specific MRI imaging characteristics of high-risk lesions to predict malignancy upgrade. Therefore, surgical excision is recommended for high risk lesions especially ADH or lobular neoplasia. Additionally, non-atypical papillomas did not demonstrate malignancy upgrade in our small study. And further larger studies may demonstrate that these lesions may not need to be surgically excised.
Citation Format: Okamoto S, Covelli JD, DeMartini WB, Daniel BL, Ikeda DM. High-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy: Imaging characteristics, outcome of surgical excision or imaging follow-up [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 P5-02-06.
Abstract P5-03-09: LINC00624 binding with SFPQ/MATR3/ NONO protein complexes enhances resistance to neoadjuvant therapy in HER-2 positive breast cancer by inhibiting tumor immune response
Authors: Zhang Q , Xiu B , Chi Y , Chi W-R , Wu J 
Published: May 2019

Abstract
Background
Neoadjuvant chemotherapy(NAC) has been widely used for its ability to downstage breast cancer. With anti-HER2 therapy, around half of the HER2 positive patients achieve pCR after NAC. However, treatment failure is still a concern and leads to a worse prognosis. New biomarkers and biological mechanisms are waiting to be discovered to tackle this problem.
Methods
RNA-Seq was performed to identify differently expressed RNAs between pCR and non-pCR group. The IC50 value was measured by CCK-8 assay in HER-2 positive cells (SK-BR-3 and JIMT-1). Quantitative RT-PCR (qRT-PCR) was used to detect the expression levels of LINC00624 and its potential target genes. RNA-seq and GSEA analysis was carried out to determine the target pathways regulated by LINC00624.
Results
Core needle biopsy tissue from HER-2 positive patients was collected before NAC. LINC00624 was found to be down regulated in pCR group compared with non-pCR group by RNA-seq. High expression of LINC00624 was associated with poor overall survival in TCGA database and our own patients cohort. Overexpression of LINC00624 promoted cell proliferation and colony-forming ability. Meanwhile, the IC50 values of Paclitaxel and Trastuzumab in HER-2 positive breast cells were decreased by LINC00624. Via RNA pull-down assay and mass spectrometry, the SFPQ/MATR3/NONO protein complex, which was reported to be associated with the innate immune system, was found to interact with LINC00624. RNA-seq further revealed that several immunological and inflammatory factors, including 'IFN-α response', 'IFN-γ response' and 'TNF-α via NF-κB' were suppressed by LINC00624. IFN downstream molecules were inactivated in LINC00624 overexpressing cells following TNF-α, IFN-α, IFN-β and poly (I:C) treatment, which implies the immune inhibition ability of LINC00624 .
Conclusion
LINC00624 is associated with resistance to NAC in HER-2 positive breast cancer. It binds with the SFPQ/MATR3/NONO complex and desensitizes cell response to chemotherapy and anti-HER2 agents via suppressing immunological and inflammatory effect. This study suggests that LINC00624 could serve as a biomarker to predict therapy response to NAC in HER-2 positive breast cancer.
Citation Format: Zhang Q, Xiu B, Chi Y, Chi W-R, Wu J. LINC00624 binding with SFPQ/MATR3/ NONO protein complexes enhances resistance to neoadjuvant therapy in HER-2 positive breast cancer by inhibiting tumor immune response [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 P5-03-09.
Abstract P5-04-29: Efficacy and safety of low-dose everolimus in Chinese HR-positive, HER2-negative metastatic breast cancer patients
Authors: Shao X , Wang X , Chen Z , Zheng Y 
Published: May 2019

Abstract
Background: Everolimus has been testified to be effective among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, everolimus at dose of 10mg was accompanied by a higher incidence of mTOR-inhibitor class-effect adverse events (AEs) which usually leading to dose reduction or interruption. Additionally, some studies suggested that there was no correlation between dose intensity (5 vs. 10 mg labeled dose) and efficacy. Consequently, we conducted the present study aiming to explore the efficacy and safety of everolimus at dose of 5 mg plus endocrine therapy in Chinese population.
Methods: 68 HR+/HER2- MBC patients were included in this exploratory study who received everolimus at the dose of 5mg in Zhejiang Cancer Hospital between September 2014 and September 2017. Progression free survival(PFS) and overall survival(OS) were estimated by the Kaplan- Meier method, and the hazard ratios(HRs) and corresponding 95% confidence intervals(CIs) were estimated using the Cox proportional harzard model. Besides, objective response rate(ORR), clinical benefitrate(CBR) and safety profile were also evaluated.
Results: After a median follow up of 14 months, PFS was 5.3 months (95%CI 4.2-6.4), and OS was immature. 16(23.5%) were at the first or second-line, 52(76.5%) were at third-line or later. PFS for the first and second-line is significantly longer than that for the third-line or later (12.9 months vs. 4.6 months, P=0.009, HR=0.395, 95% CI=0.192-0.811). 11(16.2%) achieved partial response (PR), 42(61.7%) had stable disease (SD), and 15(22.1%) reported progressive disease (PD). The ORR and CBR were 16.2%, 35.2%, respectively. Most common all grade adverse events were stomatitis(26.5%), fatigue(10.0%), infection(11.8%), thrombocytopenia(5.9%), anemia(4.4%), hyperglycemia(4.4%). The most common ≥3 grade adverse events were stomatitis(4.4 %), infection(2.2%) and thrombocytopenia(1.1%).
Conclusions: The combination of low-dose everolimus and endocrine therapy was highly effective especially at the earlier line in Chinese population. And the safety profiles were similar to previous studies but the incidences were greatly lower. The combination of low-dose everolimus and endocrine therapy may become a proper option for HR+/HER2- MBC.
Citation Format: Shao X, Wang X, Chen Z, Zheng Y. Efficacy and safety of low-dose everolimus in Chinese HR-positive, HER2-negative metastatic breast cancer patients [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 P5-04-29.
Abstract P5-07-09: Withdrawn
Authors: Ahirwar DK , Nasser MW , Shukla RK , Shilo K , Ganju RK 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Ahirwar DK, Nasser MW, Shukla RK, Shilo K, Ganju RK. Withdrawn [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 P5-07-09.
Abstract P5-07-16: Role of collagen X in enhancing the metastatic potential of breast cancer cells using a MDA-MB-231 cell line model
Authors: McKiernan K , Jimenez H , McEachern M , Hubbard J , O'Connell M 
Published: May 2019

Abstract
Breast cancer is the second highest cause of cancer related deaths for women in developed countries. Breast cancer patients with distant metastasis at the time of diagnosis have an estimated 5-year relative survival rate of 26% as compared to a 99% survival rate of patients who have localized tumors. Evidence suggests that collagens play a role in enhancing the metastatic capability of breast cancer cells. Short chain collagen, collagen X, is encoded by the collagen type x alpha 1 chain (COL10A1) gene and is normally expressed exclusively by hypertrophic chondrocytes during endochondral ossification. Recently, COL10A1 gene expression has been found to be overexpressed in various tumor types, including breast tumors. It is hypothesized that an increase in COL10A1 expression may play a role in breast cancer metastasis. The goal of our project was to evaluate the role of collagen X in breast cancer metastasis using the MDA-MB-231 breast cancer cell line. Stable cell lines were generated to express either GFP only (MDA-VEC) or GFP tagged COL10A1 (MDA-COL). GFP and COL10A1 transcript and protein levels were examined to confirm overexpression of collagen X and transwell assays were used to determine changes in the invasive capability of the cells. Cells overexpressing collagen X demonstrated a higher rate of invasion suggesting that collagen X may play a role in enhancing the metastatic potential of breast cancer cells. Understanding the role collagen X plays in breast cancer metastasis may provide a mechanism for developing diagnostic and prognostic strategies for identifying patients whose breast cancer is more prone to metastasize.
Citation Format: McKiernan K, Jimenez H, McEachern M, Hubbard J, O'Connell M. Role of collagen X in enhancing the metastatic potential of breast cancer cells using a MDA-MB-231 cell line model [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 P5-07-16.
Abstract P5-09-12: Germline mutation in TP53 gene in a cohort of 2,561 Chinese high-risk breast cancer patients using multigene panel testing
Authors: Kwong A , Shin V , Au CH , Ho C , Slavin T , Weitzel J , Chan TL , Ma E 
Published: May 2019

Abstract
Background: Li-Fraumeni syndrome (LFS) is a rare autosomal genetic disorder with germline TP53 mutations. Patients with TP53 mutations have a higher risk of developing breast cancer than those harboring BRCA mutations. Although limited studies have shown that TP53 mutation carriers are less responsive to low dose radiation and more susceptible to induce new malignancies from radiotherapy. Moreover screening strategies allows early detection of a spectrum of cancers related to TP53 mutations. From work of BRCA mutations where over 40% novel mutations were detected in Chinese cohort, it is important to evaluate the frequency of TP53 mutation in Chinese to better understand the spectrum to guide appropriate clinical management of these high risk individuals.
Methods: TP53 gene mutation screening was performed on 2,561 high-risk breast cancer patients using multigene panel testing. The patients were accrued by Hong Kong Hereditary and High Risk Breast Cancer Program from March 2007 to May 2018. All detected pathogenic mutations were further validated by bi-directional DNA sequencing and analyzed by our in-house developed bioinformatics pipeline.
Results: Sixteen distinct pathogenic or likely pathogenic variants were identified, and 3 of them were de novo TP53 mutations (18.75%). The mean age of patients who harbored TP53 mutation was 30.44 years (range 18-44), and 50% of the tumors were bilateral breast cancer. Of sixteen different pathogenic mutations, majority of them were missense mutation (87.5%), and 2 were nonsense mutation (12.5%). Four of the sixteen TP53 mutation carriers had family history of breast cancer, while others had a family history of lung cancer (43.75%).
Conclusion: This study revealed that seven patients were found to habor TP53 mutation even when they did not meet the criteria of LFS of LFS-like phenotype, implicated the importance of using multigene panel test for probands and their relatives to offer a comprehensive surveillance programe for TP53 carriers.
Citation Format: Kwong A, Shin V, Au CH, Ho C, Slavin T, Weitzel J, Chan TL, Ma E. Germline mutation in TP53 gene in a cohort of 2,561 Chinese high-risk breast cancer patients using multigene panel testing [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 P5-09-12.
Abstract P5-10-01: Using whole genome sequencing and somatic mutation signatures to unravel insight into familial breast cancer aetiology
Authors: Simpson P , Nones K , Johnson J , Newell F , Patch A-M , Thorne H , Kazakoff S , De Luca X , Parsons M , Ferguson K , Reid L , McCart Reed A , Srihari S , Lakis V , Davidson A , Mukhopadhyay P , Holmes O , Xu Q , Wood S , Leonard C , Beasley J , Degasperi A , Nik-Zainal S , Ragan M , Spurdle A , Khanna KK , Lakhani S , Pearson J , Chenevix-Trench G , Waddell N 
Published: May 2019

Abstract
Approximately 10-15% of breast cancers are associated with a strong family history of disease. Pathogenic variants in BRCA1, BRCA2 or other moderate to highly penetrant susceptibility genes (e.g. TP53, ATM, CHEK2, PALB2 and PTEN) account for a number of breast cancer families. However, for over 50% of families the underlying genetic contribution to their risk remains unknown (termed here as non-BRCA1/2). This has a profound impact for how individuals and their families are managed in the clinic. We applied whole genome sequencing (WGS) to determine whether somatic mutation analysis can reveal insight into the aetiology of familial breast cancer. The full repertoire of somatic mutations was evaluated in 26 BRCA1, 22 BRCA2 and 32 non-BRCA1/2 tumours; including SNPs, indels, copy number changes and structural rearrangements, and mutational signatures. Genomes were also analysed using the HRD Index and HRDetect, as predictors of homologous recombination deficiency. BRCA1, BRCA2 and non-BRCA1/2 tumours exhibited a different burden of mutations, a different spectrum of mutational signatures and different telomere length. Based on collective patterns of mutation signatures, tumours were classified as 'BRCA1-like', 'BRCA2-like' or 'non-BRCA1/2-like' with a 15% rate of tumour re-classification from their original clinical BRCA status. The results demonstrate the power of WGS to differentiate between BRCA1 and BRCA2 driven tumours; in the identification of double-pathogenic germline mutation carriers based on the resulting somatic mutation signature; and in the interpretation of BRCA unclassified variants. WGS of tumour genomes reveals fascinating insights into tumour aetiology and could compliment current genetic testing of breast cancer families.
Citation Format: Simpson P, Nones K, Johnson J, Newell F, Patch A-M, Thorne H, Kazakoff S, De Luca X, Parsons M, Ferguson K, Reid L, McCart Reed A, Srihari S, Lakis V, Davidson A, Mukhopadhyay P, Holmes O, Xu Q, Wood S, Leonard C, Beasley J, Degasperi A, Nik-Zainal S, Ragan M, Spurdle A, Khanna KK, Lakhani S, Pearson J, Chenevix-Trench G, Waddell N. Using whole genome sequencing and somatic mutation signatures to unravel insight into familial breast cancer aetiology [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 P5-10-01.