bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-11-10: Impact of disease progression on health-related quality of life in patients with metastatic breast cancer in the PRAEGNANT breast cancer registry
Authors: Wallwiener M , Nabieva N , Haeberle L , Taran FA , Hartkopf AD , Volz B , Overkamp F , Brandl AL , Kolberg H-C , Hadji P , Tesch H , Ettl J , Lux MP , Lueftner D , Belleville E , Fasching PA , Janni W , Beckmann MW , Wimberger P , Hielscher C , Fehm T , Brucker SY , Wallwiener D , Schneeweiss A , Mueller V 
Published: February 2018

Abstract
Background: Improved progression-free survival is considered as treatment goal for patients with metastatic breast cancer (MBC) since it is assumed to delay or prevent deterioration of quality of life.Aim of our analysis was to examine the influence of disease progression on health-related quality of life (HRQoL).
Methods: The PRAEGNANT study comprises a real-life registry for patients with MBC. HRQoL was assessed with the EORTC-QLQ-C30 Version 3.0 questionnaire at study entry and every 3 months thereafter. The primary endpoint was minimally important deterioration (MID) in global HRQoL score by ≥ five points between baseline and any follow-up assessment. A logistic regression model was built with MID (yes/no) at a follow-up timepoint as outcome variable and several covariates as predictors.
Results: In total, 329 patients were included in this analysis, with disease progression in 63 patients. Concerning the primary study aim, progression status predicted MID of global HRQoL status in addition to the other covariates. The adjusted odds ratio for the effect of progression status on MID was 2.22 (95% CI: 1.04 – 4.73). Comparisons of mean differences of QoL domains/scales yielded no differences.
Conclusions: We provide evidence that disease progression in patients with metastatic breast cancer in a real-world registry has a significant negative impact on HRQoL as measured by MID of HRQoL. This study emphasizes the relevance of avoiding progression and prolonging PFS to maintain QoL.
Citation Format: Wallwiener M, Nabieva N, Haeberle L, Taran FA, Hartkopf AD, Volz B, Overkamp F, Brandl AL, Kolberg H-C, Hadji P, Tesch H, Ettl J, Lux MP, Lueftner D, Belleville E, Fasching PA, Janni W, Beckmann MW, Wimberger P, Hielscher C, Fehm T, Brucker SY, Wallwiener D, Schneeweiss A, Mueller V. Impact of disease progression on health-related quality of life in patients with metastatic breast cancer in the PRAEGNANT breast cancer registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-11-10.
Abstract P6-11-18: Ten year trends in antiemetic prescribing in cancer patients receiving highly emetogenic chemotherapy (HEC)
Authors: O'Sullivan CC , Van Houten HK , Sangaralingham L , Leal AD , Shinde S , Liu H , Ettinger D , Loprinzi CL , Ruddy KJ 
Published: February 2018

Abstract
Purpose: Prevention of chemotherapy-induced nausea and vomiting (CINV) is essential to preserve quality of life in cancer patients receiving highly emetogenic chemotherapy (HEC) such as doxorubicin-cyclophosphamide (AC) or cisplatin. Recently, new drugs (e.g. fosaprepitant and newer neurokinin 1 receptor antagonists [NK1RAs], rolapitant and netupitant) and updated guidelines for antiemetic use (e.g. adding olanzapine) have emerged. However, trends in real world antiemetic use are understudied.
Methods: We performed a retrospective study using the OptumLabs Data Warehouse (OLDW), which includes administrative claims for privately insured and Medicare Advantage enrollees in the U.S. We identified 34,236 patients age 18 years or older treated with either AC or cisplatin between January 2006 and June 2016. Data collected included baseline demographics (age, gender, census region and race), chemotherapy administered, and presence/absence of a central intravenous access device. Trends of anti-emetic use were presented overall and separately for 5-HT receptor antagonists (5HT3RAs) and NK1RAs.
Results: 23,030 patients (67.3%) received an anthracycline-based regimen (AC with or without docetaxel or paclitaxel), and 11,206 (32.7%) patients received cisplatin. Approximately two thirds of patients were female (n= 23,392). Dexamethasone use was stable over the decade (used by 85-90% in all years). Use of 5HT3RAs, primarily palonosetron and ondansetron, occurred in at least 95% of patients in all study years, consistent with guideline recommendations. NK1RAs were underutilized early on compared with guideline recommendations, but use increased to approximately 80% in the most recently evaluated year. Fosaprepitant use rose precipitously starting in 2009, preceding a sharp fall in aprepitant use beginning in 2011. The use of olanzapine, rolapitant and netupitant was minimal throughout the study period.
Conclusions: Dexamethasone and 5-HT3RAs were used in the vast majority of patients receiving HEC, in accordance with guideline recommendations. Less compliance with guidelines was seen with NK1RA use.
Citation Format: O'Sullivan CC, Van Houten HK, Sangaralingham L, Leal AD, Shinde S, Liu H, Ettinger D, Loprinzi CL, Ruddy KJ. Ten year trends in antiemetic prescribing in cancer patients receiving highly emetogenic chemotherapy (HEC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-11-18.
Abstract P6-15-05: Randomized controlled trial of neoadjuvant eribulin mesylate versus paclitaxel in women with operable breast cancer (JONIE-3 study)
Authors: Miura D , Hasegawa Y , Ishikawa T , Tachibana A , Horiguchi J , Hayashi M , Miyashita M , Kubota T , Narui K , Suzuki M , Akazawa K , Kohno N 
Published: February 2018

Abstract
Background:
Although treatment of eribulin mesylate (E) improved overall survival in metastatic breast cancer (BC) patients, little is known about the efficacy in early BC. The hypothesis of this study is that sequential administration of E followed by FEC would have less toxic, particularly peripheral neuropathy, and also have similar effect compared to paclitaxel (P) followed by FEC as primary systemic therapy (PST) for woman with operable BC.
Methods:
This is a phase II multicenter open label study (UMIN000012817). Patients (pts) were randomly assigned to either E (1.4mg/m2, d1 and d8, q21 days, 4 cycles) + FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) or P (80mg/m2, weekly, 12 cycles) + FEC as PST. HER2+ patients were allowed to receive trastuzumab. Stratification factors were ER, HER2, and menopausal status. Primary endpoint was the incidence of peripheral sensory and motor neuropathy (PSN and PMN) with Grade 1 or higher according to CTCAE ver.4.0. Secondary endpoints were pathological complete response (pCR) rates (ypT0/is/ypN0), clinical response rates (CR+PR), and adverse events. Safety was assessed in all pts who received at least one dose of the study drug.
Results:
Between 12/2013 to 3/2016, 121 pts were randomly assigned equally to E + FEC and P + FEC. Excluding 5 pts from the primary assessment, 116 pts (58 in each group) were included in the full analysis set. The characteristics of the pts were similar in the two arms. At the end of E or P administration, the incidences of PSN were 55.4% and 92.9% in E and P arm, respectively (p&lt;0.001). The incidences of PMN were 25.9% and 44.9% in E and P arm, respectively (p=0.049). At the end of E or P + FEC, PSN accounts for 38.9% in E arm and 85.2% in P arm (p&lt;0.001), and PMN accounts for 20.7% in E arm and 32.8% in P arm (p=0.201). The pCR rates in E and P arm were 20.7% and 29.8% (p=0.092). The clinical response rates in E and P arm were 82.2% and 91.0% (p=0.108). No statistical significant difference was found in efficacy of PST between E and P.
Conclusion:
This randomized phase II study revealed that eribulin had favorable peripheral neuropathy profile with modest efficacy in the neoadjuvant setting, compared with paclitaxel.
Citation Format: Miura D, Hasegawa Y, Ishikawa T, Tachibana A, Horiguchi J, Hayashi M, Miyashita M, Kubota T, Narui K, Suzuki M, Akazawa K, Kohno N. Randomized controlled trial of neoadjuvant eribulin mesylate versus paclitaxel in women with operable breast cancer (JONIE-3 study) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-05.
Abstract PD1-01: Triple negative breast cancer predisposition genes
Authors: Couch FJ , Shimelis H , LaDuca H , Hu C , Hart SN , Polley EC , Pesaran T , Tippin-Davis B , Goldgar DE , Dolinsky JS 
Published: February 2018

Abstract
Background: Germline cancer testing panels provide an effective method for identifying individuals at increased risk for breast cancer. However, estimates of risk for triple negative breast cancer (TNBC) (estrogen receptor-negative, progesterone receptor-negative, HER2-negative) associated with pathogenic mutations in panel genes have not been established. We sought to define the genes that contribute to TNBC.
Methods:Germline hereditary cancer multigene panel testing results were obtained for 8,753 TNBCs evaluated by a clinical testing laboratory. Associations between pathogenic mutations in individual genes and TNBC were assessed by comparing mutation frequencies in TNBCs and in the Exome Aggregation Consortium, non-Finn European, non-Cancer Genome Atlas reference controls.
Results: Inactivating mutations in 21 known cancer predisposition genes were identified in 14.6% of TNBCs. BRCA1, BRCA2, PALB2, BARD1, and RAD51D alterations were associated with high risks (odds ratio(OR)&gt;5.0) of TNBC and variants in BRIP1, RAD51C, MSH6, and TP53 were associated with moderate risks (OR&gt;2). In contrast, ATM, CHEK2, NBN, and RAD50 yielded no clinically relevant risks of TNBC. Pathogenic mutations in these established non-BRCA1/2 TNBC susceptibility genes were detected in 6.3% of TNBCs. Similar trends were observed among African American TNBCs. Overall, 5.5% of TNBCs with pathogenic mutations did not meet NCCN clinical testing criteria for BRCA1/2 due to a lack of significant family history and diagnosis over the age of 60.
Conclusions: The identification of genes associated with elevated risk of TNBC will improve understanding of the etiology of this aggressive form of breast cancer and inform risk management of individuals receiving panel testing. The high frequency of pathogenic variants suggests that all patients with TNBC, regardless of age of diagnosis or family history of cancer, should be considered for multigene panel testing.
Citation Format: Couch FJ, Shimelis H, LaDuca H, Hu C, Hart SN, Polley EC, Pesaran T, Tippin-Davis B, Goldgar DE, Dolinsky JS. Triple negative breast cancer predisposition genes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD1-01.
Abstract PD1-05: Transgenerational epigenetic silencing of BRCA1 due to a germline variant unmasks a new mechanism for familial breast and ovarian cancer
Authors: van Veen EM , Smith MJ , Byers HJ , Wallace AJ , Lalloo FI , Newman WG , Evans DGR 
Published: February 2018

Abstract
In families with multiple affected individuals with early-onset breast/ovarian cancer pathogenic variants in BRCA1 or BRCA2 are identified in approximately 20% of the cases. Extensive efforts have been made to identify additional highly penetrant breast cancer genes or alternative mutational mechanisms affecting BRCA1 and BRCA2 to explain the missing heritability. It has been proposed that part of the missing heritability may be explained by gene silencing due to promoter methylation of cancer associated genes, as described in colorectal cancer (MLH1 and MSH2). Here, for the first time, we report two independent families with multiple individuals affected by breast and ovarian cancer with transgenerational promoter methylation of BRCA1.
RNA analysis of BRCA1 in the germline of breast/ovarian families, previously found to be BRCA1/2 mutation negative by Sanger sequencing and copy number analysis, identified two families with allelic loss of expression. To investigate the mechanism of transcriptional silencing, a total of 14 affected and unaffected family members from these two families were tested for BRCA1 promoter methylation by pyrosequencing in blood, buccal, and hair follicle cells. Allele specific methylation was determined by clonal bisulphite sequencing.
BRCA1 promoter methylation in all three germ layers was present in 11 of 14 family members. Of the 7 women with promoter methylation five were affected with grade 3 breast/high grade serous ovarian cancer. The four males with BRCA1 promoter methylation had no history of cancer. Methylation levels were ˜50%, consistent with the silencing of one allele detected in RNA in these family members. Clonal bisulphite sequencing of an affected family member of each family confirmed that the alternative allele was specifically methylated. Interestingly, in both families the methylation pattern of the BRCA1 promoter segregated with the same novel heterozygous variant in the 5'UTR of BRCA1.
These results indicate a novel mechanism for familial breast/ovarian cancer, caused by epigenetic silencing of one allele by transgenerational hypermethylation of the BRCA1 promoter, secondary to a variant in cis of BRCA1. We propose that methylation analyses are indicated in all families affected by early onset breast/ovarian cancer where standard mutation screening of BRCA1/2 has not identified a causative variant.
Citation Format: van Veen EM, Smith MJ, Byers HJ, Wallace AJ, Lalloo FI, Newman WG, Evans DGR. Transgenerational epigenetic silencing of BRCA1 due to a germline variant unmasks a new mechanism for familial breast and ovarian cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD1-05.
Abstract PD4-01: The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ breast cancer
Authors: Mao P , Kusiel J , Cohen O , Wagle N 
Published: February 2018

Abstract
Approximately 70% of breast cancers express the estrogen receptor (ER), and estrogen signaling drives breast cancer cell growth and progression. ER-directed therapies are commonly used to treat ER+ breast cancer and have improved survival for patients, yet resistance to those therapies inevitably occurs. Mutations in the estrogen receptor itself occur in ∼25-30% of patients with ER+ metastatic breast cancer that has developed resistance to aromatase inhibitors. Beyond these ER mutations, other resistance mechanisms are not well described. Moreover, clinical mechanisms of resistance to another class of ER-targeted agents, selective estrogen receptor degraders (SERDs), such as fulvestrant have not been clearly identified.
Here we report two FGFR2 mutations identified in patients with resistant ER+ metastatic breast cancer, N550K and M538I. N550K is a well-known activating FGFR2 mutation; M538I stabilizes the active kinase conformation and it has not previously been described in breast cancer. When expressed in ER+ T47D cells, FGFR2 M538I and N550K led to resistance to fulvestrant, and the CDK4/6 inhibitor palbociclib and the combination of the two agents. FGFR2 M538I induced hyperactivity of p-FRS2, p-ERK and p-AKT, which is higher than wildtype FGFR2 and comparable to other known activating mutations N550K and K660N.
In addition, overexpression of M538I mutant reduced sensitivity to FGFR inhibitors PD173074 and dovitinib in T47D cells, suggesting M538I is also functionally activating. Due to the hyperactive downstream signaling elicited by the mutation, cells overexpressing FGFR2 M538I achieved optimal growth in the presence of low dose of FGFR inhibitor. Under such conditions, FGFR2 M538I conferred more potent resistance to fulvestrant as compared to wildtype FGFR2. However, drug resistance resulting from M538I mutant can be fully resensitized to fulvestrant and/or palbociclib with high dose of FGFR inhibitors.
In summary, we have identified activating FGFR2 mutations (M538I and N550K) in ER+ breast cancer patients, which may contribute to the development of resistance to SERDs and CDK4/6 inhibitors. Additional FGFR2 mutations have been recently identified in other cohorts of patients with resistant ER+ metastatic breast cancer, suggesting that this may be a clinical mechanism of resistance in some patients. Patients with activating FGFR2 mutations may benefit from the treatment with an FGFR inhibitor in combination with SERDs and CDK4/6 inhibitors.
Citation Format: Mao P, Kusiel J, Cohen O, Wagle N. The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD4-01.
Abstract PD5-02: Not presented
Authors: Guerrero-Zotano AL , Stricker TP , Hutchinson KE , Stover DG , Formisano L , Lee K-M , Schwarz LJ , Giltnane JM , Jansen VM , Gavila J , Perez-Fidalgo A , Lluch A , Llombart A , Bayar MA , Michiels S , André F , Arnedos M , Ruiz A , Arteaga CL 
Published: February 2018

Abstract
This abstract was not presented at the symposium.
Abstract PD5-11: Not presented
Authors: Bardia A , Yardley DA , Hurvitz S , Wright G , Moroose R , Ma C , Hart L , Tan-Chiu E , Blau S , Sanft T , Dichmann R , Zelnak A , DeMichele A , Clark A , Small T , Tucci C , Samant TS , Purkayastha D , Karuturi M , Moulder S 
Published: February 2018

Abstract
This abstract was not presented at the symposium.
Abstract PD7-04: Contribution of radiation therapy to the overall cost of cancer care for clinical stage IA breast cancer patients
Authors: Dvorak T , Coltey D , Waters J , Kelly P , Buchholz D 
Published: February 2018

Abstract
Background: Cost of cancer care continues to rise and there is an increasing interest in episode-of-care and bundled payments. Radiation therapy is a well-established component of clinical Stage IA breast cancer care. However, the contribution of radiation to the cost of breast cancer care is not well understood. We were interested in evaluating the contribution of radiation cost to our overall Cancer Center breast cancer care cost, by using revenue received as a proxy.
Methods: Patients with clinical Stage IA breast cancer managed completely at our Cancer Center between 1/1/2014 and 12/31/2014 were identified from cancer registry. An IRB-approved retrospective review of clinical charts and financial data of patients was performed. Individual chart review identified whether and which kind of surgery, chemotherapy, and radiation therapy was delivered. Financial review identified actual technical revenue received for 365 days after the date of first contact, and apportioned it accordingly to the various cost centers, including radiation oncology. All patients were included regardless whether they were Commercial, Medicare, Medicaid, self-pay, or free-care.
Results: There were 110 patients treated with clinical Stage IA breast cancer. All patients (100%) underwent surgery (lumpectomy 69%; mastectomy 5%, mastectomy with reconstruction 26%). Chemotherapy was delivered in 20% of patients (neoadjuvant 13%; adjuvant 7%). Seventy seven percent saw a radiation oncologist, and 57% received radiation therapy. Radiation technique was 3D in 92% and IMRT in 8%. Fractionation was conventional in 55%, accelerated in 43%, and APBI in 2%. Most common treatment pathways were lumpectomy with radiation (46%), mastectomy with reconstruction alone (18%), and lumpectomy alone (14%). Concordance with national guidelines was ≥90%. Overall cost of care for these patients was $6.3 million. Medicare accounted for 35% of patients. Radiation cost was $1.1 million (17%), compared with $2.1 million (33%) for surgery, $2.4 million (38%) for chemotherapy, and $0.7 million for other costs (imaging, lab, ED visits, etc).
Conclusions: Radiation therapy was used in ˜60% of clinical Stage IA patients, but accounted for only ˜20% of the overall cost to the health care system. Given the demonstrated survival benefit of radiation therapy in the care of breast cancer patients, and our high concordance with national guidelines, radiation therapy in our Cancer Center provides high value to our patients, as we move toward value-based episodes of care.
Citation Format: Dvorak T, Coltey D, Waters J, Kelly P, Buchholz D. Contribution of radiation therapy to the overall cost of cancer care for clinical stage IA breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-04.
Abstract PD8-02: Mechanisms of recurrence: Paired analysis of primary and metastatic triple negative breast cancer
Authors: Zhao Z-M , Yost S , Yuan Y-C , Warden C , Chuang J , Yuan Y 
Published: February 2018

Abstract
Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of invasive breast cancer that lacks ER, PR, and HER2 expression. It is a heterogeneous disease with several molecular subtypes: basal-like1 (BL-1), basal-like 2 (BL-2), mesenchymal (M), and luminal androgen receptor (LAR). Treatment for TNBC is normally limited to chemotherapy, and relapse is common. Here we report molecular alterations associated with TNBC metastasis by analyzing the genomic profiles of paired primary and metastatic TNBCs.
Methods:50 paired TNBCs were identified through an IRB-approved protocol via the City of Hope (COH) Biospecimen Repository. DNA mutation and mRNA expression profiles of 10 paired primary and metastatic TNBCs were analyzed. DNA mutations were identified using exome sequencing by FoundationOne®. Affymetrix Human Genechip 2.0 was used for mRNA expression profiling. Raw data were normalized and processed using Expression Console, and linear regression was performed using Limma to identify the differentially expressed genes between primary and metastatic TNBCs.
Results: DNA mutation profiling showed that multiple mutations occurred within genes covering pathways of PI3K/AKT/mTOR, DNA repair, RAS/MAPK, cell cycle, and growth factor receptor signaling, reconfirming genomic heterogeneity of TNBCs. Gene expression profiles were analyzed for Lehmann's TNBC molecular subtypes (BL-1, BL-2, M, and LAR). Six of ten TNBCs showed phenotype shift between the primary and metastatic TNBCs. Several unique gene expression patterns were identified by comparing the paired TNBCs. CCNE1 and TPX2 were co-overexpressed in metastatic TNBCs compared to paired primaries. This mirrored prior studies in ovarian cancer, where co-overexpression of CCNE1 and TPX2 were found related to clonal resistance against chemotherapy. Splicing factors TRA2B and SRSF7 were also over-expressed in metastatic TNBCs compared with primaries. The analysis studying the association of CCNE1 and TPX2 with overall survival is ongoing using TCGA.
Conclusion: Overall, these results show the comparative changes between primary and relapsed TNBCs and indicate the heterogeneity of molecular mechanisms of recurrence. CNNE1 and TPX2 may represent important genes involved in TNBC metastasis. Further analyses including a total of 50 paired TNBCs are currently underway.
Study Contact: Yuan Yuan MD PhD, City of Hope Comprehensive Cancer Center; Duarte, CA 91030; Email: yuyuan@coh.org
Citation Format: Zhao Z-M, Yost S, Yuan Y-C, Warden C, Chuang J, Yuan Y. Mechanisms of recurrence: Paired analysis of primary and metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD8-02.