bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-09-10: Pathological complete response to neoadjuvant trastuzumab is dependent on HER2/CEP17 ratio in HER2-amplified early breast cancer
Authors: Singer CF , Tan YY , Fitzal F , Steger GG , Egle D , Reiner A , Rudas M , Gruber C , Bartsch R , Fridrik M , Seifert M , Exner R , Balic M , Bago-Horvath Z , Filipits M , Gnant M ,   For the Austrian Breast and Colorectal Cancer Study Group
Published: May 2019

Abstract
Purpose To evaluate whether pathological complete response to neoadjuvant trastuzumab is dependent on the level of HER2 amplification.
Patients and Methods 114 women with HER2-overexpressing early breast cancer who had received neo-adjuvant trastuzumab in the prospective ABCSG-24 and ABCSG-32 trials, and for whom the HER2/CEP17 ratio was available, were included in this analysis. The ratio was correlated with tumor response as measured by the three most commonly used definitions of pathological complete response: ypT0 ypN0, ypT0/is ypN0, and ypT0/is.
Results In trastuzumab-treated patients, ypT0 pN0 was achieved in 69.0% of patients with a HER2/CEP17 ratio of &gt;6, but only in 30.4% of tumors with a ratio of ≤6 (p=0.001, Chi Square test). When pCR was defined by ypT0/is pN0 or by ypTis, 75.9% and 82.8% of tumors with a high ratio had a complete remission, while only 39.1%, and 38.3% with a low ratio achieved a pCR (p=0.002 and p&lt;0.001, respectively). Logistic regression revealed that tumors with a higher HER2/CEP17 ratio had a significantly higher probability to achieve ypT0 ypN0 (OR: 5.08, 95% CI 1.86-13.90; p=0.002) than tumors with a low ratio, while none of the other clinicopathological parameters was predictive of pCR. The association between high HER2 amplification and pCR was almost exclusively confined to HR positive tumors (62.5% vs. 24.0%, 75.0% vs. 28.0%, and 87.5% vs. 28.0%, for ypT0 ypN0, ypT0/is ypN0, and ypT0/is; p=0.014, p=0.005, and p&lt;0.001), and was largely absent in HR negative tumors.
Conclusion A HER2/CEP17 ratio of &gt;6 in the pre-therapeutic tumor biopsy is associated with a significantly higher pCR rate particularly in HER2 / HR co-positive tumors, and can be used to predict outcome before neoadjuvant trastuzumab is initiated.
Citation Format: Singer CF, Tan YY, Fitzal F, Steger GG, Egle D, Reiner A, Rudas M, Gruber C, Bartsch R, Fridrik M, Seifert M, Exner R, Balic M, Bago-Horvath Z, Filipits M, Gnant M, For the Austrian Breast and Colorectal Cancer Study Group. Pathological complete response to neoadjuvant trastuzumab is dependent on HER2/CEP17 ratio in HER2-amplified early 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 P1-09-10.
Abstract P2-05-24: Prognostic value of circulating PIK3CA mutations revealed with digital PCR in patients with HER2-positive advanced breast cancer: Results of West Japan Oncology Group study 6110BTR
Authors: Tsurutani J , Sakai K , Takao T , Kimura H , Kawabata H , Tanaka K , Takahashi M , Ito Y , Takao S , Aogi K , Sato K , Tsuji Y , Yamanaka T , Nakanishi Y , Saeki T , Nishio K 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Abstract P2-05-32: Tissue kallikrein-related peptidase 4, a novel biomarker in triple-negative breast cancer
Authors: Dorn J , Yang F , Aubele M , Kiechle M , Schmitt M 
Published: May 2019

Abstract
Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors estrogen receptor and progesterone receptor and not overexpressing the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded triple-negative breast cancer (TNBC) tumor tissue specimens. For this, KLK4 protein expression was assessed by immunohistochemistry in primary tumor tissue sections (tissue microarrays) of 188 TNBC patients, mainly treated with anthracycline- or CMF-based polychemotherapy. KLK4 protein is localized in the cytoplasm of tumor cells and that of accessory stroma cells. In this patient cohort, elevated stroma KLK4 expression, but not tumor cell expression, is predictive for poor disease-free survival by univariate analysis (hazard ratio: 2.26, p=0.001) and multivariable analysis (hazard ratio: 2.12, p&lt;0.01). Likewise, univariate analysis revealed a trend for statistical significance of elevated KLK4 stroma cell expression for overall survival of TNBC patients as well.
Citation Format: Dorn J, Yang F, Aubele M, Kiechle M, Schmitt M. Tissue kallikrein-related peptidase 4, a novel biomarker in 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 P2-05-32.
Abstract P2-06-03: The 3′UTR signature defines a highly metastatic subgroup of triple-negative breast cancer
Authors: Wang L , Hu X , Wang P , Shao Z-M 
Published: May 2019

Abstract
Purpose. Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with an aggressive clinical course. TNBC relapse or metastasis is associated with an unfavorable prognosis so predictive models are needed to chart potential patient outcomes. Alternative polyadenylation (APA) has recently gained attention as a major player influencing the kinetics of gene regulation under diverse physiological and pathological status, resulting in the dynamic usage of 3′ untranslated region (3′UTR). We postulate that alternative 3′UTR patterns, if incorporated into a single model, could improve postoperative risk stratification and identify a highly metastatic subgroup of TNBC. In this study, we used alternative 3′UTR patterns to improve postoperative risk stratification.
Experimental Design. We collected 327 publicly available microarrays and randomly stratified samples in a training (n = 164) and validation set (n = 163). Then, 1,933 3′UTRs were generated based on expression ratios of alternative 3′UTR. After initial feature filtering, we built a 17-3′UTR-based classifier using an elastic net model and validated the prognostic accuracy in both training and validation sets.
Results. Time-dependent ROC comparisons and Kaplan–Meier analyses confirmed an outstanding discriminating power of our prognostic model for TNBC patients. In the training cohort, 5-year event-free survival (EFS) was 78.6% (95% CI 71.2–86.0) for the low-risk group, and16.3%(95% CI 2.3–30.4) for the high-risk group (log-rank p &lt; 0.0001; hazard ratio [HR] 8.29, 95% CI 4.78–14.4), In the validation set, 5-year EFS was 75.6% (95% CI 68.0–83.2) for the low-risk group, and 33.2% (95% CI 17.1–49.3) for the high-risk group (log-rank p &lt; 0.0001; HR 3.17, 95% CI 1.66–5.42). The 17-3′UTR-based classifier could be used to independently predict outcomes and this outperformed prognosis using classical clinicopathological risk factors.
Conclusions. Our 17-3′UTR-based classifier provides a superior prognostic performance for estimating disease recurrence and metastasis in TNBC patients and it may permit personalized management strategies.
Citation Format: Wang L, Hu X, Wang P, Shao Z-M. The 3′UTR signature defines a highly metastatic subgroup of 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 P2-06-03.
Abstract P3-04-17: Global transcriptional repression by the coactivator SRC-1 mediates disease progression in treatment-resistant breast cancer
Authors: Ward E , Varešlija D , Fagan A , Hill A , Young L 
Published: May 2019

Abstract
Despite the effectiveness of endocrine therapy in treating estrogen receptor (ER) positive breast cancer, nearly 40% of breast cancer patients may develop resistance which can lead to metastatic disease progression. Steroid receptor co-activator-1 (SRC-1), a key regulator of ER signalling, is overexpressed in 35% of breast cancer patients and is strongly associated with the development of endocrine resistant metastasis(1). Recent studies highlighted the ability of SRC-1 to also act as transcriptional repressor. SRC-1 can therefore bi-directionally regulate gene expression to promote the resistant phenotype (2).
This study employed a genome-wide multi-omics sequencing approach to determine the SRC-1 repression signature in endocrine resistance and elucidate the mechanism by which SRC-1 mediates this repression. RNA-sequencing identified 736 genes significantly downregulated by SRC-1, with common functional pathways such as differentiation, cell morphogenesis and extracellular matrix enriched in the gene set. Parallel global methylation sequencing analysis revealed distinct differentially methylated regions specific to SRC-1 repressed target genes. Mechanistic studies in endocrine resistant cells revealed a role for methylation proteins, DNMTs and MBD, in SRC-1 directed repression. Through combined analysis of our global sequencing data we identified a network hub of five differentiation genes directly repressed by SRC-1. High expression of this signature predicts enhanced recurrence free survival in tamoxifen treated patients (n=335, p=0.032). A reduction in expression of these genes was shown to have functional output on proliferation, migration and mammosphere formation. Finally, we use tumour explant models to show that targeting DNA methylation can be used to reverse the SRC-1 driven suppression of this differentiation hub.
Here we report a novel mechanism by which SRC-1 may be driving endocrine resistant tumorigenesis. Our genome-wide discovery approach revealed a global epigenetic re-programming pathway whereby concerted differential DNA methylation is potentiated by the activation of SRC-1 in the presence of tamoxifen in the endocrine resistant setting. This study suggests that therapeutic strategies of combined targeted epigenetic therapy with estrogen deprivation could be a successful strategy to prevent acquired resistance to endocrine therapy.
Citation Format: Ward E, Varešlija D, Fagan A, Hill A, Young L. Global transcriptional repression by the coactivator SRC-1 mediates disease progression in treatment-resistant 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 P3-04-17.
Abstract P4-15-01: Cost-effectiveness of pre-implantation genetic diagnosis for BRCA mutation carriers
Authors: Lipton JH , Wong WWL , Warner E , Greenblatt EM , Lee EK , Chan KKW 
Published: May 2019

Abstract
Introduction: Management of BRCA mutation carriers is very expensive due to preventive surgeries and/or screening tests, as well as greater likelihood of cancer treatment. The related cancer burden and costs continue from generation to generation. One relatively new option for male or female BRCA mutation carriers, who wish to have children, is pre-implantation genetic diagnosis (PGD) of in vitro fertilized embryos. PGD eliminates the mutation from the descendants of these carriers. The purpose of this study was to model the cost-effectiveness of PGD.
Methods: We developed a Markov Model using TreeAge Pro 2016 and compared incidence of cancers, cancers-related death, costs, quality adjusted life-years (QALY), and incremental cost-effectiveness ratio (ICER) in the 2nd generation associated with conventional management of BRCA mutation carriers vs. PGD using a U.S. third-party payer's perspective with a lifetime horizon at a discount rate of 3% per year. In the model, health states were implemented to reflect the natural history of breast and ovarian cancer for women, and prostate cancer (and breast cancer in BRCA2 mutation carriers) for men. Model data were obtained from published literature. Costs were determined from published data and insurance payment schedules.
Results: Our preliminary results show that for BRCA1 mutation carriers, the PGD with IVF strategy is associated with an increase of 0.29 QALYs and costs an additional $292.68 per person, translating to an ICER of $1,014.25/QALY when compared with “No PGD”, making it highly cost-effective. For BRCA2 mutation carriers, the PGD with IVF strategy is associated with an increase of 0.17 QALYs and costs an additional $4,916.88 per person, translating to an ICER of $28,436.10/QALY when compared with “No PGD”, making it cost-effective.
Table 1StrategyCost ($)Incr Cost ($)Eff (QALY)Incr Eff (QALY)Incr C/E ($/QALY) BRCA 1 No PGD323,347.22 28.41 PGD323,639.89292.6828.70.291,014.25BRCA 2 No PGD318,723.02 28.52 PGD323,639.894,916.8828.70.1728,436.10
Conclusion: PGD for both BRCA1 and BRCA2 mutation carriers reduces cancer burden, increases QALYs and, is very cost-effective in the 2nd generation cohort, making this an attractive option from the perspectives of patients and public payers. Our estimates are conservative because the cost-effectiveness of PGD will likely improve further if subsequent generations are included in the model, given the expected further reduction in cancer burden and associated cost-savings in subsequent generations.
Citation Format: Lipton JH, Wong WWL, Warner E, Greenblatt EM, Lee EK, Chan KKW. Cost-effectiveness of pre-implantation genetic diagnosis for BRCA mutation carriers [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 P4-15-01.
Abstract P5-09-07: Impact of germinalcenter-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population
Authors: Kotani H , Ito H , Kuwahara K , Kuzushima K , Iwata H , Tsunoda N , Nagino M , Tanaka H , Matsuo K 
Published: May 2019

Abstract
Background: Germinal center-associated nuclear protein (GANP) is a phosphoprotein which is involved in mRNA export and the regulation of DNA recombination. We have previously demonstrated that deficiency of GANP led to spontaneous development of mammary gland tumors in a mouse model. In addition, we found that decreased GANP expression in human breast cancer tissue was an independent prognostic factor. Here, we conducted a case-control study and a retrospective cohort study to investigate whether single nucleotide polymorphisms (SNPs) of GANP are associated with sporadic breast cancer risk and prognosis in a Japanese population.
Subjects and Methods: Six hundred-ninety-four breast cancer cases and 1,376 age- and menopausal status-matched controls were selected within the framework of the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Cases and controls were genotyped using an Infinium iSelect custom array (iCOGS, Illumina Inc., San Diego, CA, USA). We assessed 13 SNPs at the GANP locus, 2 SNPs (rs2839178 and rs11702450) were selected for further analysis by considering linkage disequilibrium. Conditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals. In addition, the survival impact of the two SNPs was retrospectively analyzed using the 694 breast cancer cases. To evaluate the effect of SNPs on overall survival (OS) and disease-free survival (DFS), multivariate Cox proportional hazards modeling was applied.
Results: Compared to the AA genotype of rs2839178, the GG genotype showed statistically significant associations with breast cancer risk (OR: 0.48, 95%CI:0.30–0.76, P = 0.002). In prognostic analysis, compared to those with the genotype AA at rs2839178, patients with AG or GG showed longer DFS (HR: 0.71, 95%CI: 0.49–1.04 and 0.42, 0.13–1.42, respectively, P for trend = 0.04). The GG genotype of rs2839178 also showed a positive tendency for longer OS although it was not statistically significant (HR: 0.69, 95%CI: 0.44–1.08, P = 0.11). We did not find that rs11702450 was associated with either breast cancer risk or prognosis.
Conclusion: This is the first study to investigate the association between GANP SNPs and breast cancer risk and prognosis. The direction of association with DFS was consistent with that of susceptibility. These results demonstrate that GANP SNPs presumably prevent the occurrence and malignant advancement of sporadic breast cancers.
Citation Format: Kotani H, Ito H, Kuwahara K, Kuzushima K, Iwata H, Tsunoda N, Nagino M, Tanaka H, Matsuo K. Impact of germinalcenter-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population [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 P5-09-07.
Abstract P4-01-02: Early detection of residual breast cancer through a robust, scalable and personalized analysis of circulating tumour DNA (ctDNA) antedates overt metastatic recurrence
Authors: Coombes RC , Armstrong A , Ahmed S , Page K , Hastings RK , Salari R , Sethi H , Boydell A-R , Shchegrova SV , Fernandez-Garcia D , Gleason KL , Goddard K , Guttery DS , Assaf ZJ , Balcioglu M , Moore DA , Primrose L , Navarro SL , Aleshin A , Rehman F , Toghill BJ , Louie MC , Zimmermann BG , Lin C-HJ , Shaw JA 
Published: May 2019

Abstract
Background:
Many breast cancer patients relapse after primary treatment but there are no reliable tests to detect distant metastases before they become overt. Here we show earlier identification of recurring patients through a scalable personalised ctDNA analysis. The method is applicable to all patients, and not limited to hot-spot mutations typically detected by gene panels.
Methods:
Forty-nine non-metastatic breast cancer patients were recruited following surgery and adjuvant therapy. Plasma samples (n=208) were serially collected semi-annually. Using the analytically validated SignateraTM workflow, we determined mutational signatures from primary tumour whole exome data and designed personalised assays targeting 16 variants with high sensitivity by ultra-deep sequencing (average &gt;100,000X). The patient-specific assay was used to detect the presence of the mutational signature in the plasma.
Results:
In 16 of 18 (89%) clinically-relapsing patients, ctDNA was detected ahead of metastatic relapse being diagnosed by clinical examination, radiological and biochemical (CA15-3) measurements, and remained ctDNA-positive through follow-up. Of the 2 patients not detected by ctDNA, one had a small local recurrence only (now resected) and the other had three primary tumours. None of the 31 non-relapsing patients were ctDNA-positive at any time point (n=142). Metastatic relapse was predicted by Signatera with high accuracy and a lead time of up to 2 years (median=9.5 months).
Conclusions:
The use of a scalable patient-specific ctDNA-based validated workflow detects breast cancer recurrence ahead of clinical detection. Accurate and earlier prediction by ctDNA analysis could provide a means of monitoring breast cancer patients in need of second-line salvage adjuvant therapy in order to prevent overt life-threatening metastatic progression.
Citation Format: Coombes RC, Armstrong A, Ahmed S, Page K, Hastings RK, Salari R, Sethi H, Boydell A-R, Shchegrova SV, Fernandez-Garcia D, Gleason KL, Goddard K, Guttery DS, Assaf ZJ, Balcioglu M, Moore DA, Primrose L, Navarro SL, Aleshin A, Rehman F, Toghill BJ, Louie MC, Zimmermann BG, Lin C-HJ, Shaw JA. Early detection of residual breast cancer through a robust, scalable and personalized analysis of circulating tumour DNA (ctDNA) antedates overt metastatic recurrence [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 P4-01-02.
Abstract P4-11-02: Subjective and objective assessment of efficacy of frozen gloves and socks to prevent nab-paclitaxel-induced peripheral neuropathy in patients with breast cancer
Authors: Yamashita T , Hattori M , Nakada T , Hayashi T , Kamei K , Tatsuya T , Nagao Y , Mase T , Wada M , Mizuno T , Shimozuma K , Iwata H , Yamaguchi T 
Published: May 2019

Abstract
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent side-effect of taxanes which play a central role in the treatment of breast cancer. CIPN can negatively influence long-term quality of life, warranting the development of effective prevention strategies. This study investigates the efficacy of frozen gloves and socks (FGS) in reducing the incidence and severity of nab-paclitaxel-induced peripheral neuropathy. Endpoints were evaluated using both clinician and patient reports.
Methods: This is a multicenter phase II single arm trial study of the effects of FGS for advanced or metastatic breast cancer patients receiving nab-paclitaxel (260 mg/m2) every 3 weeks. Patients wore FGS on their diseased side hand and foot for 60 min during infusion. The other side acted as the untreated control. CIPN was assessed using Patient Neurotoxicity Questionnaire (PNQ), PRO-CTCAE and CTCAE at baseline and every cycle of nab-paclitaxel. The primary endpoint was the incidence of CIPN assessed by PNQ (grade C or higher) after receipt of up to 4 cycles of nab-paclitaxel.
Results: Between September 2012 and January 2015, 50 patients from 16 sites were enrolled in this study. Of 50 patients, 27 (54%) received at least 4 cycles of nab-paclitaxel. There was a trend for the incidence of CIPN assessed by PNQ and PRO-CTCAE to be lower in the intervention side than in the control side, although this difference was not statistically significant. The incidence of CIPN assessed by CTCAE was significantly lower in the treated hand (Table).
Conclusions: Among breast cancer patients who received nab-paclitaxel, FGS produced favorable effects as detected by reduced clinician-reported CTCAE grades for CIPN, although the study did not detect differences in self-reported symptoms of CIPN using PRO-CTCAE or PNQ. Clinical trial information: UMIN000007907.
Difference according to the evaluation method of CIPN Hands (%) Feet (%) InterventionControlp*InterventionControlp*Patient-Reporting CIPNPNQ (grade C or higher)12190.3416160.63Patient-Reporting CIPNPRO-CTCAE Severity ≥ Moderate13180.0815160.56 Interference ≥ Somewhat7100.328100.32Clinician-Grading CIPNCTCAE (≥ Grade II)15190.0314131.0
*McNemar's test
Citation Format: Yamashita T, Hattori M, Nakada T, Hayashi T, Kamei K, Tatsuya T, Nagao Y, Mase T, Wada M, Mizuno T, Shimozuma K, Iwata H, Yamaguchi T. Subjective and objective assessment of efficacy of frozen gloves and socks to prevent nab-paclitaxel-induced peripheral neuropathy in patients with 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 P4-11-02.