bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract MS2-2: Missed opportunities - The perils of under-treatment
Authors: Freedman R 
Published: May 2019

Abstract
Although we have seen improvements in breast cancer survival over time, the pace of improvement has varied among patients with breast cancer, and disparities in breast cancer outcomes have widened for some sub-groups. In particular, black women, those without easy access to medical care, and those at the extremes of age (youngest and oldest patients), are at higher risk for sub-optimal treatment and consequent sub-optimal breast cancer outcomes. These disparities have evolved during an era of significant treatment advances in breast cancer such as hormonal therapy and HER2-directed therapy, with a concern that under-treatment has contributed to differences in breast cancer-specific survival. Though there are cases when over-treatment and over-diagnosis result in undue toxicity, worsened quality of life, and possible detrimental outcomes, there are also many cases where patients are simply under-treated. This under-treatment manifests in a number of ways, and not only in a lack of treatment receipt all together, but also in receipt of lower intensity, non-standard, delayed, or incomplete treatment, which may be most apparent in the setting of longer-term treatments such as hormonal therapy or maintenance HER2-directed therapy. The reasons for under-treatment are complex, highly variable, and may include clear and appropriate medical contraindications but also poor treatment adherence, social stressors which limit treatment completion, the high cost of care, and limited access to high-quality care. In addition, under-treatment likely occurs due to a lack of available prospective evidence to support ideal treatments in different patient sub-groups with the need to uncomfortably extrapolate and apply data from clinical trials where many subgroups are under-represented. We need to urgently improve the evidence base for populations at risk for under-treatment so that we can better understand the side effects and outcomes experienced for both standard treatments and alternative treatment strategies. We will never realize improved survival from breast cancer for all patients until we can assure that each patient is individually receiving the right therapy at the right time with the right amount and for the right duration.
Citation Format: Freedman R. Missed opportunities - The perils of under-treatment [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 MS2-2.
Abstract OT2-07-08: Withdrawn
Authors: Paplomata E , Borges V , Loi S , Abramson V , Hamilton E , Hurvitz S , Lin N , Walker L , Murthy RK 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Paplomata E, Borges V, Loi S, Abramson V, Hamilton E, Hurvitz S, Lin N, Walker L, Murthy 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 OT2-07-08.
Abstract P1-05-03: Isoform specific targeting of insulin receptor
Authors: LaPara K , Chan JY , Zdechlik A , Ljunggren K , Schmidt D , Hackel B , Yee D 
Published: May 2019

Abstract
The insulin receptor (InsR) exists in both an A and B isoform. InsR-B differs from InsR-A by the inclusion of exon 11, which encodes 12 amino acid residues at the C-terminus of the InsR alpha-subunit. Increased InsR-A expression is associated with mitogenic signaling pathways while InsR-B is linked to insulin-mediated metabolic functions. Predominant InsR-A expression may therefore be important in growth and fetal development of embryos, whereas predominant InsR-B expression has a role in metabolic insulin action in adult life. Increased InsR-A expression is seen in breast cancer. In endocrine resistant breast cancer, InsR-A is expressed at high levels (Gradishar, et al. Clin Cancer Res 22:301 2016 PMID: 26324738). Thus, developing InsR-A specific inhibitors could be a useful therapy for breast cancer. We have previously published InsR specific binders using a T7 phage gene 2 protein (Gp2), a small protein scaffold (Chan, et al. Mol Cancer Ther 16:1324 2017 PMID: 28468775), with the long-term goal of creating effective InsR inhibitors and diagnostics. Using yeast display and directed evolution, we identified three Gp2 variants (Gp2 #1, #5, and #10) with low nanomolar affinity and specific binding to cell surface InsR. We have shown that these Gp2 variants inhibited insulin-mediated monolayer proliferation in both endocrine-sensitive and resistant breast cancer, but did not downregulate InsR expression. To further characterize the specificity of Gp2 variants, we used two techniques. HEK293T cells were infected with lentiviral vectors expressing either InsR-A tagged with mCherry or InsR-B tagged with eGFP. Using these cells, we performed “mock panning” and showed the Gp2 #5 variant bound both InsR-A and InsR-B, but had higher affinity for InsR-B. We also incorporated Gp2 #5 into the capsid of a tropism-null adeno-associated virus (AAV). Using this Gp2-AAV, we infected HEK293T-InsR-A or InsR-B cells at a number of different multiplicities of infection. These data were consistent with panning data and showed specific Gp2-AAV infection of cells expressing high levels of InsR-B, but not InsR-A. Thus, our data show that Gp2 variants we created have a higher affinity for InsR-B than InsR-A. Despite this preferred affinity, these Gp2 binders have sufficient binding to InsR-A to disrupt the biological effects of insulin in breast cancer cells. Thus, even relatively low affinity binding to InsR-A can disrupt its function. Further development of InsR-A Gp2 binders may be developed and provide more specific targeting of the breast cancer specific isoform of InsR.
Citation Format: LaPara K, Chan JY, Zdechlik A, Ljunggren K, Schmidt D, Hackel B, Yee D. Isoform specific targeting of insulin receptor [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 P1-05-03.
Abstract P1-05-06: Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with breast cancer
Authors: Gunaldi M , Isiksacan N , Pehlivan S , Binboga S 
Published: May 2019

Abstract
Background: Endothelial nitric oxide synthase (eNOS), also known as NOS3 is an enzyme that in humans is encoded by the NOS3 gene located in the 7q35-7q36 region of chromosome 7. Nitric oxide (NO) is synthesized from L-arginine by eNOS in the vascular endothelium and plays crucial roles in cellular proliferation. In the present study, it is hypothesized that polymorphisms of the Intron4b/a variable number of tandem repeat (VNTR) polymorphism Intron4b/a in the eNOS gene may be associated with an increased risk in the developing breast cancer.
Methods: We included 38 (38 F/Female) patients with breast cancer and 70 (44M/26F) healthy controls. The VNTR polymorphism in intron4 (intron4b/a) was analyzed by PCR. The results were statistically analyzed by calculating the odds ratios (OR) and 95% confidence intervals using the χ2 test.
Results: The distributions of genotype and allele frequency was compared among the groups. The bb, ab and aa genotypes were observed in 29 [76.3%], 9 [23.7%], 0 [0%] patients with breast cancer and in 33 [47.1%], 15 [21.4%], 22[31.5%] healthy controls respectively. The b and a alleles were observed in 67 [88.2%], 9 [11.8%] patients with breast cancer and in 81 [57.8%], 59 [42.2%] healthy controls respectively. The susceptibility to patients with breast cancer had significantly higher frequencies in bb genotype (p=0.004 OR=3.613). The patients with breastcancer had significantly lower frequencies in aa genotype (p=0.001,OR=1.458). The frequency of the a allele was significantly lower in the patients with breast cancer (p=0.001, OR=4.070).
Comparison of eNOS / VNTR polymorphism between patients with Breast and healthy control subjects.eNOS VNTRBreastHealthy ControlsOR*%95 CI*pGenotypesn=38 (%)n=70 (%) BB29 (76.3)33 (47.1)3.613 a1.494-8.735 a0.004 a 3.065 b1.440-6.520 b0.004 bAB9 (23.7)15 (21.4)0.879 a0.343-2.252 a0.812 a 0.9020.388-2.096 b0.832 bAA0 (0)22 (31.5)1.458 a1.244-1.709 a0.001 a 12.375 b2.764-55.396 b0.001 bAllele B67 (88.2)81 (57.8)5.422 a2.505-11.740 a0.001 aA9 (11.8)59 (42.2)4.070 b2.199-7.533 b0.001 b* Fisher's Exact Test a, comparison of genotype and allele frequencies between breast and healthy control groups
Conclusion: We conclude that there was sensible correlation between eNOS gene intron 4b/a VNTR polymorphism and the risk of breast cancer and bb genotype frequency was significantly higher in these patients than healthy controls.
Citation Format: Gunaldi M, Isiksacan N, Pehlivan S, Binboga S. Endothelial nitric oxide synthase gene intron4 VNTR polymorphism 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 P1-05-06.
Abstract P1-06-10: Combined tandem affinity purification mass-spectrometry technique with genome-editing CRISPR-Cas9 knockout screening to identify potential subunits in the BRCA1 complex
Authors: Zhao H , Jiang H , Sun W , Shao Z , Hu X 
Published: May 2019

Abstract
Background: Genomic instability is one of tumor characteristics. Enhancing the DNA damage load or impairing the ability of DNA damage repair has been therapeutics of cancer. Breast cancer type 1 susceptibility gene (BRCA1) has been studied a lot about the DNA damage and repair in breast cancer and ovarian cancer. BRCA1 mutation increases the risk of developing breast cancer by an eighth to tenth. The C terminal domain of BRCA1 can associates with three proteins Abraxas, Bach1 and CtIP in a phosphorylation-dependent manner forming mutually exclusive complexes, namely BRCA1-A, B, and C complexes. The BRCA1-A complex is necessary in DNA damage repair, and study implicates the complex play roles in chemotherapy resistance.
Methods: We explored tandem affinity purification mass-spectrometry (TAP-MAS) technique to identify potential subunits associated with NBA1(one component of BRCA1-A complex). Then we made the genome-editing CRISPR-Cas9 sgRNA library into lentivirus to infect U2OS cells. And 5 Gy dose of Ionizing radiation (IR) was used to induce DNA damage on the cell. After 14 days cultivation, we extracted the DNA from the cells, performed polymerase chain reaction (PCR) and analyzed the correlation between potential genes and DNA damage-repair passage by bioinformatics methods. We generated 200 breast cancer patient tissue samples in our cancer center and performed immunostaining assay.
Results: By the TAP-MAS technique of NBA1 tagged with HA and Flag, we found 93 potential subunits except those known subunits in BRCA1-A complex. Combined with CRISPR-Cas9 sgRNA library screening, we scored the relativity of DNA damage and repair passageway of identified 93 potential subunits. We found that nucleoside-triphosphatase, cancer-related (NTPCR) as a new potential subunit of BRCA1-A complex (P value=0.0034) had the highest score. Endogenous and exogenous co-IP validated NTPCR physically associates with subunits within BRCA1-A complex. Besides, we found that NTPCR associated with the same domain of NBA1 as the other subunits in BRCA1-A complex. Immunohistochemistry of patient tissue samples indicated that high levels of NTPCR expression was correlated with poor prognosis in multivariate analysis (HR: 4.990; 95%CI: 1.433-17.378; p value: 0.012).
Conclusion: NTPCR is a new subunit in BRCA1-A complex. And high expression of NTPCR is a negative prognostic factor in breast cancer patients.
Citation Format: Zhao H, Jiang H, Sun W, Shao Z, Hu X. Combined tandem affinity purification mass-spectrometry technique with genome-editing CRISPR-Cas9 knockout screening to identify potential subunits in the BRCA1 complex [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 P1-06-10.
Abstract P1-11-05: Withdrawn
Authors: Bundred NJ , Foden P , Riches K , Morris J , Evans A , Todd C , Bramley M , Skene A , Watterson D , Purushotham A , Keeley V 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Bundred NJ, Foden P, Riches K, Morris J, Evans A, Todd C, Bramley M, Skene A, Watterson D, Purushotham A, Keeley V. 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 P1-11-05.
Abstract P1-11-13: Depomedroxyprogesterone therapy for hot flashes in survivors of ER-expressing breast cancer: Impact on recurrence and survival
Authors: Ertz-Archambault N , Rogoff L , Kosiorek H , Ernst B , Anderson K , Pockaj B , Gray R , Northfelt D 
Published: May 2019

Abstract
Background
Survivors of ER-expressing operable breast cancer (ER+BC) generally do not receive hormone replacement therapy for menopausal symptoms due to concern about provoking recurrence of disease. Single dose depomedroxyprogesterone acetate (MPA) 400 mg IM has previously been shown (Loprinzi CL, et al. J Clin Oncol 2006;24:1409) to be the most effective non-estrogen therapy available for menopausal hot flashes (HF) but long-term evidence of safety in survivors of ER+BC is lacking.
Methods
Consecutive patients previously diagnosed with ER+BC who received MPA for HF between January 2007 and December 2012 were retrospectively identified in the breast cancer patient database at Mayo Clinic Arizona. Medical records were audited for breast cancer outcomes in these cases and in contemporaneous control patients with ER+BC who did not receive MPA, matched for age, stage of disease, and year of diagnosis. Statistical comparisons of local-regional recurrence and event-free survival were performed.
Results
92 patients who received MPA were identified and matched 1:1 with contemporaneous controls. Median follow-up duration was 5.7 years in cases and 4.5 years in controls. Estimated local-regional recurrence free survival at 10 years was 85% (95% CI, 72-100%) in cases and 95% (95% CI, 86-100%) in controls. Matched pairs hazard ratio was 1.0 (95% CI, 0.06-16.0) for local-regional recurrence free survival. Estimated event-free survival at 10 years was 81% (95% CI, 69-97%) in cases and 76% (95% CI, 64-92%) in controls. Matched pairs hazard ratio was 0.38 (95% CI, 0.10-1.41) for event-free survival. The majority (77%) of case patients experienced satisfactory relief of hot flashes from MPA injection.
Conclusion
In this retrospective case-control study we were unable to identify a detrimental effect of MPA therapy for HF in survivors of ER+BC. MPA may be acceptable for management of HF in this population.
Citation Format: Ertz-Archambault N, Rogoff L, Kosiorek H, Ernst B, Anderson K, Pockaj B, Gray R, Northfelt D. Depomedroxyprogesterone therapy for hot flashes in survivors of ER-expressing breast cancer: Impact on recurrence and survival [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 P1-11-13.
Abstract P1-16-07: Progression-free survival is a surrogate of survival in maintenance therapy for metastatic breast cancer: Randomized trial level analysis
Authors: Song E , Yao H , Yu Y , Ou Q , Wang Y 
Published: May 2019

Abstract
Background:The validity of progression-free survival (PFS) as a surrogate end point for overall survival (OS) in maintenance therapy trials of metastatic breast cancer (MBC) is uncertain. We aimed to compare treatment effect sizes and the strength of associations between OS and PFS in trials of maintenance therapy for MBC.
Methods: We searched for randomized trials investigating maintenance chemotherapy, endocrine therapy or immunotherapy after first-line chemotherapy in MBC and selected those reporting results for both OS and PFS. Treatment effect size differences between OS and PFS by a ratio of hazard ratios (rHRs) with 95% confidence intervals [CIs] were evaluated using random effects analysis. Surrogacy were analyzed using a weighted linear regression model, correlations were evaluated by squared correlation R2.
Results: We analyzed data from 16 trials and 3,898 patients that received maintenance chemotherapy, endocrine therapy or immunotherapy for MBC. In the all trial-level analysis, treatment effect sizes were 28% greater for PFS than for OS (combined rHR, 0.72; 95% CI, 0.62 to 0.85, P &lt; 0.001), and the correlation coefficient R2 between PFS and OS was 18% (95% CI, 12% to 26%). Differences were greater with PFS than OS for trials of maintenance chemotherapy compared with observation (rHR, 0.72; 95% CI, 0.59 to 0.80, P &lt; 0.001), and the correlation coefficient R2between treatment effects on PFS and on OS ranged from 12% (95% CI, 8% to 16%) when all trials were considered to 40% (95%CI, 30% to 54%) after exclusion of one highly influential trial by sensitivity analysis. Differences were also great for trials of maintenance endocrine therapy vs. observation (rHR, 0.54; 95% CI, 0.44 to 0.66), and immunotherapy vs. observation (rHR, 0.85; 95% CI, 0.80 to 0.91).
Conclusion: PFS was greater than OS in the treatment effect sizes, which is a valid surrogate end point for OS to assess treatment effect in MBC maintenance therapy trials.
PROSPERO registry: No. CRD42017071858; Support: ChiCTR-IIR-17014036, SYS-C-201801.
Citation Format: Song E, Yao H, Yu Y, Ou Q, Wang Y. Progression-free survival is a surrogate of survival in maintenance therapy for metastatic breast cancer: Randomized trial level analysis [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 P1-16-07.
Abstract P1-20-06: Association of circulating tumor DNA with clinical outcomes in metastatic breast cancer patients
Authors: Tan AR , Symanowski J , Kim EN , Hosking M , Morris CD , Plagnol V , Farhangfar CJ , Ersek JL 
Published: May 2019

Abstract
Background: Circulating tumor DNA (ctDNA) can be used as a non-invasive method to detect and quantify genomic alterations (GA) in blood. We evaluated the relationship between ctDNA features, radiographic disease progression (RDP) and progression-free survival (PFS) in patients (pts) with metastatic breast cancer (MBC).
Methods: A retrospective analysis of 32 female MBC pts with plasma ctDNA tested prior to a radiology scan was performed. Plasma ctDNA tests were run by Inivata using a 36-gene panel for detecting point mutations, short insertions/deletions, and copy number variations. ctDNA features were tabulated for each pt and included number of genomic alterations (numGA), maximum mutant allele frequency (maxMAF), and sum of mutant allele frequency (sumMAF). Univariate and multivariable logistic regression (LR) models were used to explore ctDNA features associated with RDP. Univariate and multivariable Cox proportional hazards models were used to identify ctDNA features that were associated with PFS. All models included ctDNA features as continuous variables.
Results: Frequency of subtypes were 38% HR+HER2-, 28% HR+HER2+, 28% triple-negative, and 6% HR-HER2+. 97% had prior chemotherapy; 92% of HR+HER2-negative pts had prior endocrine therapy. 20 of 32 samples (69%) had GAs. The most common GAs were TP53 (50%), ESR1 (25%), PIK3CA (19%), and GATA3 (9.4%). Median numGA was 1 (0-12); median maxMAF was 1.9 (0-65.5); median sumMAF was 2.2 (0-157.2). Univariate LR analysis identified numGA (p=0.025), maxMAF (p=0.034), and sumMAF (p=0.049) to be significantly associated with RDP; numGA (p=0.056) and maxMAF (p=0.109) were retained in the final multivariable LR model. Univariate Cox regression analysis showed that numGA (HR=1.32, p&lt;0.001), maxMAF (HR=1.03, p=0.011), and sumMAF (HR=1.02, p=0.002) were significantly associated with PFS; numGA (HR= 1.30, p=0.001) and maxMAF (HR= 1.02, p=0.045) were retained in the final multivariable Cox model.
Conclusions: Blood ctDNA profiling contributes to the prediction of RDP and PFS in MBC pts. High number of alterations and high allele fraction of these alterations were associated with worse clinical outcomes. These data provide an overview of the ctDNA dynamics in treated MBC pts.
Citation Format: Tan AR, Symanowski J, Kim EN, Hosking M, Morris CD, Plagnol V, Farhangfar CJ, Ersek JL. Association of circulating tumor DNA with clinical outcomes in 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 P1-20-06.
Abstract P2-01-20: LAP2alpha, a novel tumor marker candidate is related to metastasis of breast cancer
Authors: Hu Y , Qiu J , Zhou M , Li X , Huang Y 
Published: May 2019

Abstract
Background: To date, there is no suitable serum marker for diagnosis and prognosis of breast cancer. In our early research, a new tumor marker candidate of breast cancer whose molecular weight was 5.6 kDa was screened from serum using mass spectrometry technology. It was decoded to be a fragment of isoform alpha of lamina-associated polypeptide 2 (LAP2α). The survival analysis revealed that LAP2α was over-expressed in breast cancer patients and indicated poor prognosis.
Materials and Methods: Immunohistochemistry (IHC) was utilized to evaluate LAP2α expression in paired primary breast tumor, metastasis of axillary lymph node and ipsilateral normal breast tissue of 29 breast cancer patients. An inhibition plasmid vector of LAP2α-small hairpin RNA (LAP2α-shRNA) was constructed and transfected into MCF-7 cells. The abilities of cell proliferation and metastasis were assessed both in vitro and in vivo. The association of LAP2α with epithelial-to-mesenchymal transition (EMT) was determined by western blot.
Results: LAP2α expression of paired tissue descended in order of metastasis of axillary lymph node (21/29, 72.4%), primary breast tumor (11/29, 37.9%) and ipsilateral normal breast tissue (4/29, 13.8%) (P&lt;0.05 in comparisons between each two groups). CCK-8 experiments on transfected and control cells showed that inhibition of LAP2α could not influence cell proliferation. Transwell and matrigel-transwell assays indicated that inhibition of LAP2α could significantly reduce cell migration and invasion abilities. In vivo experiments utilizing subcutaneous xenograft model and tail vein-injection mouse model revealed that the down-regulation of LAP2α might suppress tumorigenesis and metastasis of breast cancer. Western blot suggested that down regulation of LAP2α increased the E-cadherin expression level but repressed N-cadherin and vimentin expression levels.
Conclusions: A novel tumor marker candidate, LAP2α is related to metastasis of breast cancer both in clinical samples and tissue culture experiments. Inhibition of LAP2α could suppress aggressiveness and metastasis of breast cancer probably via EMT suppression.
Funding: The Natural Science Foundation of Zhejiang Province of China (No. LY14H160030 and LY13H160011), the National Program on Key Basic Research Project of China (973 Program; No. 2014CB542003), the National Natural Science Foundation of China (No. 30801341) and Zheng Shu Elite Scholarship for Clinical Medicine.
Citation Format: Hu Y, Qiu J, Zhou M, Li X, Huang Y. LAP2alpha, a novel tumor marker candidate is related to metastasis of 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 P2-01-20.