bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-02-06: Evaluation of contrast-enhanced ultrasonography for early prediction of response to neoadjuvant chemotherapy in triple negative breast cancer
Authors: Masumoto N , Kadoya T , Murakami C , Gouda N , Sasada S , Emi A , Haruta R , Kataoka T , Okada M 
Published: March 2017

Abstract
Objectives
We aimed to determine whether contrast-enhanced ultrasonography (CEUS) can predict the early effects of neoadjuvant chemotherapy on triple negative breast cancer.
Methods
The clinical responses of 20 consecutive patients with breast cancer (T1–2, N0–1, M0) to neoadjuvant chemotherapy between October 2012 and Feb 2016 were assessed using ultrasonography and contrast-enhanced ultrasonography before starting the therapy and after the treatment of 2 courses. Ascending slope (AS) of perfusion parameters for contrast-enhanced ultrasonography were created from time–intensity curves based on enhancement intensity and temporal changes to objectively evaluate contrast-enhanced ultrasonography findings.We investigated whether rate of change of ascending slope (ΔAS) and tumor size (Δ US) could predict pCR.
Results
Eight (40.0%) of the 20 patients achieved pathological complete response. ΔAS were significantly higher (-25.5 ± 35.5 vs. 14.7 ± 33.2; P &lt; 0.02) in patients who achieved pCR than in those who did not. On the other hand, ΔUS of pCR and non-pCR did not significantly differ among tumors (-40.8 ± 22.4 vs. -21.4 ± 20.6; P = 0.06). The AUC values for ΔAS and ΔUS were 0.792 (95% CI, 0.579 -1.000, P = 0.03) and 0.729 (95% CI, 0.501 - 0.957;p = 0.09), respectively. We set ΔAS and Δ US cut-offs for predicting pCR at-20.08 and - 33.75 based on the ROC curves. Clinical and pathological characteristics of the 20 patients are summarized in Univariate (odds ratio, 2.71; p= 0.02) and multivariate (odds ratio, 2.88; p= 0.03) analysis showed that ΔAS was the sole independent predictor of pCR.
Clinical and pathological characteristics of patients with breast cancer.CharacteristicpCR (n)Non pCR (n)pClinical T status T1110.71T2711 Clinical N status Negative570.85Positive35 Nuclear Grade 1 or 2340.85358 ΔUS (%) &lt; -33.75390.09≥ -33.7553 ΔAS (%) &lt; -20.082100.009≥ -20.0862
Univariate and multivariate logistic analysis of significant predictive factors for pCR in triple negative subtype Univariate analysisMultivariate analysis OR, 95% CI, pOR, 95% CI, pΔUS &gt; -33.751.61, 0.72-34.7, 0.101.85, 0.51-79.1, 0.15≤-33.75 ΔAS &gt; -20.082.71, 1.65-136.1, 0.022.88, 1.44-218.7, 0.03≤ -20.08
Conclusion
ΔAS assessed with CEUS can help the physician to early predict the probability of achieving pCR or not.
Citation Format: Masumoto N, Kadoya T, Murakami C, Gouda N, Sasada S, Emi A, Haruta R, Kataoka T, Okada M. Evaluation of contrast-enhanced ultrasonography for early prediction of response to neoadjuvant chemotherapy 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 P4-02-06.
Abstract P4-02-08: Opto-acoustic imaging of the breast: Downclassification and upclassification of suspicious breast masses
Authors: Menezes GLG , Pijnappel RM , Meeuwis C , Bisschops B , Veltman J , Lavin PT , Mann RM 
Published: March 2017

Abstract
Background
Imagio® is an opto-acoustic (OA) breast imaging system designed to concomitantly collect OA images together with diagnostic ultrasound (CDU). The device is intended to improve distinction between benign and malignant masses. In this interim analysis of the post-market surveillance MAESTRO study we report the results of 75 patients who had breast masses classified as BI-RADS 4a and 4b by CDU.
Aim
We assessed OA's sensitivity, specificity, and its ability to downgrade benign masses and upgrade malignant masses based on the probability of malignancy (POM) and BI-RADS category.
Methods
Seventy-five patients with 78 breast masses were evaluated with OA prior to biopsy. For each mass, the radiologist scored 5 OA features, assigned a POM and BI-RADS category. OA sensitivity, specificity, and BI-RADS downgrade and upgrade percentages were assessed with and without contribution from a previously derived nomogram.
Results
The mean POM difference between malignant and benign masses was higher for OA (37%) than for CDU (27%). OA specificity was 43% without the nomogram and 68% with the nomogram. OA sensitivity was 97% with and without the nomogram. With OA 43% of benign masses could be downgraded and 47% of malignant masses could be upgraded in BIRADS category.
Conclusion
These results appear to confirm the previously reported ability of OA to improve the differentiation between benign and malignant masses compared to CDU alone, to potentially decrease negative biopsies, and to upgrade BI-RADS category in malignant masses. The MAESTRO study (n=200) may further confirm these results.
Citation Format: Menezes GLG, Pijnappel RM, Meeuwis C, Bisschops B, Veltman J, Lavin PT, Mann RM. Opto-acoustic imaging of the breast: Downclassification and upclassification of suspicious breast masses [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 P4-02-08.
Abstract P4-02-13: Breast ultrasound surveillance with image fusion technique in a short-interval follow-up for BI-RADS category 3 mass lesions
Authors: Nakano S , Fujii K , Kousaka J , Mouri Y , Ando T 
Published: March 2017

Abstract
PURPOSE: Breast ultrasound (US) is a diagnostic imaging modality that is now widely used as an adjunct to mammography for evaluation of breast abnormalities. In the Breast Imaging-Reporting and Data System (BI-RADS) lexicon, a solid mass with an oval shape, well-circumscribed margins and parallel orientation is classified as category 3 (BI-RADS category 3 mass lesions) . This mass should have a risk of malignancy of &lt; 2%. Surveillance breast US in short-interval follow-up for BI-RADS category 3 mass lesions is an acceptable alternative to biopsy. The surveillance US is recommended 6 month after initial lesion identification and then every year for at least 2 y. However, inconsistent reproducibility for US due to operator dependence is still a clinical issue. The aim of our study was to verify the utility of US using real-time virtual sonography (RVS) - to coordinate present US images with past US images reconstructed from previously acquired US volume data using magnetic tracking system – in a short-interval follow--up for BI-RADS category 3 mass lesions.
METHOD AND MATERIALS: We enrolled 20 women (23 lesions) with more than 24 months of follow-up after classification as BI-RADS category 3 during initial US. US surveillance was scheduled at 6, 12 and 24 months. Three-dimensional assessment of morphologic features was performed while serially checking past US volume data corresponding to the present US probe position. Measurement of the target lesion diameter was performed after the probe was adjusted to include the maximum diameter of a past US image at each visit.
RESULTS: RVS was technically successful in 100% of patients. All target lesions were detected, including two iso-echoic lesions. The mean target lesion diameters at baseline and at 6, 12 and 24 months were 8.2+4.2, 8.4+4.5, 8.1+4.5 and 8.3+5.0 mm, respectively . Statistical analysis using a Friedman test with multiple comparisons revealed no significant difference between the diameters at each time point (p = 0.785). RVS was used to directly compare the US morphologic characteristics and sized of lesions. Furthermore, the RVS data can be reproduced in their entirety for independent review at a later date by using stored US volume data.
CONCLUSION:Our results suggest that RVS is reproducible, operator-independent technique for comparison of US images of BI-RADS category 3 mass lesions obtained at different time points.
Citation Format: Nakano S, Fujii K, Kousaka J, Mouri Y, Ando T. Breast ultrasound surveillance with image fusion technique in a short-interval follow-up for BI-RADS category 3 mass lesions [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 P4-02-13.
Abstract P4-03-06: Microenvironmental control of breast cancer subtype elicited by paracrine growth factors signaling
Authors: Bocci M , Bartoschek M , Pietras K 
Published: March 2017

Abstract
During cancer progression from an indolent stage to a clinically manifested disease, the surrounding microenvironment co-evolves into an activated state through continuous and dynamic paracrine communication between all constituent cell types that collectively sustain malignant growth. Hence, from a therapeutic perspective, tumors must be regarded as multi-cellular organs. Mesenchymal cells are highly plastic entities. Normal fibroblasts are described to counteract tumorigenesis by repressing cancer initiation. However, co-evolution of the malignant epithelium and its underlying stroma instigates activation of cancer-associated fibroblasts (CAFs) into a phenotype endorsing most, if not all, hallmarks of cancer progression.
Through translational studies using breast cancer patient cohorts, genetically engineered mouse models (including patient derived xenografts), and single-cell RNA sequencing, we delineate a previously unappreciated role for CAFs as determinants of breast cancer prognosis and treatment response through specification of the molecular subtype of breast cancer.
Expression of paracrine growth factors mediating malignant cell-CAF crosstalk in breast cancer was found to be associated with a hormone receptor-negative state. Genetic targeting of the signaling networks governing the interactions between tumor cells and CAFs confirmed their functional importance by prompting a delay in tumor growth, impaired extra-cellular matrix deposition and reduced angiogenesis. Importantly, our work holds therapeutic implications, as genetic or therapeutic targeting of CAF subsets resulted in conversion of basal-like/triple-negative breast tumors into a luminal state that conferred sensitivity to endocrine therapy in previously impervious tumors. Additionally, to mechanistically explore the heterogeneity of mesenchymal cells in breast tumors, we have made use of single cell RNA sequencing of isolated CAFs as a guide to divide cells into transcriptionally similar groups. Distinct clusters of different CAF subtypes were identified and found to denote diverse functions in the tumor microenvironment.
In conclusion, therapeutic targeting of functional subsets of CAFs may be exploited as a refined strategy to improve patient benefit from established treatments by impinging on the stimulatory crosstalk between CAFs and their surrounding malignant microenvironment.
Citation Format: Bocci M, Bartoschek M, Pietras K. Microenvironmental control of breast cancer subtype elicited by paracrine growth factors signaling [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 P4-03-06.
Abstract P4-06-04: Triple negative breast cancer patient-derived xenografts: Molecular characteristics and sensitivity to emerging therapies
Authors: Evans KW , Yuca E , Akcakanat A , Scott SM , Paez Arango N , Zheng X , Chen K , Tapia C , Tarco E , Eterovic AK , Black DM , Jennifer LK , Tripathy D , Mills GB , Meric-Bernstam F 
Published: March 2017

Abstract
Background: Patients with triple negative breast cancer (TNBC) that have significant residual disease following neoadjuvant therapy have a poorer prognosis. The difficulty in developing improved treatment strategies for these patients is compounded by the molecular diversity of this pathology. Thus, preclinical efficacy testing with models representing the molecular heterogeneity of TNBC may not only improve efficacy testing but also has the potential to facilitate biomarker discovery to inform patient selection.
Methods: We generated 28 hormone receptor-low/HER2- patient-derived xenografts (PDXs) from 26 patients; the majority from residual disease following neoadjuvant chemotherapy. We characterized the tumors from the patients and the matched PDXs by targeted exome sequencing, RNA sequencing, and Reverse Phase Protein Arrays. We established single agent sensitivity for a set of PDXs to standard TNBC therapies as well as emerging targeted therapies targeting PARP, mTOR, PI3K and MEK1/2.
Results: PDXs maintained DNA/RNA profiles similar to the patients' tumors. Our PDX set exhibits a diverse set of potential driver alterations and is comprised of PDXs representative of all TNBC molecular subtypes. The PDXs varied in their sensitivity to standard chemotherapeutics. PI3K, mTOR and MEK inhibition caused tumor growth inhibition in several PDX models but were unable to cause tumor regression as single agent. In contrast, talazoparib caused dramatic regression in 5 out of 12 PDXs tested, including 3 PDXs from patients whose tumors had progressed on neoadjuvant anthracyclines and/or paclitaxel. Four of these talazoparib sensitive PDXs were derived from patients not harboring BRCA1/2 germline alterations; three had somatic alterations in genes linked to DNA damage repair (ATM, BRCA2, PTEN). The comparison of PARP sensitivity with molecular profiles will be presented.
Conclusions: TNBC PDXs represent molecular tumor heterogeneity as well as heterogeneity in response to targeted therapeutics. PDXs represent an opportunity for biomarker discovery as well as for rationale combination therapies to enhance the efficacy targeted therapies.
Citation Format: Evans KW, Yuca E, Akcakanat A, Scott SM, Paez Arango N, Zheng X, Chen K, Tapia C, Tarco E, Eterovic AK, Black DM, Jennifer LK, Tripathy D, Mills GB, Meric-Bernstam F. Triple negative breast cancer patient-derived xenografts: Molecular characteristics and sensitivity to emerging therapies [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 P4-06-04.
Abstract P4-07-06: MicroRNAs associated with acquired taxane resistance in a breast cancer cell line model
Authors: Taylor KJ , Chong T , D'Costa A , Yao C , Gourley C , Cameron DA , Bartlett JMS , Spears M 
Published: March 2017

Abstract
Background: Acquired chemoresistance remains the major cause of therapeutic failure in the treatment of breast cancer. Improved knowledge of the transition from drug sensitive to resistant breast cancer will pave the way for novel preventative and therapeutic strategies. MicroRNAs (miRNA) are endogenous, small non-coding RNAs that regulate gene expression by targeting the 3'UTR region of messenger RNAs. There is a growing body of evidence to suggest miRNAs may be involved in the development of chemoresistance and may play a role in the regulation of drug resistance pathways.
Methods: An in vitro model of paclitaxel resistance was developed through the generation of resistant MDA-MB-231 cell lines by serial culture in escalating doses of taxane until resistance was achieved. The chemoresistant model was used to compare differential miRNA expression with the sensitive, parental line using the Nanostring® platform, analysing 800 human miRNAs. Confirmation of differential expression was performed by QRT-PCR.
Results: This analysis resulted in 30 significantly altered miRNA (1.5 fold, p value &lt; 0.05) at 25nM paclitaxel and 48 significantly altered miRNA at 50nM paclitaxel. The top up-regulated miRNA cluster in MDA-MB-231 25PACR is hsa-miR-548l (fold change: 2.89, p value: 0.016) and top down-regulated was hsa-miR-449a (fold change: -4.1. p value: 0.001). In MDA-MB-231 50PACR the top up-regulated miRNA cluster is hsa-miR-193a-5p (fold change: 3.746, p value: 0.008) and the top down-regulated miRNA cluster is hsa-miR-135a (fold change: -4.085, p value: 0.001). To explore the molecular mechanisms of the differentially expressed miRNAs in paclitaxel resistance, targets were predicted by in silico analysis. Pathways and networks designated by miRNA targets included the cell cycle, PI3K/Akt pathways and focal adhesion.
Conclusion: In this study we identified candidate resistance-associated miRNAs which were differentially expressed between in vitro derived paclitaxel resistant MDA-MB-231 and the sensitive parental line. Further validation to ascertain their role in the transition to a chemoresistant phenotype is currently ongoing.
Citation Format: Taylor KJ, Chong T, D'Costa A, Yao C, Gourley C, Cameron DA, Bartlett JMS, Spears M. MicroRNAs associated with acquired taxane resistance in a breast cancer cell line model [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 P4-07-06.
Abstract P4-11-01: A genetic model of mammary gland fibrosis and cancer risk
Authors: Wu J , Crowe D 
Published: March 2017

Abstract
Ductal cells of the mammary gland arise from mammary stem cells (MSC) and consist of estrogen receptor a negative (ER-) luminal cells and a small ER+ luminal population. Luminal cells are maintained by the proliferation of ER- luminal progenitor (LP) cells, which are expanded in basal subtype breast cancer. Human breast LP cells exhibit telomere DNA damage, which is associated with mammographic density and increased cancer risk. Short telomeres resulting from the DNA damage response correlate with aggressive breast cancer phenotypes. Telomeric repeat factor 2 (TRF2) binds to telomeres and protects them from the DNA damage response. TRF2 expression is reduced in most human breast cancers but the phenotypic advantages of this genetic alteration are unknown. To determine the effects of telomere DNA damage on mammary gland function and tumor phenotype, we deleted TRF2 expression in mammary gland epithelium. Mammary glands lacking TRF2 expression exhibited increased telomere DNA damage response, histopathological and functional degeneration, and prominent ductal fibrosis. MSC from TRF2 deficient glands were unable to completely regenerate mammary glands following transplantation to cleared fat pads. TRF2 deficient mammary tumors also demonstrated telomere DNA damage response but exhibited rapid onset and increased proliferation. Tumor derived LP cells underwent expansion but exhibited high telomere DNA response and failed to form tumors following transplantation. In contrast, the severely depleted MSC population was highly tumorigenic and maintained telomeres via the ALT mechanism. Telomere DNA damage response in mammary tumors resulted in p53 dependent ER+ cellular differentiation and sensitivity to anti-estrogen therapy. Our results provide a new in vivo model for exploring mechanisms of mammographic density, stem cell differentiation, cancer risk, and therapeutic sensitivity.
Citation Format: Wu J, Crowe D. A genetic model of mammary gland fibrosis and cancer risk [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 P4-11-01.
Abstract P4-12-03: Estrogen receptor-positive breast cancer in BRCA1 mutation carriers shows a BRCAness profile, suggesting sensitivity to drugs targeting homologous recombination deficiency
Authors: Lips EH , Debipersad R , Scheerman E , Mulder L , Sonke GS , van der Kolk LE , Wessling J , Hogervorst FBL , Nederlof PM 
Published: March 2017

Abstract
Background
As estrogen receptor (ER)-positive breast cancer in BRCA1 mutation carriers arises at an older age with less aggressive tumor characteristics than ER negative BRCA1 mutated breast cancer, it has been suggested that these tumors are 'sporadic' and not BRCA1-driven. With the introduction of targeted treatments specific for tumors with a non-functioning BRCA1 or BRCA2 gene, the question whether the BRCA genes are impaired in the tumor, is highly relevant. Therefore, we performed genomic profiling of BRCA1-mutated ER+ tumors.
Methods
Genomic profiling, BRCA1 promoter methylation assessment, and loss of heterozygosity (LOH) analysis were done on 16 BRCA1-mutated ER+ tumors. Results were compared with 57 BRCA1-mutated ER- tumors, 36 BRCA2-mutated ER+ associated tumors, and 182 sporadic ER+ tumors.
Results
The genomic profile of BRCA1-mutated ER+ tumors was different from BRCA1-mutated ER- breast tumors, but highly similar to BRCA2-mutated ER+ tumors. In 83% of the BRCA1-mutated ER+ tumors, loss of the wildtype BRCA1 allele was observed. Clinico-pathological variables in BRCA1-mutated ER+ cancer were more similar to BRCA2-mutated ER+ and sporadic ER+ breast cancer than to BRCA1 mutated ER- cancers.
Conclusions
As BRCA1-mutated ER+ tumors showed a BRCAness copy number profile and LOH, it is likely that the loss of a functional BRCA1 protein plays a role in tumorigenesis in BRCA1-mutated ER+ tumors. Therefore, we hypothesize that these tumors are sensitive to drugs targeting the BRCA1 gene defect.
Citation Format: Lips EH, Debipersad R, Scheerman E, Mulder L, Sonke GS, van der Kolk LE, Wessling J, Hogervorst FBL, Nederlof PM. Estrogen receptor-positive breast cancer in BRCA1 mutation carriers shows a BRCAness profile, suggesting sensitivity to drugs targeting homologous recombination deficiency [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 P4-12-03.
Abstract P4-12-10: Prognostic relevance of caspase 8 polymorphisms for breast cancer
Authors: Wimberger P , Jan Dominik K , Agnes B , Kurt S , Rainer C , Rainer K , Winfried S , Hagen B 
Published: March 2017

Abstract
Background: The minor allele of two caspase 8 polymorphisms, namely CASP8 -652 6N InsDel (rs3834129) and CASP8 Asp302His (rs1045485), were repeatedly associated with reduced breast cancer susceptibility. Contrarily, the presence of the -652 6N Del or the CASP8 302His variant was reported to be an unfavorable prognostic factor in colorectal cancer or neuroblastoma. However, prognostic relevance of these genetic variants for breast cancer is completely unknown and is therefore adressed by the current study.
Methods: Genotyping was performed by pyrosequencing. Caspase 8 mRNA expression was quantified by comparative RT-qPCR.
Results: We observed an allele-dose dependent association between CASP8 -652 6N InsDel and caspase 8 mRNA expression in breast cancer tissue, with homozygous deletion carriers showing lowest relative caspase 8 expression (p=0.0131). Intriguingly, the presence of the -652 6N Del or the 302His variant was shown to be a negative prognostic factor for breast cancer in terms of an allele-dose dependent influence on overall survival (OS, p=0.0018, p=0.0150, respectively). Moreover, both polymorphisms were independent predictors of OS after adjusting for co-variats (p=0.007, p=0.037, respectively). Prognostic relevance of both polymorphisms was independent from ER or Her2/Neu receptor status and a combined analysis of diplotypes revealed an additive influence on OS (p=0.0002).
Conclusion: This is the first report, showing negative and independent prognostic impact of the CASP8 -652 6N Del and the 302His variant for breast cancer. Our data provide rationale to further validate clinical utility of these polymorphisms for breast cancer and to extend this investigation to a broad scope of other malignancies.
Citation Format: Wimberger P, Jan Dominik K, Agnes B, Kurt S, Rainer C, Rainer K, Winfried S, Hagen B. Prognostic relevance of caspase 8 polymorphisms for 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 P4-12-10.