bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-13-07: Radiofrequency ablation (RFA) is a promising treatment option for primary breast cancer: Experience in 386 Japanese breast cancer patients
Authors: Takahashi M , Ito T , Oura S , Nagamine S , Yamamoto N , Yamamichi N , Earashi M , Doihara H , Imoto S , Mitsuyama S , Akazawa K 
Published: May 2016

Abstract
Background. Radiofrequency ablation (RFA) is used for the treatment of various solid tumors. Several small experiences have reported as a primary treatment for breast cancer using RFA. However, the clinical benefits remain uncertain. We retrospectively studied 386 patients and analyzed their RFA-related complications and outcomes.
Methods. A clinical database was constructed from 10 institutions. RFA was performed using an electrical generator connected to a single cooled-tip electrode or multiple electrodes. Adjuvant systemic therapy and whole breast radiation were administered according to the clinicopathological background of each patient. Follow-up periods ranged from 1 to 90 months (mean 45.4 months). RFA-related complications and risk factors for in-breast recurrence after RFA were evaluated. Variables evaluated included patient characteristics, pre- and post-operative imaging modalities, tissue sampling modalities, and RFA-related factors.
Results. Skin burns were observed in 7 patients (1.8 %) and RFA-induced damage to the nipple-areolar complex in 7 patients (1.8 %). Persistent induration of the breast after RFA was observed in 137 patients (35.5 %). Eleven patients (2.8 %) developed in-breast recurrence. In-breast recurrence was more frequent in patients with tumor size &gt;2.0 cm, ER-negative tumor, HER2-positive tumor, positive nodes, no breast irradiation and adjuvant chemotherapy.
Conclusions. Skin burns were a major problem after RFA, but the frequency of burns was relatively low. Breast induration was also developed, but it did not bring harmful effect to the patients with this complication. We conclude that RFA is a promising treatment option for solid T1 breast cancer without malignant potential.
Citation Format: Takahashi M, Ito T, Oura S, Nagamine S, Yamamoto N, Yamamichi N, Earashi M, Doihara H, Imoto S, Mitsuyama S, Akazawa K. Radiofrequency ablation (RFA) is a promising treatment option for primary breast cancer: Experience in 386 Japanese breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-13-07.
Abstract P4-02-12: Breast MRI: Enhancing pre-operative planning in women with newly diagnosed breast cancer
Authors: Carr B , Lamb LC , Zarfos K , Weigert J , Singh R 
Published: May 2016

Abstract
Hypothesis:
Preoperative breast MRIs in newly diagnosed breast cancer patients may lead to additional findings, including larger disease involvement, thus leading to a change in the operative plan. This information can led to better surgical planning and decreased rates of surgical re-excisions.
Methods:
This was a single surgeon, single institution, retrospective analysis of women with newly-diagnosed breast cancer who had surgery between December 2013 and December 2014. A total of ninety-six patients underwent preoperative breast MRI. Exclusion criteria were patient's refusal of MRI or surgery, contraindication to MRI based on implants or body habitus, and male patients.
Results:
Overall, breast MRI most closely correlated to pathological tumor size (gold standard). MRI had a 64% correlation with pathology size, whereas mammography and ultrasound correlation were 44% and 43% respectively. As breast density increased, MRI correlation to pathologic tumor size improved. For breast density between 25-50%, tumor size by MRI correlated with pathology size in 27% of patients, mammogram correlation was 33% and ultrasound was 12%. When breast density increased to 51-75%, MRI correlation improved to 92%, whereas mammogram correlation was 56% and ultrasound was 68%. The majority of patients fell within these two density categories; correlation for breast density &lt;25% and &gt;75% were not statistically significant. Of the breast biopsies preformed for MRI abnormalities not otherwise identified by mammography or ultrasound, 42% were positive for invasive cancer or DCIS. Thirty-eight percent of patients had a change in operative plan based on their MRI findings. Of the ninety-six patients, nine were changed from breast conserving surgery to mastectomy, and 29 underwent a larger area of resection than planned prior to MRI, due to findings of more extensive disease on MRI not otherwise appreciated by mammography or ultrasound.
Conclusion:
Pre-operative MRI played a significant role in the pre-surgical evaluation of patients with newly diagnosed breast cancer. In our series, breast MRI demonstrated better correlation with extent of disease compared to other imaging modalities. This is turn enhanced patient and surgeon decision making and led to more precise pre-operative surgical planning.
Citation Format: Carr B, Lamb LC, Zarfos K, Weigert J, Singh R. Breast MRI: Enhancing pre-operative planning in women with newly diagnosed breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-02-12.
Abstract P4-02-14: Incidentally detected enhancing lesions found on preoperative breast MRI: Analysis of T2 signal intensity and apparent diffusion coefficient significantly improve classification
Authors: Arponen O , Sudah M , Masarwah A , Sutela A , Vanninen R 
Published: May 2016

Abstract
Purpose and Background− Reportedly, magnetic resonance imaging (MRI) detects mammographically and sonographically (US) occult incidental lesions in 10-29% of patients with a malignant primary breast lesion. We evaluated diagnostic performance of the BI-RADS reporting system and utility of T2- and diffusion weighted imaging (DWI) for MRI detected additional lesions.
Methods− This prospective study protocol included 3.0T structural breast MRI with T2-weighted imaging and DWI performed according to EUSOMA guidelines in 112 consecutive patients with primary breast lesions (mean age 57.0±12.7 years, range 38-80 years). Breast lesions with one or more suspective feature according to the BI-RADS lexigon were biopsied. T2 signal intensity (SI) and DWI findings were assessed.
Results− Altogether 33 (29.5%) patients had 36 primarily MRI detected incidental additional lesions. In addition, 36 sographically or mammographically detected lesions were histopathologically confirmed and a total of 8 lesions were followed up. Of incidental lesions, 16 (44.4%) proved to be malignant. Mean size was 0.82±0.29 cm (range 0.5 cm to 1.5 cm) and 1.5±1.61 cm (range 0.5 cm to 5.0 cm) for 29 mass lesions and 7 NMLE lesions, respectively.
In mass lesions, traditional morphological or kinetic features were not correlated to malignancy except for fast initial enhancement (P=0.003). The BI-RADS classification produced 100% sensitivity, 40% specificity, 53.3% PPV, 100% NPV and 51.7% overall accuracy. Both the low T2 SI (P=0.05) and low ADC values (P&lt;0.001) significantly correlated with malignancy yeilding improved 86.7%/90.5% specificity and 65.0%/90.5% negative predictive value, respectively (McNemar's test, P&lt;0.01). Combining low T2 SI, ADC values or morphologic or kinetic features did not improve the results.
Conclusion− A single suspective morphologic or kinetic MRI feature is the most sensitive parameter to discover an incidental breast malignancy, as some incidental lesions present with only a few suspicious MRI feature. Specificity of MRI is improved when T2 SI or DWI are addressed.
Citation Format: Arponen O, Sudah M, Masarwah A, Sutela A, Vanninen R. Incidentally detected enhancing lesions found on preoperative breast MRI: Analysis of T2 signal intensity and apparent diffusion coefficient significantly improve classification. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-02-14.
Abstract P4-03-07: Contribution of high-resolution ultrasonography in the diagnosis of non-palpable breast cancer with calcification
Authors: Arai T , Takebe K 
Published: May 2016

Abstract
Background: In diagnosis of non-palpable calcificated breast cancer (NPCBC), stereo-guided mammotome (ST-MMT) serves as the standard. However, ultrasound resolution has improved dramatically recently. We hypothesized that through ultrasonography, it will become possible to diagnose NPCBC by US guided examination such as fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) with much less invasion than ST-MMT.
Method: (Study1) The results of ultrasonic detection ability and US guided examination were studied among the benign lesions of 35 cases and 90 NPCBC patients histologically diagnosed in our facilities from 2010 to 2012. Of the 90 histological types, 74 (82%) were DCIS, and 16 (18%) were invasive carcinoma. (Study 2) The results of 193 progress observation cases from 2008 to 2012 with Birads Category 3 and 4a calcification were examined.
Result: (Study1) Using ultrasonography (Toshiba Aprio XG), calcification was detected in 88 of the 90 NPCBC lesions as echogenic foci. Two non-detectable lesions were DCIS of Van Nuys 1 and Van Nuys 2. The results of the FNAC were 80% positive and 20% indeterminate (there were no negative cases). In the 88 cases of possible calcified substance extracted through FNAC, 99% were confirmed under microscopic observation. (Study 2) 163 of 193 cases were able to be followed-up every six months for two to four years. An increase in calcification was observed in nine cases. Five of these cases were diagnosed with DCIS: Four were Van Nuys 1; one was Van Nuys 2. All five cases were of low-grade-malignancy.
Conclusion: The diagnostic method using FNAC to visualize calcification using high-resolution ultrasonography is an effective method to reduce the non-efficient, invasive breast cancer detecting method of ST-MMT. The diagnostic method is particularly useful in women of small breast size in Asian countries. The few low-grade DCIS cases included were not detected with ultrasound. However, we believe it is not a diagnostic error. As a result, we stopped using the ST-MMT from 2010. In spite of this, in the MMG screening performed in our facilities from 2010 to 2012, the detection rate of NPCBC without mass on MMG was 0.17 %. This detection rate is excellent in our country.
Citation Format: Arai T, Takebe K. Contribution of high-resolution ultrasonography in the diagnosis of non-palpable breast cancer with calcification. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-03-07.
Abstract P4-04-19: Primary breast cancer culture in a perfusion-based bioreactor suitable for in vitro testing of immune blockade therapy
Authors: Muraro MG , Muenst S , Mele V , Spagnoli GC , Oertli D , Weber WP , Soysal SD 
Published: May 2016

Abstract
Introduction: Interaction between cancer cells and immune system critically affects development, progression and treatment of human malignancies. Two-dimensional (2D) in vitro culture systems and in vivo animal models are the primary tools used to test cancer cell response to drugs but they are not suited for the development of immune-mediated therapies. Here we present an innovative method to culture breast cancer tissue in porous 3D scaffolds by using a perfusion-based bioreactor system that allows the maintenance and expansion of tumor microenvironment.
Experimental procedures: Freshly excised breast cancer specimens were fragmented and cultured in a 3D "sandwich-like format" between two layers of porous collagen scaffold under perfusion flow (U-CUP). DMEM/F12, supplemented with 10% autologous human serum, was used as a culture medium. We assessed the ability of tumor and non-malignant cells to survive and expand into the scaffold in perfusion culture, as well as their capacity to recapitulate features of the original breast cancer tissue. The maintenance of immune-infiltrating cells allowed testing of immune blockade therapy in vitro using anti-PD-L1 and anti-CTLA4 antibodies alone or in combination.
Results: The U-CUP culture system preserved tissue viability better compared to a static culture and promoted the expansion of breast cancer cells from surgical specimens together with accompanying stromal and immune cells into the porous scaffold. Tumor tissues were viable after 21 days and mostly recapitulating the initial histology with formation of glands. Administration of anti-PDL1 antibody, alone or in combination with anti-CTLA4, to the culture medium was associated with increased expression of markers of immune-activation (i.e. IFNg) and decreased expression of immunosuppressive cytokine IL10.
Conclusions: Our results show that culture of breast cancer tissue in a 3D perfusion-based bioreactor might represent a promising system for the pre-clinical evaluation of immune-mediated therapies. Preserving malignant, interstitial and immunocompetent cells comprised in surgically excised breast cancer samples might allow a direct evaluation of the effects of various treatments on the complex tumor microenvironment. This engineered in vitro model could be extended as a platform allowing the testing of innovative approaches for the treatment of human malignancies, possibly in the direction of personalized medicine.
Citation Format: Muraro MG, Muenst S, Mele V, Spagnoli GC, Oertli D, Weber WP, Soysal SD. Primary breast cancer culture in a perfusion-based bioreactor suitable for in vitro testing of immune blockade therapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-19.
Abstract P4-04-22: Upregulation of the interleukin 17/granulocyte-colony stimulating factor/fibroblast growth factor axis in breast cancer and its negative association with treatment outcome
Authors: Kawaguchi K , Suzuki E , Yamamoto Y , Saito K , Toi M 
Published: May 2016

Abstract
Background
Interleukin (IL) 17 is secreted by T helper 17 cells and tumor cells. It may induce the proliferation of mesenchymal stem cells (MSCs) in the tumor microenvironment directly and/or via fibroblast growth factor (FGF) and granulocyte-colony stimulating factor (G-CSF) production by tumor-associated macrophages. MSCs play various roles in tumor development and progression, by mediating tumor cell migration, promoting angiogenesis, regulating immune responses, and inducing anti-cancer drug resistance. Therefore, in this study, we examined the association of the IL17/FGF/G-CSF axis with both breast cancer development and response to chemotherapy.
Methods
Eighty-nine breast cancer patients (34% with luminal, 45% with HER2, and 21% with triple-negative breast cancer) and 55 healthy volunteers were analyzed. Serum IL17, basic FGF, and G-CSF levels were measured using a Luminex system. The primary objective was to evaluate the difference in IL17 serum levels between breast cancer patients and healthy volunteers. Secondary objectives were to determine the correlation of IL17 levels with the basic FGF and G-CSF levels, pathological complete response (pCR) (if neoadjuvant therapy was administered), and disease-free survival (DFS) in breast cancer patients. Statistical analyses were performed using the Mann-Whitney, chi-squared, and log-rank tests.
Results
Serum levels of IL17 (median, 91.9 vs. 40.3 pg/ml, p&lt;0.0001), basic FGF (median, 63.9 vs. 3.15 pg/ml, p&lt;0.0001), and G-CSF (median, 61.0 vs. 29.4 pg/ml, p&lt;0.0001) were significantly higher in breast cancer patients than in healthy volunteers. IL17 levels were strongly correlated with basic FGF (r=0.86, p&lt;0.0001) and G-CSF (r=0.73, p&lt;0.0001) levels. Among 64 patients who received neoadjuvant therapy, those with low IL17 levels (&lt;91.9 pg/ml) achieved a significantly higher pCR rate than those with high IL17 levels (≥91.9 pg/ml) (56.0% vs. 25.6%, p=0.014). In addition, the DFS at a median follow-up of 35.7 months was significantly higher in patients with low IL17 levels (p=0.0190).
Conclusion
The IL17/FGF/G-CSF axis was upregulated in breast cancer patients and the levels of these markers were inversely correlated with pCR and prognosis. These results may provide novel insight into the role of IL17 in tumor development and have important implications in the development of IL17 as a target in the treatment of breast tumors.
Citation Format: Kawaguchi K, Suzuki E, Yamamoto Y, Saito K, Toi M. Upregulation of the interleukin 17/granulocyte-colony stimulating factor/fibroblast growth factor axis in breast cancer and its negative association with treatment outcome. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-22.
Abstract P4-08-02: APOBEC3B upregulation by the PKC-NFκB pathway in breast cancer
Authors: McCann J , Leonard B , Starrett G , Kosyakovsky L , Molan A , Burns M , McDougle R , Parker P , Brown W , Harris R 
Published: May 2016

Abstract
Overexpression of the antiviral DNA cytosine deaminase APOBEC3B has been linked to somatic mutagenesis in breast and other cancer. Human papillomavirus (HPV) infection accounts for APOBEC3B upregulation in cervical and head/neck cancers. However, the responsible mechanisms are unclear for non-viral malignancies such as breast cancer. Here, we demonstrate APOBEC3B upregulation through the PKC-NFκB pathway. PKC activation by the diacylglycerol mimic PMA causes specific and dose-responsive increases in APOBEC3B mRNA, protein, and activity levels, which are strongly suppressed by PKC and NFκB inhibition. Induction correlates with RELB (but not RELA) recruitment to endogenous APOBEC3B implicating non-canonical NFκB signaling. Relevance to tumors is supported by PKC inhibitor-mediated APOBEC3B downregulation in multiple breast cancer cell lines. These data establish the first mechanistic link between APOBEC3B and a common signal transduction pathway, suggesting that existing PKC-NFκB inhibitors could be repurposed to suppress cancer mutagenesis, dampen tumor evolution, and decrease the probability of adverse outcomes such as drug resistance and metastases.
Citation Format: McCann J, Leonard B, Starrett G, Kosyakovsky L, Molan A, Burns M, McDougle R, Parker P, Brown W, Harris R. APOBEC3B upregulation by the PKC-NFκB pathway in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-08-02.
Abstract P4-08-07: CDCP1 cleavage is necessary for homodimerization-induced migration of triple-negative breast cancer
Authors: Wright H , Motazedi M , Nelson L , Aulmoli J , Flanagan L , Razorenova O 
Published: May 2016

Abstract
Triple negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks the estrogen, progesterone, and HER2 receptors and is resistant to targeted and hormone therapies. TNBCs express high levels of the transmembrane glycoprotein, CUB-domain containing protein 1 (CDCP1), which has been correlated with the aggressiveness and poor prognosis of multiple carcinomas. Full-length CDCP1 (flCDCP1) can be proteolytically cleaved, resulting in a cleaved membrane-bound isoform (cCDCP1). CDCP1 is phosphorylated by Src family kinases in its full-length and cleaved states, which is important for its pro-metastatic signaling. We observed that cCDCP1, compared to flCDCP1, induced a dramatic increase in phosphorylation of the migration-associated proteins: PKCδ, ERK1/2, and p38 MAPK in HEK 293T. In addition, only cCDCP1 induced migration of HEK 293T cells and rescued migration of the TNBC cell line, MDA-MB-231, expressing shRNA against CDCP1. Importantly, we found that only cCDCP1 is capable of dimerization, which can be blocked by expression of the extracellular portion of cCDCP1 (ECC), indicating that dimerization occurs through CDCP1's ectodomain. Furthermore, we found that ECC inhibited phosphorylation of PKCδ by Src and migration of TNBC cells, indicating that the cCDCP1 dimer is an important contributor to TNBC aggressiveness. These studies have important implications for development of a therapeutic to block CDCP1 activity and TNBC metastasis.
Citation Format: Wright H, Motazedi M, Nelson L, Aulmoli J, Flanagan L, Razorenova O. CDCP1 cleavage is necessary for homodimerization-induced migration of triple-negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-08-07.
Abstract P4-09-01: FGFR1 protein expression is associated with prognosis in primary breast cancer: A comprehensive analysis of gene copy number, mRNA and protein expression
Authors: Tomiguchi M , Yamamoto Y , Yamamoto-Ibusuki M , Yamaguchi R , Fujiki Y , Fujiwara S , Sueta A , Takeshita T , Inao T , Iwase H 
Published: May 2016

Abstract
Background: The Cancer Genome Atlas (TCGA) showed that copy number gain/amplification of FGFR1 was around 10% in primary breast cancer. FGFR1 gene amplification in breast cancer has been reported in some studies, more likely seen in ER-positive subtype. Several preclinical and clinical studies demonstrated that FGFR1 was one of novel targets of therapy for metastatic breast cancer. Previous studies suggested that aberrant FGFR1 expression was associated with poor prognosis, while there was no report that compared copy number aberration, mRNA and protein expression. The aim of this study is to analyze FGFR1 gene copy number, expression levels of FGFR1 mRNA and FGFR1 protein in ER-positive/HER2-negative primary breast cancer, and to examine the relationship between FGFR1 status and clinicopathological parameters including prognosis.
Methods: The cohort of this study included 307 ER-positive/HER2-negative primary invasive breast cancer patients treated with standard care at Kumamoto University Hospital between June 2000 and January 2011. We performed a comprehensive analysis of FGFR1 at the levels of gene copy number, mRNA and FGFR1 protein expression analyzed by qPCR, qRT-PCR and immunohistochemistry, respectively.
Results: FGFR1 gain/amplification was identified in 43 (14.0%) out of 307 patients. FGFR1 gain/amplification had significantly associated with higher nuclear grade (p=0.010). No correlations between FGFR1 mRNA expression levels and any clinicopathological factors were found. Expression levels of FGFR1 protein was positively associated with invasive tumor size (p=0.039). Modest positive correlations between these three (FGFR1 gene gain/amplification, expression levels of FGFR1 mRNA and FGFR1 protein) were found. The univariate analysis revealed that high FGFR1 protein expression was significantly related to poor prognosis (p=0.0019, HR: 2.63, 95%CI: 1.17-5.98) in terms of relapse-free survival (RFS) but not breast cancer-specific survival. The univariate analysis did not show that any factors except FGFR1 protein expression were significantly associated with RFS in this cohort.
Conclusion: Expression levels of FGFR1 protein may be an independent prognostic factor in terms of RFS for ER-positive/HER2-negative breast cancer patients receiving standard care.
Citation Format: Tomiguchi M, Yamamoto Y, Yamamoto-Ibusuki M, Yamaguchi R, Fujiki Y, Fujiwara S, Sueta A, Takeshita T, Inao T, Iwase H. FGFR1 protein expression is associated with prognosis in primary breast cancer: A comprehensive analysis of gene copy number, mRNA and protein expression. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-01.