bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scoring system to predict under-evaluation in patients diagnosed with benign papilloma at ultrasound-guided core needle biopsy (CNB).
Authors: Ko E , Han W , Lee J , Kim E , Moon H , Yu J , Noh D 
Published: December 2010

Abstract
Abstract #2001
Background: The aim of this study was to determine factors that predict under-evaluation of atypical lesion or malignancy in patients diagnosed with benign papilloma at ultrasound-guided core needle biopsy (CNB), and to develop a prediction algorithm for scoring the possibility of a diagnosis upgrade to atypical lesion or malignancy based on clinical, radiological and pathological factors. Methods: The study enrolled patients diagnosed with benign papilloma at ultrasound-guided CNB who subsequently underwent surgical excision of the lesion. Multivariate analysis was used to identify relevant clinical, radiological and pathological factors that may predict malignancy. Results: A total of 262 patients with benign papilloma at CNB were identified. Of the 110 patients who underwent subsequent surgical excision, 22 (20%) were diagnosed with atypical papilloma or malignancy. Multivariate analysis revealed that mass or calcification on mammography, size on imaging &gt;15 mm, peripheral location, and a palpable lesion were independent predictors of malignancy. A scoring system was developed based on logistic regression models and beta coefficients for each variable. The area under the ROC curve was 0.868 (95% CI: 0.794-0.941), and the negative predictive value was 100% for a score of 0 or 1 (Of the 110 patients, 58 patients had the score of 0 or 1). Conclusions: A scoring system to predict malignancy in patients diagnosed with benign papilloma at CNB was developed based on four factors: peripheral location, palpable lesion, mass or calcification on mammography, size on imaging. This system was able to identify a subset of patients with lesions likely to be benign, indicating that imaging follow-up rather than surgical excision may be appropriate.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2001.
Using custom protein microarrays to identify autoantibody biomarkers for the early detection of breast cancer.
Authors: Anderson KS , Sibani S , Wong J , Hainsworth E , Mendoza EA , Eugene R , Raphael J , Logvinenko T , Ramachandran N , Godwin A , Marks J , Engstrom P , LaBaer J 
Published: December 2010

Abstract
Abstract #2003
Background: Cancer patients make antibodies to tumor-derived proteins that are potential biomarkers for early detection. To detect autoantibodies to tumor antigens in patient sera, we have adapted novel high-density custom protein microarrays (NAPPA) expressing 6,500 candidate tumor antigens for biomarker detection. These arrays are probed with sera from patients with early stage breast cancer and healthy women. Using this approach, we identified antibodies in the sera of breast cancer patients.&#x2028; Methods: 6,500 full-length human antigens were expressed using mammalian reticulocyte lysate and captured onto NAPPA protein microarrays. Protein expression (&gt;90%) was confirmed with anti-GST antibodies. Patient sera were added, and bound IgG detected with secondary antibodies. Serum samples were obtained from 103 patients with stages I-III breast cancer, and 103 age-matched control women, all undergoing routine mammography.&#x2028; Results: Using high-density protein microarrays, sera from breast cancer patients (n=53) and healthy donor sera (n=53) were screened for autoantibodies to 6,500 protein antigens. Antigens were selected for further analysis if the 95th percentile of signal of cases and controls were significantly different (p&lt;0.05) and if the number of cases with signals above the 95th percentile of controls was larger than the number expected due to random chance (p&lt;0.05). Known tumor antigens, such as p53, were detected, as well as novel antigens such as DCC1, Rab7L and USP44. In total, 768 unique antigens were selected for further analysis with an independent set of breast cancer patient (n=50) and healthy donor sera (n=50).&#x2028; Conclusions: Custom in-situ protein microarrays can be used to detect serum tumor antigen-specific antibodies and enables the rapid, simultaneous detection of immunogenic tumor antigens from patient sera. These autoantibodies are being evaluated as potential biomarkers for the early diagnosis of breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2003.
Evaluation of human secretoglobins and MIC-1 as serum diagnostic biomarkers for breast cancer.
Authors: Bistrup A , Cabaltica C , Jalilie M , Wolfert RL , Kim NW 
Published: December 2010

Abstract
Abstract #2005
Using microarray and quantitative RT-PCR analysis, we found mRNA corresponding to several members of the human secretoglobin family and MIC-1 to be highly expressed in various cancer tissues, as compared to the corresponding normal tissues. Our target ECM2, known in the literature as Lipophilin B (LipB), was found to be upregulated in endometrial, uterine, breast and prostate cancer tissues. Our target ECM3, also known as Mammaglobin B (MamB) or Lipophilin C, was found to be upregulated in endometrial and uterine cancer tissues. DD-X065, also known in the literature as macrophage inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor-beta (TGF-b) family, was found to be upregulated in breast, colon, lung, ovarian, and prostate cancer tissues.&#x2028; There is considerable evidence suggesting that members of the secretoglobin family exist predominantly as heterodimers and higher order complexes. Mammaglobin A (MamA) protein has been found to be present in breast tissue in a complex with LipB protein. We generated a series of mouse monoclonal antibodies directed against different complexes composed of members of the family, including MamA, LipB, and MamB. Employing these specific antibodies, we have developed sensitive immunoassays to measure serum levels of several of the complexes.&#x2028; In the current study, we evaluated serum from breast cancer patients for levels of two secretoglobin family complexes: MamA/LipB and MamB/LipB, as well as for MIC-1, utilizing our previously established ELISA assay2.&#x2028; The study comprised serum samples from 150 normal healthy individuals and 250 breast cancer patients. The sensitivity and specificity of the assays for detection of breast cancer were quantified by receiver operating characteristic (ROC) analysis. Compared to normal healthy individuals, the median serum concentrations of MamA/LipB was increased by approximately 2.8 fold in breast cancer, irrespective of stage. ROC analysis of breast cancer patients versus normal healthy individuals resulted in an AUC of 0.67 in all stages. For MamB/LipB, the median serum concentration in cancer serum was increased over normals by approximately 1.8 fold and the corresponding AUC was 0.62. The median serum concentration for MIC-1 in cancer serum was increased over normals by approximately 1.1 fold and the corresponding AUC was 0.61. The sensitivity of the MIC-1 assay was greater than that of any of the secretoglobin family complex assays at 90%, 95% and 98%.&#x2028; Our study suggests that MIC-1 and members of the secretoglobin family may be promising serum markers for breast cancer. Their utility may be improved when used in combination with other novel diagnostic biomarkers. Further studies are underway to validate the clinical potential of this family of markers.&#x2028; 2Bistrup, A, et al., (2007) Proceedings of 98th AACR Annual Meeting, Los Angeles, CA.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2005.
CDK2 is required for LMW-cyclin E mediated murine mammary tumorigenesis.
Authors: Akli S , Van Pelt CS , Bui TN , Keyomarsi K 
Published: December 2010

Abstract
Abstract #2007
Cyclin E is a regulatory protein with multiple functions that activates CDK2, controls centrosome duplication, and regulates histone gene transcription. Our previous studies have shown that the presence of Low-molecular-weight (LMW) forms of cyclin E correlates strongly with decreased survival in patients with breast cancer. Transgenic mice overexpressing LMW cyclin E had increased incidence of mammary tumors and distant metastasis when compared to full length cyclin E. The critical role of LMW cyclin E in mammary tumorigenesis may be the result of the ability of LMW cyclin E to bind and activate the cyclin-dependent kinase 2 (CDK2). To specifically test the importance of LMW cyclin E-associated CDK2 kinase activity in mammary tumorigenesis, we generated double and triple transgenic mice LMW cyclin E-T1;CDK2-/-, and LMW cyclin E-T1;p53+/-;CDK2-/-. We found that: (i) The development of the mammary glands proceeds relatively normally in these animals demonstrating that CDK2 kinase activity is largely dispensable for mammary gland development; (ii) These mice were resistant to breast cancers initiated by LMW cyclin E overexpression. Whereas LMW-cyclin E-T1 mice in CDK2+/- or CDK2+/+ background succumb to mammary tumors with mean latencies of 16 and 19.5 months respectively, their LMW cyclin E-T1; CDK2-/- littermates do not form mammary tumors up to 24 months (P=0.05 CDK2+/+ versus CDK2-/-; P=0.0252 CDK2+/- versus CDK2-/-; P=0.1457 CDK2+/+ versus CDK2+/-, Log rank test). Similarly, while MMTV-LMW cyclin E-T1/p53+/- transgenic mice in CDK2+/- or CDK2+/+ background succumb to mammary gland tumors between 7 and 13 months with 100% penetrance, their MMTV-LMW cyclin E-T1;p53+/-; CDK2-/- littermates are resistant to tumor formation (P&lt;0.01 CDK2+/+ versus CDK2-/-; P=0.011 CDK2+/- versus CDK2-/-, P=0.5072 CDK2+/+ versus CDK2+/-, Log rank Test). In fact none of the CDK2-/- mice developed mammary tumors when crossed with cyclin E LMW transgenic mice. However, 2 out of the 12 MMTV-LMW cyclin E; p53+/-; CDK2-/- mice generated salivary gland tumors. Hence, these LMW cyclin E; p53+/-; CDK2-/- are susceptible to LMW cyclin E induced salivary tumors in the absence of CDK2. We concluded that CDK2 is critically required for LMW cyclin E induced mammary tumorigenesis and consequently, the loss of CDK2 renders CDK2-/- mice resistant to breast cancer induced by LMW cyclin E expression. In clear contrast to mammary epithelial cells, we found that in salivary gland cells LMW cyclin E continued to elicit malignant transformation even in the absence of CDK2. Our work suggests that due to the requirement of CDK2 for LMW-cyclin E mediated mammary tumorigeneis, these tumors are prime candidates for anti-CDK2 therapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2007.
Preservation of lymphatic drainage from arm in breast cancer surgery: is it safe?.
Authors: Kang S , Choi J , Jeon Y , Lee S , Bae Y 
Published: December 2010

Abstract
Abstract #201
Purpose: Sentinel lymph node biopsy (SLNB) for breast cancer was introduced to prevent the high morbidity seen with Axillary lymph node dissection (ALND). Although multiple comparison studies have confirmed that SLNB consistently has lower morbidity and lymphedema rates than ALND; it is still clinically significant ranging from 0∼13%. The aim of this study was to confirm the feasibility of the technique, so called Axillary reverse mapping (ARM), and to test the hypothesis that arm lymphatics are never involved by the metastatic process of breast cancer.&#x2028; Methods: We reviewed prospectively maintained database of 129 patients who operated for primary breast cancer since June 2007. Sentinel lymph nodes (SLNs) were identified by using a radiolabeled isotope (TC99m-phytate or human serum albumin). Under general anesthesia, 2.5∼3 mL of blue dye was injected in the upper inner arm along the medial intramuscular groove of ipsilateral arm in order to locate the draining lymphatics or lymph node from the arm. We then proceeded as usual with the SLNB or ALND. During axillary procedure, we take the blue node (ARM node) and SLN (hot node), and both were sent to pathology department for frozen section analysis. If SLNs were positive, ALND was performed and axillary contents were sent to pathology. Histological results of ARM node were compared with that of the other nodes of the SLNB or ALND.&#x2028; Results: The mean age of patients was 48.3 years old (rang 27∼73). Surgeries included 41 mastectomies, 80 breast conserving surgeries and eight skin sparing mastectomies with immediate reconstruction. Of the 129 procedures, 81 were in SLNB (62.8%), 43 SLNB+ALND (33.3%), and five ALND. One hundred one of 129 (78.3%) blue ARM nodes were identified in the axilla. The average number of removed ARM node was 1.5 (range 1∼5). In 19 of 96 SLNB cases, the ARM nodes were hot, yielding 18.9% of concordance rate between ARM node and SLN. Among these 19 cases, seven ARM nodes contained metastasis. In one SLNB case, the metastatic ARM node was not hot. In all five ALND cases, ARM nodes were identified and one of five ARM nodes was positive for metastasis. Thus, ARM node metastasis rate of identified ARM node during ARM procedure was 8.9% (9/101).&#x2028; Conclusion: According to our study, it is thought that lymphatic drainage from arm share common lymphatic channel in axilla with lymphatic flow from breast. Therefore, intentional preservation of lymphatics or lymph node drained from arm during performing axillary surgery in breast cancer could be a dangerous one.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 201.
Antitumor activity of chemoendocrine therapy in premenopausal (capecitabine [CAP] + tamoxifen [TAM]) and postmenopausal (CAP + letrozole [LET]) human breast cancer [BC] xenograft models.
Authors: Kataoka M , Yamaguchi Y , Sawada N , Moriya Y , Evans DB , Yasuno H , Mori K , Hayashi S 
Published: December 2010

Abstract
Abstract #2012
Background: The preferential treatment for estrogen receptor (ER)-positive metastatic or recurrent breast cancer is endocrine therapy unless it is life-threatening. CAP, an oral fluoropyrimidine, is activated to 5-FU by thymidine phosphorylase (TP) in tumors. We have evaluated the efficacy of endocrine therapy in combination with CAP in premenopausal and postmenopausal ER-positive human BC xenograft models.&#x2028; Methods: In a premenopausal BC model, ER-positive MCF7 cells were subcutaneously (sc) inoculated into nude mice which had been implanted sc with 0.25 mg 17β-estradiol pellets. The mice received 6 weeks oral therapy with vehicle, CAP (days 1-14, every 3 weeks) at the maximal tolerated dose (MTD) of 539 mg/kg or 2/3 MTD +/- TAM at 100 or 30 mg/kg/day. In a postmenopausal BC model, nude mice were ovariectomized and implanted sc with 1.5 mg androstenedione pellets the day before tumor cell inoculation. MCF7A25F3 cells, an aromatase gene transfectant of MCF7, were inoculated sc into the mice. The mice received 6 weeks' oral administration of vehicle, CAP (days 1-14, every 3 weeks) at 2/3 MTD +/- LET at 0.1 mg/kg/day. TP level in tumors was measured on the final day of the first treatment cycle by ELISA. In vitro ER reporter gene assays were performed by co-culturing MCF7 cells transfected with estrogen response element-GFP gene with stromal cells isolated from human BC tissues. Testosterone was added to the culture medium as a substrate for aromatase and the expression of GFP was measured.&#x2028; Results: In the premenopausal model, the antitumor activity of the combination therapy with CAP and TAM was significantly superior to that of each monotherapy (p&lt;0.001). In the postmenopausal model, the antitumor activity of the combination therapy with CAP and LET was also significantly superior to that of each monotherapy (p&lt;0.05). No augmentation of toxicity in terms of body weight loss was observed with the combination therapy in each xenograft model. In the premenopausal model, the tumor levels of TP were up-regulated (p&lt;0.05) by TAM treatment indicating that TAM might potentiate the antitumor activity of CAP. On the other hand, the tumor levels of TP remained unchanged by LET treatment in the postmenopausal model. In ER reporter gene assays, GFP expression was decreased by the addition of either 5'-deoxy-5-fluorouridine (5'-DFUR, an intermediate of CAP), 4-hydroxytamoxifen (4-OHT, active form of TAM) or LET in a concentration-dependent manner. 5'-DFUR showed at least additive inhibitory effect in combination with 4-OHT or LET.&#x2028; Conclusion: Chemoendocrine therapy using CAP might be a useful treatment modality for BC patients regardless of the menopausal status.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2012.
The role of receptor tyrosine kinase and activated PI3K signaling in response/resistance to HER-2 targeted therapy.
Authors: O'Brien NA , Browne BC , Chow L , Ginther C , Bensadigh B , Arboleda J , Duffy MJ , Crown J , O'Donovan N , Slamon DJ 
Published: December 2010

Abstract
Abstract #2013
Background: Trastuzumab and lapatinib therapy provide proven clinical benefits to women with HER-2 positive breast tumors. However, not all patients that have high HER-2 levels respond. Here we describe the development and characterization of models of both clinical forms of trastuzumab resistance, i.e., de novo and acquired resistance.&#x2028; Materials and Methods: Models of acquired resistance were established by culturing BT-474 and SKBR3 cells in high dose trastuzumab (105 μg/ml) for nine months. De novo resistance was examined in a panel of 17 HER-2 amplified cell lines. Response to the dual EGFR-HER2 inhibitor, lapatinib, was also measured. For each agent, response was measured by two independent assays; cell count and colony formation assay. Levels of HER-2, p-HER-2, EGFR, p-EGFR, IGF-1R, p-IGF-1R, p95, PTEN, and p27, and the presence of PIK3CA activating mutations were assessed in each cell line.&#x2028; Results: Both BT-474 and SKBR3 conditioned cell lines have a reduced response to trastuzumab but remain sensitive to lapatinib. Analysis of the panel of HER-2 amplified cell lines revealed that SUM-225, HCC-1419, HCC-1954, HCC-1569 and JIMT-1 are models of de novo resistance to trastuzumab. The SUM-225 and HCC-1419 cell lines, despite being trastuzumab resistant, were exquisitely sensitive to lapatinib. The UACC-893, UACC-732, HCC-1569, MDA-MB-361 and JIMT-1 cell lines were identified as being resistant to lapatinib (IC50 &gt; 1 μM), whereas the HCC-1569 and JIMT-1 were resistant to both trastuzumab and lapatinib. Resistance to trastuzumab correlated significantly with active PI3K signaling (p = 0.003), as assessed by combined analysis of PTEN status and PIK3CA mutation status. Response to lapatinib correlated significantly with levels of HER-2 (p = 0.013), pHER-2 (p = 0.086), p95 (p = 0.033), p-EGFR (p = 0.019) and p-IGFR (p = 0.046).&#x2028; Conclusion: We have identified reliable, HER-2 overexpressing, cell line models of response and resistance to trastuzumab and lapatinib. Our analysis of these models indicates that activated PI3K signaling plays a crucial role in de novo resistance to trastuzumab while high levels of RTK signaling appears to sensitize HER-2 positive cells to lapatinib treatment.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2013.
Ixabepilone plus capecitabine improves progression free survival in patients with metastatic breast cancer resistant to taxanes: a pooled analysis from two phase III trials.
Authors: Roche H , Li R , Ro J , Vrdoljak E , Rahman ZU , Medina C , Conte P , Volles LA , Poulart V , Sparano JA 
Published: December 2010

Abstract
Abstract #2015
Background:&#x2028; Patients (pts) with MBC whose tumors are resistant to taxanes (T) have limited therapeutic options. Ixabepilone (ixa), the first in a new class of antineoplastic agents, showed clinical benefit in combination with capecitabine (C) in 2 large clinical trials in metastatic breast cancer (MBC) pts resistant to (study 046, JCO, 2007), or pretreated with anthracycline (A) and T (study 048). Pts whose tumors were resistant to A/T were also allowed to enter the 048 trial. In 048, ixa + C, compared to C alone, also demonstrated significant increases in progression-free survival (PFS, HR 0.79 [0.69-0.90)]) and ORR (43% vs 29%). A trend toward increased OS was seen both in 048 (HR 0.90 [0.78-1.03]) and in 046 (HR 0.90 [0.77-1.05]), which did not reach statistical significance. Here we present a pooled analysis from the 2 studies of clinical outcomes (ORR, PFS, and OS) in patients with a strict definition of resistance to T.&#x2028; Methods:&#x2028; 1973 pts with MBC previously treated with an A and T, were randomized in phase III trials to receive either ixa (40 mg/m2 IV over 3h Q3w) + C (1000 mg/m2 PO BID x14d Q3w) or C alone (1250 mg/m2 PO BID x14d Q3w). For both studies, resistance was defined as disease progression up to 4 months following T in the metastatic setting and up to 12 months following adjuvant T therapy. Due to the similarity of the study populations, individual pt data from both studies was pooled to better evaluate treatment effect within pre-planned patient subgroups.&#x2028; Results:&#x2028; 1337 pts from the 2 studies were T resistant and randomized to ixa + C or C alone. ORR and PFS favored ixa + C in this pt population, and there was a trend towards increased OS, which did not reach statistical significance (see table).&#x2028; &#x2028; Conclusion:&#x2028; Ixa + C is the first combination to show a clinical benefit of PFS in pts with MBC resistant to T (following a strict definition of resistance). The benefit seen in this pooled analysis was consistent with that observed in the resistant pt population from the individual studies as well.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2015.