bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic resonance imaging and ultrasonography in predicting pathologic extent after preoperative chemotherapy in stage II-III breast cancer.
Authors: Guarneri V , Pecchi A , Torricelli P , Piacentini F , Frassoldati A , Mauri C , Battista R , Canossi B , D'Amico R , Conte P 
Published: December 2010

Abstract
Abstract #4024
Introduction and aims: the main advantage of preoperative chemotherapy (PCT) is tumor down-staging, that can allow either mastectomy in large, inoperable primaries, or breast conserving surgery (BCS) for patients initially candidate to mastectomy. Therefore, an accurate measurement of residual disease after PCT is critical in the optimal surgical planning. Aim of this study is to evaluate the accuracy of breast magnetic resonance imaging (MRI) and ultrasonography (USG) in predicting the extent of breast residual disease.&#x2028; Patients and Methods: patients with stage II-III invasive breast tumor receiving PST and imaged with post-treatment MRI, USG or both were included; deltas were calculated as differences between the longest tumor diameter as measured by MRI and USG and the pathologic size of residual breast tumor. Differences between deltas were tested by using T test for paired data.&#x2028; Results: 45 patients treated with PCT in our Institution were eligible. Patients characteristics were as follows: mean age 50 yrs (range 30-70 yrs); stage IIA 31%, IIB 49%, IIIA-B: 20%. Eighty-nine % of the cases had ductal histology, 69% had ER positivity, and 24% had HER2 over-expression. The mean T size at diagnosis was 3.8 cm (range 1.5-8 cm). PCT type was anthracycline-based (24%) or anthracycline-taxane combination (76%). Forty-four patients have been evaluated after PCT by MRI, 41 by USG, 40 patients by both MRI and USG. The mean T size (range) after PCT was 2 cm (0-6.5 cm) and 1.7 cm (0-5 cm) as measured by MRI and USG respectively. The mean interval between breast imaging and surgery was 20 days (range 1-63). Type of surgery was mastectomy in 45% and BCS in 55% of the cases; 6 patients (13%) achieved a pathologic complete response (pCR). The mean pathologic T size was 1.98 cm (range 0-6 cm). The mean of the deltas were 0.04 (SD 1.91) and -0.19 (SD 1.53) for MRI and USG respectively (p=0.22). A complete response by MRI was observed in 9 cases: 3 cases were confirmed as pCRs; 2 cases presented with scattered microscopic residual disease. An USG complete response was observed in 8 cases (4 confirmed pCRs).&#x2028; Conclusion: in this series of patients, MRI and USG do not show significant differences in predicting the breast residual tumor after PCT. The major challenge for breast imaging after PCT is represented by scattered residual disease.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4024.
Apocrine carcinoma of the breast: clinical presentations, multimodality imaging findings and pathologic correlation.
Authors: Woo O , Kim A , Cho K , Seo B , Kang E 
Published: December 2010

Abstract
Abstract #4029
Background : &#x2028; Apocrine carcinoma (AC) of the breast is a rare malignant tumor and is lack of standardized criteria for the diagnosis. Thus clinicopathological features and radiologic findings have not been determined. We retrospectively analyzed the clinical presentation and the multimodality imaging findings of mammography, ultrasography and MRI and correlated with pathologic results.&#x2028; Materials and Methods : &#x2028; We retrospectively examined data on 850 patients who had been surgically treated for primary breast carcinoma between 2003 and 2008. Among them, there were 10 cases with the diagnosis of apocrine carcinoma.&#x2028; Ten patients underwent mammography and ultrasonography and six patients underwent MR imaging. Eight patients underwent pre-operative US-guided core needle biopsy. We analyzed the radiologic findings and pathologic results.&#x2028; Results : &#x2028; The present study showed that the frequency of apocrine carcinoma was 1.2%. Almost all patients were symptomatic and painless lump was the most common complaint. Patient ranged in age from 38 to 62 year (mean, 50.5 years). The mean lesion size was 1.9cm (range, 1.1-3.5cm).&#x2028; Common imaging features were as follows: mass or focal asymmetry without microcalcifications (n=7), mass with microcalcifications (n=3) on mammography; a mass with an round to irregular shape (n=9), indistinct-margin(n=8) on ultrasonography. On six dynamic contrast-enhanced MRI, enhancing masses in 3, mass with spotty nodular enhancement adjacent to the tumor in 3, which showed rapid enhancement and delayed washout pattern in five cases and plateau enhancement pattern in one case. Specifically, 3 patients had unilateral multifocal cancer. Two patients showed ipsilateral axillary lymphadenopathy.&#x2028; Pathologic examination revealed AC (n=3), AC with apocrine carcinoma in situ (n=3), apocrine carcinoma in situ (n=1) and, AC with intraductal component and EIC positivity (n=3). Mass with spotty nodular enhancement on MRI was correlated with intraductal component and EIC positivity.&#x2028; Conclusion : &#x2028; The radiologic findings of apocrine carcinoma of the breast are not specific. Occasionally, apocrine carcinoma shows mass with spotty nodular enhancement adjacent to the tumor on MRI and this finding is correlated with intraductal component and EIC positivity.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4029.
Notch-1 expression is not related to the percentage of CD326+ cells in bone marrow aspirates of patients with primary breast cancer.
Authors: Lee B , Li C , Lucci A , Cohen EN , Gao H , Krishnamurthy S , Ueno NT , Hortobagyi GN , Cristofanilli M , Woodward WA , Reuben JM 
Published: December 2010

Abstract
Abstract #4030
Background: The presence of epithelial cells (CD326+CD45dim) in the bone marrow (BM), i.e. disseminated tumor cells (DTC), are related to poor prognosis of primary breast cancer (PBC). Notch signaling pathway is involved in the development of the breast and aberrant activation of Notch signaling is an early event in breast cancer. Others have shown that breast cancer stem cells (BCSC) with the putative phenotype of CD44+CD24- can be identified within cell lines and primary tumor and have upregulated genes including Notch-1. However, it is unclear if Notch-1 is highly expressed by DTC and BCSC in BM of patients with PBC. We hypothesized that the Notch-1 expression is correlated with the level of BCSC within DTC. In this study, we enumerated BCSC in DTC-enriched populations in patients with PBC and assessed the expression of Notch-1 by RT-PCR.&#x2028; Methods and Patients: As part of an ongoing prospective study, from September 2006 to May 2008, 121 BM aspirates were collected from as many patients with PBC. Thirty-seven patients, median age of 52 years (range, 30-76 years), provided BM aspirates under anesthesia at time of surgery. At the time of BM collection, 9 patients had received neoadjuvant therapy. BM mononuclear cells (BMC) were enriched for DTC using anti-CD326 antibody-coated magnetic beads, and isolated using the AutoMACS-Pro cell separator system. DTC and BCSC were identified by multi-color FACS analysis. Thereafter, DTC-enriched cell preparations were analyzed for expression of ER, PR, HER-2, Notch-1, and Numb by RT-PCR; level of each transcript was normalized to a ratio to the house keeping gene GAPDH.&#x2028; Results: The mean ± SEM DTC in BMC was 1.05 % ± 0.09% and the majority was BCSC (79.7% ± 1.87%). The proportion of DTC-enriched fractions that expressed Notch-1, Numb, ER, PR, and HER-2 transcripts was 27/37 (73.0%), 33/37 (89.2%), 24/37 (64.9%), 15/37 (40.5%), and 20/37 (54.1%), respectively. The expression of Notch-1, Numb, ER, PR, and HER-2 transcripts did not correlate with the percentage of DTC. Contrary to our hypothesis, Notch-1 and Numb mRNA expression in DTC-enriched cells negatively correlated with the percentage of BCSC (Spearman's rho = -0.384, p= 0.027; and rho= -0.347, p= 0.048, respectively).&#x2028; Conclusions: Our results show no correlation between the level of Notch-1 expression and the percentage of BCSC in DTC-enriched populations in BM of patients with PBC. Since these studies were conducted in CD326-enriched populations, it underscores the necessity to further purify the CD44+CD24- cells and conduct studies in isolated single cells to definitively delineate the gene expression of BCSC from patients with PBC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4030.
The insulin-like growth factor receptor I status in luminal A breast carcinoma.
Authors: Ben Hamida A , Sircoulomb F , Beckhouche I , Chaffanet M , Bertucci F , Birnbaum D , Jacquemier J 
Published: December 2010

Abstract
Abstract #4034
Background: The IGF-IR overexpression is reported to be detectable in 43-50% of primary breast cancers, its clinical and prognostic significance remains undetermined. Insulin growth factor type I (IGF-IR) is induced by estrogens in estrogens receptor (ER) positive cells that could explain why the IGF-IR overexpression is strongly related to ER positive breast cancer. However a small proportion of ER/PR negative cases overexpressed IGF-IR. The aim of this study was to correlate IGF-IR status by three techniques on a series of breast carcinomas : DNA microarrays ,CGH arrays and Immunohistochemistry.&#x2028; Material and Methods: Immunohistochemical phenotypes were studied in a series of 72 cases of breast carcinoma (40 basal and 32 luminal A). A series of 13 Markers was also studied IGF-IR, ER, PR, AR441, bcl2, FoxA1, Ki67, Gata3, P53, EGFR, ERBB2, CAV1 and MS110(BRCA1). Gene expression profiling with DNA microarrays (Affymetrix) and 244k CGH microarray was done on the same cases.&#x2028; Results: The IGF-IR expression was observed in IHC in 61% of the cases, overexpression in 25% and Gain or amplification in 7% .The IHC IGF-IR positivity was strongly correlated to the IGF-IR expression ( R=0.28 p&lt;0.016) and IGF-IR DNA status (R=0.53 p= 5.610-6 ). IGF-IR over-expression in DNA microarrays is the only one results to be strongly associated to the luminal A subtype : 15/18 of the over expressed cases p=1.56 e-7. However the IHC expression of the ER related biomarkers is significantly associated to the IGF-IR overexpression.&#x2028; &#x2028; Discussion: The IGF-IR overexpression is representative of the Luminal A subtype, and to the ER regulated gene in IHC. Exploration of a panel of IGF-IR antibody is mandated before to best evaluate this target gene in IHC, who could contribute to the hormonal response.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4034.
Pure apocrine carcinomas of the breast express ER-alpha 36, a novel alternatively spliced variant of human estrogen receptor-alpha (ER-alpha 66).
Authors: Gatalica Z , Deng H , Lee LM , Wang Z 
Published: December 2010

Abstract
Abstract #4035
Background: Pure apocrine carcinomas (PACs) are defined as tumors composed entirely of epithelium showing apocrine differentiation (large cells with prominent eosinophilic, flocculent cytoplasm with sharply defined borders and large nucleus with prominent macronucleolus). PACs do not express classic estrogen receptor alpha (ER-α66) or progesterone receptor (PR) but consistently over-expresses androgen receptor (AR). We have investigated expression of a novel alternatively spliced variant of ER-α66, named ER-α36, which we recently identified and cloned (Wang ZY et al, PNAS 2006;103: 9063) and demonstrated that it mediates membrane initiated steroid signaling (MISS). MISS is dependent on ER interaction with receptor tyrosine kinases, and we hence investigated co-expression of ER-α36 with EGFR and HER2 in PACs.&#x2028; Methods: 17 patients with breast PAC were studied for expression of ER-α66, PR, AR, HER-2, EGFR and ER-α36 using immunohistochemical methods. ER-α36-specific antibody was custom-made by the Alpha Diagnostic International (San Antonio, TX) against the unique 20 amino acids at the C-terminal of the ER-a36; other antibodies were from commercially available sources. Mammary carcinoma cell line (MDA-MB-231) that lacks expression of ER-α66 but expresses ER-α36 and EGFR, was used as a positive control.&#x2028; Results: All tumors showed characteristic steroid receptor expression profile of apocrine carcinomas (ERα66 and PR negative; AR strongly positive). ERα36 expression was detected in 16/17 cases (94%) in membranous and cytoplasmic distribution. Co-expression of ER-α36 with either one of the tyrosine kinase receptors (HER2 or EGFR) was detected in 16 cases (100% of ER-α36 positive PACs). In an experimental model (MDA-MB-231 cells), 17β-estradiol (E2) strongly induced rapid phosphorylation of the MAPK/ERK1/2, but had only a weak effect in ER-α36 siRNA knock-down MDA-MB-231 cells.&#x2028; Conclusion: Despite the lack of classic full length ER-alpha expression (ER-α66) in PACs, a novel alternatively splice variant (ER-α36) is commonly expressed in this aggressive tumor type. This receptor variant is capable of strong E2 signal transduction and responsible for an increased cell growth. This non-genomic estrogen signaling probably involves membranous interaction between a tyrosine kinase receptor (EGFR or HER2) and ER-α36, resulting in activation of mitogen activated protein kinase pathway.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4035.
Histologic markers of mammographic breast density: core-needle biopsy tissue from healthy volunteers.
Authors: Ghosh K , Brandt KR , Reynolds CA , Watson DA , Lingle WL , Pankratz VS , Hartmann LC , Vachon CM 
Published: December 2010

Abstract
Abstract #4037
Background: Mammographic breast density is a strong and consistent risk factor for breast cancer. Women with dense tissue in over 60 to 75% of the breast are at 4 to 6 times greater risk than women with little or no density. However, the biology of breast density is not well understood and studies at the tissue level are limited. We present the first report of a tissue-based study of breast density, sampling mammographically dense and non-dense areas of the breast of healthy women with the goal of examining histologic correlates.&#x2028; Materials and Methods: Healthy women volunteers aged 40 to 85 years, with no breast symptoms, normal screening mammogram within 6 months, and no personal history of breast cancer were considered eligible. Women with breast-related symptoms, those on endocrine therapy, or with bleeding tendencies were excluded from participation. Sixty consecutive eligible women were enrolled in the study- results are based on the first 34 participants. Eligible women underwent an ultrasound-guided, core-needle breast biopsy of mammographically dense and non-dense areas of the breast, performed by a single experienced radiologist. Quantitative assessment of breast tissue from dense and non-dense areas was performed for epithelium, stroma, and fat. In addition, we assessed the difference in the extent of lobular involution (complete, partial and none) between dense and non-dense areas. We used means and SD to describe distributions in each tissue type. Signed rank test was used to assess within woman differences between dense and non-dense tissue.&#x2028; Results: The mean age of the participants was 50.1 years (range 40 to 79 years). The histological findings are outlined below.&#x2028; &#x2028; Dense tissue is comprised of increased stroma and epithelium and decreased fat, consistent with prior reports on breast density. The finding of 'no involution' was greater in dense tissue compared to non-dense tissue (24% versus 8.8%); non-dense tissue had greater proportion of complete involution compared to dense tissue (82.5% versus 35.2%).&#x2028; Discussion: This report is the first to quantify histology in tissue sampled from dense and non-dense regions of the healthy breast. We find a dramatic difference in tissue composition between dense and non-dense tissue in the breast. Future studies using this tissue to assess molecular markers will further help to characterize pathways through which density may increase breast cancer risk.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4037.
The relationship between tumour NF-kB expression, hormone status, and clinicopathological factors in primary invasive breast cancer.
Authors: Tannahill CL , Obondo C , Al-Murri AM , Doughty JD , Lannigan A , Wilson CR , McMillan DC , Edwards J 
Published: December 2010

Abstract
Abstract #4038
Breast cancer is one of the most common and lethal malignancies in the UK. Conventionally, prognosis is based on hormone status, tumour size, grade and lymph node involvement. Recently it has been proposed that Nuclear Factor Kappa B (NF-kB) is associated with breast cancer development and progression (1). The aim of the present study was to examine the relationship between NF-kB, hormone status and clinicopathological factors in primary invasive breast cancer.&#x2028; Immunohistochemistry was performed on 168 breast tumour sections, with full clinicopathological characteristics. Antibodies were directed against total NF-kB and NF-kB phosphorylated at serine 536 (phospho NF-kB). Two observers independently scored expression using the weighted histoscore technique and grouped tumours as having high or low expression according to the median value.&#x2028; Cytoplasmic and nuclear NF-kB expression, either total or phosphorylated did not correlate with grade, size or lymph node involvement. However, nuclear phospho NF-kB expression was inversely associated with Ki67 proliferation index (p&lt;0.05). In addition an association between total nuclear NF-kB (p&lt;0.050) and total cytoplasmic NF-kB (p&lt;0.05) was observed with oestrogen (ER) and progesterone receptor (PR) status, total NF-kB expression was higher in ER and PR positive tumours (n=53) compared with ER negative and PR negative tumours (n=34). This association was also observed for nuclear phospho NF-kB (p&lt;0.001) but not cytoplasmic phospho NF-kB (p=0.292). In addition, ER positive and PR negative tumours (n=78) had reduced nuclear phospho NF-kB (p&lt;0.001) and cytoplasmic phospho NF-kB (p&lt;0.001) expression when compared with ER positive and PR positive tumours (n=53).&#x2028; These results suggest that reduced tumour expression of phospho NF-kb is associated with increased cell proliferation and PR negativity but not ER negativity in primary invasive breast cancer. The impact of such differential tumour expression of phospho NF-kB on outcome in breast cancer remains to be determined.&#x2028; 1. Cao Y, Karin M. NF-kappaB in mammary gland development and breast cancer.J Mammary Gland Biol Neoplasia. 2003;8:215-23.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4038.
Prognostic significance of GSTP1 and MGMT hypermethylation in invasive ductal breast carcinoma patients.
Authors: Sharma G , Mirza S , Parshad R , Gupta SD , Pandaya P , Ralhan R 
Published: December 2010

Abstract
Abstract #4053
Purpose: Methylation-mediated suppression of detoxification, DNA repair and tumor suppressor genes has been implicated in cancer development, by shifting cells from the normal cellular cycle to a state of high proliferation that favors tumor development and progression. The current study was designed to analyze the methylation status of these genes in sera of breast cancer patients and determine the correlation of promoter hypermethylation of these genes with disease prognosis and patient survival.&#x2028; Experimental design: To test the hypothesis that promoter methylation of GSTP1 and MGMT is associated with disease prognosis, the methylation status of these genes was analyzed in invasive ductal carcinoma tissues and corresponding sera of breast cancer patients and correlated with disease free survival of these patients.&#x2028; Results: Promoter methylation of GSTP1 and MGMT was observed in 25% and 38% of breast tumor tissues, respectively and in 23% and 35% of the corresponding sera of breast cancer patients. There was significant association between methylation of GSTP1 and advanced tumor stage. Patients harboring methylated GSTP1 were more likely to have disease progression and reduced overall survival compared with patients who did not have the methylated gene.&#x2028; Conclusion: GSTP1 methylation in tumor and sera may serve as a poor prognostic marker in patients with invasive ductal carcinoma.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4053.
p38 MAPK is altered transcriptionally, translationally, and post-translationally in inflammatory breast cancer – significance and implications.
Authors: Rosenthal DT , Dambro CR , Brenner JC , Wu Z , Merajver SD 
Published: December 2010

Abstract
Abstract #4061
Inflammatory breast cancer (IBC) is the most lethal form of breast cancer, with a 5-year survival rate below 45%. The disease progresses rapidly, and is typically identified as stage IIIb upon diagnosis. IBC is characterized by widespread invasion of the dermal lymphatics by tumor emboli, which results in lymphatic blockage. It is this blockage that leads to edema, erythema, and the subsequent “peau d'orange” appearance of the breast, and thus the misnomer “inflammatory” breast cancer.&#x2028; Little is known about the mechanisms of IBC metastasis, and as such the treatments available to patients are limited. Our lab identified RhoC GTPase as an oncogenic driver of the IBC phenotype, as overexpression of RhoC in normal human mammary epithelial cells (HME) leads to increased motility, invasion, and secretion of angiogenic factors. Ensuing studies from our lab revealed that p38 is involved in mediating IBC metastasis and invasion, as demonstrated by the effects of p38 inhibitors on RhoC-transfected HMEs. The aim of the current project was to determine the means by which IBC utilizes p38, and elucidate the contributions of the specific p38 isoforms to IBC metastasis and invasion.&#x2028; We demonstrate, for the first time, differences in the transcriptional, translational, and post-translational regulation of specific p38 MAPK isoforms in breast cancer, differences which delineate IBC from other invasive breast cancers, and invasive breast cancer from normal mammary epithelia. Furthermore, we show evidence that this upregulation is driven by RhoC overexpression. The contribution of each isoform to metastasis and invasion was then determined using isoform-specific expression vectors and RNA interference (RNAi). The results of this study will be useful in designing new drugs and therapies specific for IBC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4061.