bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-Dose Tamoxifen for the Treatment of Breast Ductal Intraepithelial Neoplasia: Results of a Large Observational Study.
Authors: Guerrieri-Gonzaga A. , Botteri E. , Lazzeroni M. , Lazzeroni M. , Bonanni B. , Rotmensz N. , Goldhirsch A. , Varricchio C. , Serrano D. , Cazzaniga M. , Luini A. , Viale G. , Viale G. , Mora S. , Bollani G. , Albertazzi E. , Decensi A. , Decensi A. 
Published: December 2010

Abstract
Background: The cost-benefit ratio of tamoxifen for breast ductal intraepithelial neoplasia (DIN) is unclear. Since low-dose tamoxifen showed a favorable safety profile and modulation of breast cancer biomarkers in phase II trials, we analyzed a large mono-institutional cohort of women with DIN treated with low-dose tamoxifen or no systemic treatment.Material and Methods: A total of 309 patients with ER positive DIN received either tamoxifen 5 mg/day or 20 mg/week, as part of clinical trials or institutional guidelines and were compared with 371 patients who received no systemic treatment after surgery with or without radiotherapy due to personal preference, allocation to placebo or contraindication to tamoxifen.Results: The 5-year cumulative incidence of recurrence was 14.5% (95% CI, 11.9-17.5), with a negative trend according to age. Women with ER/PgR &gt;50% DIN who were untreated had a higher incidence of breast events than women on tamoxifen (HR 1.76; 95% CI, 1.00-3.12) or women with ER/PgR&lt;50% DIN (HR 1.72; 95% CI, 1.14-2.58). Among untreated patients with ER&gt;50% DIN, recurrence was higher in PgR ≥50% DIN than in PgR &lt;50% DIN, whereas it was similar among low PgR (&lt;50%) DIN against which tamoxifen had no effect. No difference in endometrial cancer incidence was noted.Discussion: High ER and especially high PgR expression is a significant adverse prognostic indicator of DIN against which low-dose tamoxifen appears to be a safe and active treatment. Conversely, women with low expression ER or PgR DIN do not seem to benefit from tamoxifen. A definitive clinical trial is warranted.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2113.
Long-Term Survival of Breast Ductal Carcinoma In Situ in Women with Different Gene-Expression Types.
Authors: Zhou W. , Johansson C. , Jirström K. , Olorunsola A. , Garmo H. , Wärnberg F. 
Published: December 2010

Abstract
Background: Basal-like invasive breast cancer has been shown to be associated with a worse prognosis. However, we do not know if basal-like ductal carcinoma in situ (DCIS) relates to a worse prognosis. The purpose of this study was to relate the DCIS basal-like subgroup, evaluated by immunohistochemistry (IHC), with prognosis.Material and Methods: Women diagnosed with a primary DCIS 1986-2004 in Uppsala and Västerås, Sweden were recruited (n=458). TMA blocks were constructed and IHC for Estrogen receptor (ER), Her2, epidermal growth factor receptor (EGFR/Her1) and cytokeratin 5/6 (CK 5/6) was employed to evaluate the gene-expression subgroups. Subtype definitions were as follows: luminal A (ER+ and HER2–), luminal B (ER+ and HER2+), basal-like (ER–, HER2–, CK 5/6+ and/or EGFR+), HER2+ (ER– and HER2+), and others (negative for all markers or data missing).Results: We followed 458 patients for local recurrence, general disease and all-causes mortality. Median follow-up was 122 months. Of the 458 primary DCIS breast cancers, 224 (48.9%) were luminal A subtype, 63 (13.8%) were luminal B, 80 (17.5%) were Her2+, 29 (6.3%) basal-like and 62 (13.5%) unclassified. Local recurrence and general disease rates were similar when comparing basal-like group with each of the other four groups. Compared with the most common luminal A tumors, basal-like tumors were related with poorer survival (hazard ratio 2.56, 95% confidence interval 1.05 – 6.22). When compared with luminal B, Her2+ and unclassified group, basal-like tumors were related with non-significant poorer survival, with a HR (95% CI) of 1.37 (0.52 – 3.64), 1.80 (0.69 – 4.72) and 2.61 (0.61 – 11.2), respectively. We also compared basal-like group with the rest combined as one non-basal-like group. Local recurrence and general disease rates were similar in these two groups. Women with basal-like DCIS had higher mortality than women in the non-basal-like group (HR 2.26, 95% CI 1.00 - 5.10).Conclusion: Basal-like DCIS women may have poorer overall survival, particularly in comparison with luminal A DCIS.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2114.
Is Accelerated Partial Breast Irradiation Appropriate Adjuvant Therapy for Patients with Ductal Carcinoma In-Situ?
Authors: Careaga E. , Hughes J. , Allen L. , Carella R. , Frazier T. 
Published: December 2010

Abstract
Introduction: Accelerated partial breast irradiation (APBI) using high-dose rate (HDR) balloon catheter breast brachytherapy following wide segmental resection of the breast has been shown to be equivalent to whole breast irradiation (WB-XRT) in the treatment of stage-I breast carcinoma. Because the majority of all breast cancers recur in the same quadrant as the original tumor, the advantages of this treatment compared with WB-XRT include concentration of radiation in the area where cancer is most likely to recur, shorter treatment duration, and greater patient acceptance. This study examined the rate of local/regional recurrence in patients diagnosed with stage-0 breast cancer, specifically ductal carcinoma in-situ (DCIS), following wide segmental resection of the breast and treatment with APBI using HDR balloon catheter breast brachytherapy.Methods: An IRB-approved, single-institution, retrospective chart review was conducted identifying 40 patients diagnosed with stage-0 breast cancer between March, 2004 and April, 2008 who were treated with wide segmental resection of the breast followed by APBI using HDR MammoSite™ balloon catheter breast brachytherapy. Outcome measures included rates of same-quadrant recurrence, ipsilateral second-primary occurrence, and regional recurrence.Results: Patient age ranged from 44 to 89 years (median = 69 years) with a median follow-up of 40 months (range: 16 to 60 months). All 40 patients had DCIS. One patient of 40 (2.5%) had DCIS with an additional focus of lobular carcinoma in-situ. 29 of 40 patients (72.5%) were estrogen receptor (ER) positive. Of these 29 patients, 17 were also progesterone receptor (PR) positive. One patient (2.5%) at 38 months experienced a local recurrence of DCIS with micro-invasion and a synchronous focus of invasive ductal carcinoma in a separate quadrant. This was subsequently treated with total mastectomy, sentinel lymph node mapping, and axillary lymph node dissection. No other patients experienced local-regional recurrence or ipsilateral primary breast cancer occurrence.Conclusion: Patients with DCIS can be effectively treated with APBI/HDR balloon catheter breast brachytherapy following wide segmental breast resection. The rate of local-regional recurrence was 2.5% at a median follow-up time of 40 months. This is consistent with that of patients with DCIS treated with wide segmental breast resection followed by WB-XRT. Long-term follow-up will be required to assure these rates remain favorable.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2116.
The Expression of Insulin-Like Growth Factor-1 Receptor (IGF-1R) in Early Breast Cancer.
Authors: Spears M. , Cunningham C. , Thomas J. , Kerr G. , Jack W. , Campbell F. , McKay L. , Kunkler I. , Cameron D. , Chetty U. , Bartlett J. 
Published: December 2010

Abstract
Background: The insulin-like growth factor-1 receptor (IGF-1R) is expressed in normal breast epithelial cells and breast carcinomas. A number of studies have examined the over-expression of IGF-1R in breast cancer with the range of between 39% to 93%. However, many of these studies were carried out using ELISAs, radioimmunoassay with small patient cohorts. Phosphorylation of IGF-1R results in the activation of the MAPK and PI3K/Akt pathway. Activation of the PI3K/Akt pathway under the influence of IGF-1R plays an important role in maintaining the proliferation of breast cancer cells that are resistant to gefitnib, trastuzumab or chemoradiotherapy in vitro and in vivo. In the present study, we examined the expression of IGF-1R in early breast cancer and investigated the clinicopathological implications using immunohistochemistry and FISH.Methods: TMAs from a consecutive series (1981-98) of 1,812 women managed by wide local excision and postoperative radiotherapy (45Gy in 20-25 fractions) were collected following appropriate ethical review. Of 1686 cases stained, 198 received no adjuvant hormonal or chemotherapy, 1106 received tamoxifen only as adjuvant therapy and 144 received a combination of hormonal and chemotherapy. Median age at diagnosis was 56, 72% were post-menopausal, 23.9% node positive, median size was 1.5 cm. Samples were stained, using triplicate 0.6mm2 TMA cores for IGF-1R.Results: FISH for IGF1R gene amplification was successful in 343/408 cases (84%). Only 7 cases of IGF1R amplification were observed (2%). IGF1R expression was successfully evaluated in 1597 of 1686 (94.7%) cases. High levels of IGF-1R expression was weakly associated with tumour ER-a (correlation coefficient, 0.108; p=2.2 x 10-5) and PgR levels (correlation coefficient 0.162; p=1.86x10-10) and inversely correlated with EGFR expression (correlation coefficient -0.189; p=6.33x10-6). No association was noted between IGF1R expression and other molecular or clinical markers, such as tumour size. There was a trend for over-expression of IGF-1R to link with increased distant relapse free survival, particularly in ER positive breast cancers. This trend is time dependent, such that no difference in outcome is observed at 15 years.Conclusions: We have demonstrated in a large cohort of patients that IGF-1R gene amplification is a rare event, and over-expression is weakly associated with good prognostic features (ERa and PgR, lack of EGFR and better outcome).
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2128.
Stromal Caveolin-1 Levels Predict Early Ductal Carcinoma In Situ Progression to Invasive Breast Carcinoma.
Authors: Witkiewicz A. , Dasgupta A. , Schwartz G. , Nguyen K. , Rui H. , Lisanti M. 
Published: December 2010

Abstract
With the increase use of screening mammography the incidence of ductal carcinoma in situ (DCIS) increased and DCIS currently accounts for 20-30% of newly diagnosed breast cancers.The current classification for DCIS based on nuclear grade, architectural differentiation and presence of necrosis, does not adequately predict the likelihood of recurrence after breast conservingtherapy. Therefore, there is a critical need to identify novel predictors of DCIS progression and potential targets for therapy. Recently, we showed that an absence of stromal caveolin-1 (Cav-1)expression in invasive breast cancers is a powerful single independent predictor of early disease recurrence and metastasis. The aim of this study was to evaluate the stromal expression of Cav-1 in a cohort of DCIS patients treated with wide-excision and close follow-up, but without any form of chemo- or radiotherapy.Material and MethodsSeventy eighty DCIS cases were included in the study. Cav-1 expression in the tumor stroma was assessed by employing a standard immunoperoxidase method with monoclonal ani-Cav-1 antibody (BD Biosciences, San Jose, CA; 1:50 dilution).The staining was scored semi-quantitatively as negative (0; no staining), weak (1; either diffuse weak staining or strong staining in less than 30% of stromal cells) and strong (2; defined as strong staining of 30% of stromal cells).Statistical analysis was performed using the Fisher exact test or the Kruskal-Wallis test.ResultsThe overall recurrence rate was twenty-eight percent (50% recurred as DCIS, and the other 50% recurred with progression to invasive breast cancer). Nearly seventy percent of DCIS patients with any type of recurrence had reduced levels of stromal Cav-1 (score = 1 or 0). Eighty nine percent of DCIS patients that underwent recurrence with progression to invasive breast cancer had reduced or absent levels of stromal Cav-1. Conversely, ninety-seven percent of DCIS patients with high levels of stromal Cav-1 (score = 2) did not show any invasive recurrence over the duration of follow-up (4-208 months).Our results indicate that an absence of stromal Cav-1 is a novel biomarker that predicts early DCIS progression to invasive breast carcinoma.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2136.
Delineating the Secretome of Eleven Breast Cell Lines in the Quest for Novel Breast Cancer Biomarkers.
Authors: Pavlou M. , Pavlou M. , Diamandis E. , Diamandis E. , Diamandis E. 
Published: December 2010

Abstract
Background: Close to 200,000 new cases of breast cancer are estimated in United States for 2009, rendering breast cancer the most frequently diagnosed cancer in women. Patients diagnosed with early stage breast cancer have significantly improved survival rates compared to late stage patients, underlining the need for identification of biomarkers for early detection. In this study the secretome of 11 breast cell lines was analyzed by tandem mass spectrometry to identify novel breast cancer biomarkers.Materials and Methods: To reflect disease heterogeneity, three cell lines for each breast cancer type (estrogen/ progesterone receptor positive, triple negative, HER2/neu amplified) along with two near-normal cell lines were selected (HCC-1428, BT483, MCF-7, MDA-MB-231, HCC-1143, HCC-38, SK-BR-3, HCC-202, UACC-812). The conditioned media were lyophilized to dryness and the proteins were denaturated, reduced and trypsin digested. The peptides were separated by strong cation chromatography and the resulted fractions were analyzed in a linear ion-trap coupled to an orbitrap mass analyser. All samples were run in duplicate and spectra were searched with Mascot and X!Tandem engines. Scaffold software was used to cross-validate Mascot and X!Tandem results.Results and Discussion: Over 800 unique proteins were identified in the conditioned media of each cell line, resulting in more than 4,000 proteins from the eleven breast cell lines. More than 40% of the proteins were identified with at least 2 unique peptides and the reproducibility between replicates of the same cell line was approximately 70-80%. Using an in-house developed program, we compared the proteomes of all the cell lines to distinguish unique and common proteins and we determined the cellular localization and the biological function for each protein. Then, we focused on extracellular and plasma membrane proteins, which constitute approximately 30% of total proteins, since secreted or shed proteins are more likely to enter the circulation and serve as potential biomarkers. This list of candidates was compared to the existing nipple aspirate fluid proteome to select proteins that have been also detected in breast microenvironment. These proteins were further analyzed based on Unigene database and appropriate literature to select the final list of 10 candidates for validation by immunoassays.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2137.
Molecular Biomarkers of Columnar Cell Lesions Identified by Proteomic Approaches.
Authors: Pape-Zambito D. , Kistler J. , Chen X. , Li X. , Chen Y. , Cai K. , Wu H. , Huang M. , Yeung A. , Patchefsky A. , Daly M. , Godwin A. 
Published: December 2010

Abstract
The widespread increase in the use of screening mammography has led to a significant rise in the detection and diagnosis of benign breast disease (BBD), which encompasses a wide variety of non-cancerous changes including columnar cell lesions (CCL). Epidemiologic studies provide evidence for a relationship between BBD and subsequent risk of developing breast cancer. Observational studies have reported CCL are found adjacent to areas of tubular carcinoma and ductal and lobular carcinomas in situ and recently published molecular data state that genetic abnormalities frequently found in low grade ductal carcinoma in situ are also found in CCL. All these data support the hypothesis that CCL are the earliest morphologically distinguishable precursor lesions to low grade ductal carcinoma in situ and invasive carcinoma. However, BBD is heterogeneous and there is limited understanding of the biological importance associated with the spectrum of lesions. The lack of accurate molecular-based risk categories, therefore, hinders the ability of assigning prognostic significance to benign biopsy findings. The purpose of our study was to identify putative molecular markers of cancer progression from epithelial cells of BBD lesions. Regions of ductal hyperplasia (DH) and normal breast epithelium were isolated from mastectomy specimens using laser capture microdissection and extracted proteins were analyzed through proteomic approaches. Of the 1,500 total protein spots resolved by 2-dimensional electrophoresis, 98 were differentially expressed between DH and normal breast epithelial proteomes. Twenty-two proteins or related isoforms were identified using mass spectrometry. Two proteins of particular interest, NAD(P)H: quinone oxidoreductase 1 (NQO1) and galectin-3, were further investigated by immunohistochemistry (IHC) on cases diagnosed with BBD lesions. NQO1 was expressed sporadically in overtly normal epithelial cells lining breast ducts, but was overexpressed in BBD and tumor tissues. Notably, we found that a subpopulation of DH tissues with CCL stained positively for NQO1 and negatively for galectin-3. This finding has significance because CCL can only be diagnosed morphologically and the presence of CCL in biopsy specimens may indicate a precancerous lesion. However, sectioning artifacts associated with core biopsies can hinder morphological diagnosis of CCL, thus a means to additionally identify these lesions using IHC has tremendous value. Together, immunohistochemical staining of NQO1 and galectin-3 may prove to be clinically relevant in the identification of CCL in biopsy samples.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2142.
Albumin-Binding and Angiogenic Domains of SPARC Located at Its C-Terminus.
Authors: Knauer D. , Hwang L. , Lowe C. , Hwang J. , Norng M. , Trieu V. , Desai N. 
Published: December 2010

Abstract
Background: SPARC (Secreted Protein Acidic and Rich in Cysteine) is an albumin-binding glycoprotein overexpressed in breast cancer and is associated with poor prognosis and shorter overall survival. We have previously shown that SPARC expression appeared to correlate with response to nanoparticle albumin-bound (nab) paclitaxel (Abraxane) in head-and-neck and pancreatic-cancer patients. To further define the role of SPARC, recombinant-human SPARC (rhSPARC) was characterized to identify its albumin-binding and angiogenic domain.Materials and methods: The albumin-binding site on SPARC was defined by testing the binding of Alexa 488-labeled BSA to immobilized rhSPARC in a solid-phase-binding assay and in a competitive-binding assay in presence of increasing concentration of various SPARC-derived peptides. The angiogenic activity of rhSPARC was evaluated using a HUVEC tube-formation assay.Results: The SPARC albumin-binding assay revealed a pattern of saturable and specific binding with an estimated Kd of 700 µM very near the known plasma concentration of albumin (600 µM). Competitive binding with Cathepsin K-digested SPARC and SPARC-derived peptides defined the albumin-binding domain to be amino acids 209-223 in the C-terminal region. In the HUVEC tube-formation assay, rhSPARC was pro-angiogenic at 10 µg/ml and anti-angiogenic at 100 µg/ml. The angiogenic domain of SPARC was located to the C-terminal of SPARC.Discussion: The albumin-binding domain of SPARC was located to residues aa209-223, supporting its role as a target for nab-technology-based drug delivery. We confirmed that SPARC can promote angiogenesis at physiological concentrations, contributing to the role of SPARC in a more aggressive tumor phenotype. The angiogenic domain of SPARC is located within a 54-aa sequence of its C-terminus. SPARC could be a potential therapeutic target and a biomarker for predicting response to nab-paclitaxel.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2144.
Anastrozole Reduces Progesterone and Proliferation Index in Short Term Hormone Therapy. A Prospective Placebo Double Blind Study.
Authors: Mattar A. , Logullo A. , Facina G. , Nonogaki S. , Soares F. , Gebrim L. 
Published: December 2010

Abstract
Background: Identification of new biomarkers with potential predictive and prognostic role has contributed unequivocally to breast cancer treatment. Although traditionally endocrine therapy is based on Hormonal receptors status (estrogen - ER and progesterone- PR), some patients become hormone resistant. In order to identify a possible profile associated to hormonal resistance, some biomarkers have been assessed after short period primary hormone therapy (HT).Objectives: To compare the expression of Ki-67, Bcl2, Bax, Bak, ER and e PR in postmenopausal women with ER positive invasive ductal carcinomas (IDC), prior and after tamoxifen and anastrozole in neoadjuvant treatment.Methods: Fifty-eight patients with palpable ER-positive IDC (stage II and III) were double-blind randomized in a prospective placebo controlled study with three neoadjuvant HT groups for twenty-six days prior to surgical treatment: Anastrozole 1mg/day (n= 18), Placebo (n=25) and Tamoxifen 20mg/day (n= 15). Pre and post HT samples were disposed in tissue micro array blocks and submitted to immunohistochemical essay. Biomarkers status (Ki-67, Bcl2, Bax, Bak, ER and e PR) were obtained comparing each immunohistochemical evaluation of pre and post-surgery samples using semi-quantitative Allred's method. Statistical analysis were performed using the GEE (General Estimation Equations) and Anova tests with significant p ≤ 0,05.Results: ER and PR status did not change significantly in placebo group (96% -96% and 76-72%) and KI-67 index variation was 40 to 52% (p&gt;0,05), as expected. In Tamoxifen group, ER status was also stable during treatment (100-100%). However, in anastrozole group, ER status -originally 100% - lowered to 89%,(p&gt;0,05) and also PR expression rates lowered significantly from 56% to 28% in post treatment (p=0,0007). Anastrozole group also showed a significant reduction in KI-67 status from 78% in the pre-treatment KI-67 to 39% in post treatment samples (p=0,0079). Tamoxifen group showed a slight increase of PR expression from 73% to 93% along a non-statistical significant variation of KI-67 status 67% pre-treatment to 47% post-treatment. The other biomarkers (RE, Bak, Bax, Bcl-2 )did not show any variation in the three groups evaluated.Conclusions: a significant reduction of PR and ki-67 status was associated to Anastrozol treatment (26 days, 1mg/day). Short primary HT was not associated to any variation in apoptosis-related proteins (Bak, Bax, Bcl-2) regardless the drug used.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2145.