bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do We Need Axillary Staging for All Breast Cancers? A Cohort Study from Sweden. The Natural Course of Small Breast Cancer.
Authors: Sveinsdottir H. 
Published: December 2010

Abstract
Introduction: Screening mammography, starting in the late eighties in Sweden, has improved the prognosis of breast cancer by detection of small breast cancer at an early stage.Thus, relatively fewer women have lymph node metastases at time of diagnosis. Data from a previous registry study from two Swedish regions showed that screening detected cancers &lt;10mm and Elston Grade 1-2 had a low rate of pN1 (7%). This prospective study investigates if axillary surgery safely can be omitted in such a predefined low risk group of breast cancer.Methods: A prospective cohort study was designed, including patients from 5 out of 6 regions in Sweden. From 1997-2002 1584 patients, with invasive breast cancer ≤10mm, Nottingham Histological Grade (NHG) I or II, were included in the cohort. These included patients did not have any axillary surgery at all. They were clinically followed for 5 years.As a complement to the study registry all patients being alive 10 years after study start received a questionnaire on recurrence, latest cancer control and adjuvant therapy in 2007-2009.Cause of death was collected from the Swedish Death Registry.Of the 1584 patients, 12 were excluded from the cohort due to re-evaluated size and grade.Results: Median age at inclusion was 61 years (31-87) and tumor size 8mm (range 1-10 mm). 94% underwent breast conserving surgery and 2/3 of them had postoperative radiotherapy to the breast, according to local Regional Guidelines.160 of the included patients have died, only 18 (1,1%) in breast cancer. 1412 pat received the questionnaire and 96% of them answered. Of patients alive, 109 patients (7,7%) were diagnosed with a recurrence or a contralateral breast cancer.Type of first recurrences were: 22 (1,5%) in ipsilateral lymph nodes; 9 (0.6%) as single event and 13 breast + axillary relapses), 55 in the breast only (3,9% of total) and 23 (1,6%) had contralateral breast cancer. 9 patients had distant metastases as first event.31 patients have so far been diagnosed with distant metastases, but 13 are still alive. 10 year over all survival is 88,7%, and breast cancer specific survival 97,4%.Conclusion: After a median follow-up time of 8,8 years only 0,6% had metastases in the axilla as first event and 0,7% showed relaps in breast together with the axilla. 6,6% of the patients were diagnosed with a recurrence of the breast cancer, 1,5% with contralateral breast cancer and 1,1% had died from breast cancer. Promising results with low rate of events in the axilla still give us a responsibility of meticulous control of this cohort for many years to provide us with important information on the natural course of early breast cancer and the significance of excluded axillary surgical staging for small tumours, even in the era of sentinel lymph node biopsy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1009.
SPIO Enhanced MR Imaging for the Detection of Metastases in Sentinel Nodes Localized by CT Lymphography in Patients with Breast Cancer.
Authors: Motomura K. , Ishitobi M. , Komoike Y. , Koyama H. , Inaji H. , Horinouchi T. , Nakanishi K. 
Published: December 2010

Abstract
Background: Ultrasonography, magnetic resonance (MR) imaging, and computed tomography (CT) may detect nodal metastases in patients with breast cancer, but there is not sufficient accuracy with the conventional methods. Recently, superparamagnetic nanoparticles-enhanced MR imaging has been reported to be a promising improvement for diagnostic imaging of lymph node metastases from various tumors. Moreover, sentinel nodes have been reported to be well-identified using CT lymphography in patients with breast cancer. This study evaluated MR imaging with superparamagnetic iron oxide (SPIO) enhancement for the detection of metastases in sentinel nodes localized by CT lymphography in patients with breast cancer, with histopathologic findings as the reference standard.Methods: This study included 102 patients with breast cancer with clinically negative nodes. Each contrast agent was injected intradermally into the skin overlying the breast tumor and in the subareolar region. Sentinel nodes were identified by CT lymphography, and SPIO-enhanced MR imaging of the axilla was performed to detect metastases in the sentinel nodes. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show a low signal intensity on MR imaging. Sentinel node biopsy was performed using a combination of dye and radiocolloid. Imaging results were correlated with histopathologic findings.Results: The mean number of sentinel nodes identified by CT lymphography was 1.1 (range 1–3). Twenty-one of 25 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Seventy of 77 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on imaging studies. The sensitivity, specificity, and overall accuracy of MR imaging for the diagnosis of sentinel node metastases were 84%, 91%, and 89%, respectively. In four of 10 patients with micrometastases, the metastases were not detected, but all 15 patients with macrometastases were successfully demonstrated. There were no adverse events associated with either CT or MR imaging.Conclusions: SPIO-enhanced MR imaging is a useful method of detecting metastases in sentinel nodes localized by CT lymphography in patients with breast cancer. Patients with clinically negative nodes may be spared sentinel node biopsy when the sentinel node is diagnosed as disease-free using SPIO-enhanced MR imaging.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1010.
Clinicopathological Factors and Nomograms Predicting Non Sentinel Lymph Nodes Metastases after Neoadjuvant Chemotherapy in Breast Cancer Patients.
Authors: Gimbergues P. , Abrial C. , Abrial C. , Durando X. , Durando X. , Le Bouëdec G. , Cachin F. , Cachin F. , Penault-Llorca F. , Mouret-Reynier M. , Mouret-Reynier M. , Kwiatkowski F. , Maublant J. , Maublant J. , Maublant J. , Tchirkov A. , Tchirkov A. , Dauplat J. , Chollet P. , Chollet P. , Chollet P. 
Published: December 2010

Abstract
Background : Studies have demonstrated the feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) in breast cancer. Some SLN-positive patients have low risk of non-sentinel lymph node (non-SLN) involvement. The aim of the present study performed on this group of SLN-positive patients after NAC was to determine clinicopathological factors associated with non-SLN involvement and to test scoring systems predicting the risk of additional nodal metastases currently available for SLN-positive patients not treated with NAC.Patients and methods : Patients with infiltrating breast carcinoma (n= 132) were studied prospectively. All patients received NAC. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. Lymphatic mapping was done using the isotope method. Fifty-one patients were SLN positive.Results : In univariate analysis, tumor size more than 26 mm (P= 0.016) and the size of SLN metastases more than 2 mm (P= 0.0055) were significantly correlated with the presence of non-SLN metastases. In multivariate analysis, SLN macrometastases conferred a 10.2-fold greater risk of non-SLN positivity than SLN micrometastases (P= 0.047, 95%-confidence interval, 1.15-90.2). The Memorial Sloan-Kettering Cancer Center nomogram was not reliably predictive for non-SLN metastases (AUC, area under the receiver operating characteristic curve, of 0.542), whereas the MD Anderson (AUC= 0.716) and Tenon scoring systems (AUC= 0.778) were validated.Conclusion: Our results suggest that clinicopathological factors predicting non-SLN involvement in SLN-positive patients with and without NAC are essentially the same. The risk of involvement may be assessed using existing nomograms, but additional large prospective studies are needed to determine their accuracy in patients after NAC.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1011.
Sentinel Lymph Node Navigation Surgery with Indocyanine Green Fluorescence in Early Breast Cancer.
Authors: Sugie T. , Kassim K. , Tsuji W. , Takeuchi M. , Yamashiro M. , Ueno T. , Toi M. 
Published: December 2010

Abstract
Background: Sentinel lymph node (SLN) biopsy is a minimally invasive and effective method for assessing axillary lymph node status in breast cancer. Currently dye techniques, radioisotope techniques or combined techniques are used for SLN detection and recently, near infrared fluorescence imaging has been applied clinically in a breast cancer patient to identify SLN. The concept of this technique is to detect the subcutaneous lymphatic flow from the areola toward the axilla in real time and identify SLN as florescence spot. Our aim in this study is evaluate the feasibility of SLNB by using the ICG technique and the effect of Body Mass Index (BMI) on the number of SLN identify. Methods: The study involved one hundred patients with clinically node negative early breast cancer who were assigned to SLNB, bilateral SLNB were performed on seven of them. A combination of indocyanine green as a fluorescence emitting source and patent blue dyes were injected in the periareolar area and a charge coupled device camera equipped with a cut filter was used, first to trace the subcutaneous lymphatic channels then to identify the florescence image of SLN after meticulous dissection. Both of them were seen in real time on a TV monitor. According to their florescence imaging and the blue color, the LNs were classified as SLN which is either double positive (ICG+/ Dye+) or single positive (ICG+/Dye- or ICG-/ Dye+) and para SLN which is double negative (ICG-/Dye -). Results: The subcutaneous lymphatic channels were detected precisely in all cases. The identification rate of SLN was 100%, (107/107) with a mean number of 3.7 nodes (rang-1 - 12), double positive nodes were found in 83.2% (89/107) with a mean number of 1.5 (range 0-6). The single positive SLNs, i.e. ICG+/ Dye- or ICG-/ Dye+ were found in (87/107) and (4/107) respectively. In twenty six cases (24.3%), the SLNs were involved and all of them were ICG positive. BMI is negatively correlated with number of double positive SLN identified (r= -0.19, P = .02). Conclusion: The ICG and patent blue dye technique gives high sensitivity and provides a comparable result to the dye and radioactive technique. Obesity may reduce the number of double positive SLNs identified.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1017.
Combining Genomic Profiling (70 Gene-Mammaprint) with Nodal Status Allows To Classify Patients with Primary Breast Cancer and Positive Lymph Nodes (1-9) into Very Distinct Prognostic Subgroups That Could Help Tailor Treatment Strategies.
Authors: Saghatchian M. , Mook S. , Pruneri G. , Viale G. , Glas A. , Eekhout I. , Delaloge S. , van 't Veer L. 
Published: December 2010

Abstract
OBJECTIVESThe axillary lymph node (LN) status is considered to be one of the most important factors for chemotherapy decision-making of operable breast cancer patients (pts). It is commonly agreed that combination therapies with taxane-containing regimens should be recommended for these pts, whereas high-dose regimens have failed to provide further improvement for pts clinically considered at high-risk.It has previously been shown that the 70-gene profile (MammaPrint®TM), which was developed in node-negative patients is excellent in predicting disease outcome in pts with 1-3 positive nodes and similarly in pts with 4-9 positive-nodes. Further analysis based on adjuvant treatment received and pooled analysis of the 2 LN positive series was performed in order to assess the prognostic added-value of genomic profiling in LN positive pts.METHODS Frozen tumor samples from breast cancer pts with positive LN coming from 2 hospitals were selected in consecutive series (1-3 LN, 4-9 LN; all female, diagnosed between 1984 and 1995, primary invasive breast carcinoma, unilateral T1, T2 or operable T3, mastectomy or breast-conserving therapy, no prior malignancies, fresh frozen tumor material available). Samples were evaluated by gene expression profiling for the 70-gene profile and were classified as genomic high risk (poor prognosis) or genomic low risk (good prognosis).RESULTS A total of 519 pts have been analyzed: 346 with 1-3 positive LN (PN1) and 173 with 4-9 positive LN (PN2). Among them, 212 (41%) had the 70-gene good prognosis-profile and 307 (59%) had the 70-gene poor prognosis-profile (strictly equal proportions among the 2 LN groups). Median follow-up was 10.3 years: distant metastases occurred in 141 patients (116 as first event) and 103 (20 %) died of their disease. Distance metastases as first event and breast cancer specific survival according to LN group (PN) and genomic profile (MP) are shown in Figures 1 and 2.CONCLUSION Our data show that the 70-gene profile is a strong prognostic marker of distant recurrence and breast specific death in breast cancer patients with positive LN. Combining nodal status (1-3 nodes vs. 4-9 nodes) and 70-gene profile (good vs. poor) allows stratifying patients among subgroups for whom tailored treatment strategies should be designed and assessed based on their very different outcome. Pts with elevated number of lymph nodes and high genomic risk have a very poor prognosis and might need to be considered for stronger treatment strategies.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 102.
China Validation Study of GeneSearchTM Breast Lymph Node Assay for the Diagnosis of Sentinel Lymph Nodes of Breast Cancer – CBCSG-001a Interim Results.
Authors: Wang Y. , Ouyang T. , Liu Y. , Wu J. , Yang X. , Su F. , Liao N. 
Published: December 2010

Abstract
Background: The use of sentinel lymph node (SLN) biopsy is becoming the standard of care in China. With the adoption of this technique there is an increasing need for rapid and accurate detection of metastases in the SLNs. Histological intra-operative techniques such as touch imprint and frozen section offer limited sensitivity, increasing the risk of intra-operatively missing relevant SLN metastases (&gt;0.2 mm). Post-operative histology (H&E) also risks missing metastases due to tissue sampling limitations and being partially dependent on pathologist expertise. A real-time RT-PCR assay, GeneSearchÔ Breast Lymph Node (BLN) Assay, may offer a standardized intra-operative way to evaluate larger portions of the SLN. CBCSG-001a is a prospective multicenter trial to validate the GeneSearchÔ BLN Assay in China.Methods: Started from February 2009, CBCSG-001a is being conducted at 6 centers with a total enrollment of 540 cases by the end of June 2009. SLNs are cut into alternating ∼2mm sections. One half of the sections are sampled for H&E. The other half is fully tested with the BLN assay. The assay detects the presence of cytokeratin-19 and mammaglobin to assess if metastases are in SLNS. Predetermined cutoffs are calibrated so only metastases &gt;0.2 mm are detected. Each assay run has internal and external controls to confirm a valid result.About 40% cases would receive axillary lymph node dissection (ALND) in spite of the status of SLN in 3 of the 6 centers. Intraoperative frozen section for SLN diagnosis was conducted in 4 of the 6 centers, and intraoperative touch imprint cytological diagnosis for all sections was conduced in 2 of the 6 centers.Results: Interim results are based on 20% (114/540) of the planned breast cancer patients for the study. Current histology positive rate is 30%. The BLN assay shows high performance as compared to H&E. The results are also very similar to those seen in the larger US clinical validation trial.Discussion: Interim results indicate that the BLN assay has high performance as compared to H&E, and allows same surgery ALND avoiding the need to wait for a second surgery. In addition the performance is equivalent to the results seen in the larger US clinical validation trial, indicating the assay performance is fairly robust. So there is clinical potential of using the assay for performance similar to H&E with the advantage of being an intra-operative, objective and standardized test that examines a larger portion on the nodal tissue. The final results of 550 cases will be updated at the SABCS.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1023.
Limited Clinical Utility of Prognostic Gene Expression Profiles in Grade 3 Node-Negative Early Stage Breast Cancer.
Authors: Bedard P. , Ignatiadis M. , Haibe-Kains B. , Haibe-Kains B. , Loi S. , Criscitiello C. , Desmedt C. , Bontempi G. , Piccart M. , Piccart M. , Sotiriou C. , Sotiriou C. 
Published: December 2010

Abstract
Background: There are a variety of commercially available prognostic gene expression profiles (GEPs) for early stage breast cancer. These have been shown to be highly concordant in their risk classification, as their prognostic performance is largely driven by an improved quantification of cellular proliferation in the ER+/HER2- (luminal) subtype. We hypothesized that the clinical utility of prognostic GEPs would be limited to the subset of tumors with an indeterminate assessment of proliferation by histological grading (grade 2).Methods: We computed five gene-expression signatures – genomic grade index (GGI), 70-gene signature (GENE70), 76-gene signature (GENE76), 21-gene recurrence score, and wound response signature – in 999 lymph node negative, untreated breast tumors (median follow-up of 7.8 years) from six publicly available datasets. We compared their performance against traditional clinicopathological risk classification using Adjuvant!Online (AOL) for each histological grading category.Results: All five GEPs demonstrated superior prognostication of 10-year distant metastasis free survival (DMFS) in grade 1 (range of area under the ROC curves (AUC)=0.63-0.75) and grade 2 (AUC=0.64-0.71) tumors than in grade 3 (AUC=0.48-0.53) tumors. For the GGI, GENE70, and GENE76 profiles, discordant risk classification with AOL was more frequent in grade 2 (53%) than grade 1 (38%) and grade 3 (26%) tumors (p&lt;.001). In the event of discordant risk classification, GEP identified a low risk subgroup that might be spared chemotherapy in grade 2 (10-yr DFMS: 80% vs 66% (GGI); 81% vs 65% (GENE70); 80% vs 67% (GENE76)) and grade 1 (10-yr DFMS: 92% vs 69% (GGI); 84% vs 79% (GENE70); and 87% vs 70% (GENE76)) but not grade 3 (10-yr DFMS: 67% vs 47% (GGI); 75% vs 47% (GENE70); and 71% vs 52% (GENE76)). Even within the subset of all small (T&lt;2cm), ER-positive, node-negative grade 3 tumors, low genomic risk patients did not experience a sufficiently favorable long-term outcome (10-yr DMFS: 60% (GGI), 69% (GENE70) and 64% (GENE76)) to justify the omission of adjuvant chemotherapy.Conclusion: There is limited clinical utility of prognostic GEPs in grade 3 early breast cancer. Histological grading should guide decision-making for assessment of genomic risk.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 103.
Comparison of Prognostic Signatures in Node-Negative Tamoxifen-Treated Breast Cancer Patients.
Authors: Müller V. , Schmidt M. , Rody A. , Milde-Langosch K. , Kaufmann M. , Kölbl H. , Jänicke F. , Weber K. , Gehrmann M. 
Published: December 2010

Abstract
Background: A number of molecular signatures have been published to aid breast cancer prognosis and therapy response prediction. A 76-gene signature has been developed in a node-negative patient cohort that did not receive systemic therapy.1 Another prognostic 97-gene signature measures predominantly proliferation-associated genes.2 Finally, a 21-gene signature has been developed for node-negative and estrogen receptor–positive breast cancer patients treated with tamoxifen in the adjuvant setting.3 Here we compare the prognostic performance of all three published algorithms in a cohort of 189 node-negative breast cancer patients treated with tamoxifen.Materials and Methods: Fresh-frozen tumors from node-negative patients were profiled on HG-U133a arrays. In addition, HG-U133a datasets with clinical annotation were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/). All patients received tamoxifen only as adjuvant treatment after surgery. We determined the molecular subclass on the basis of ESR1 and ERBB2 mRNA expression; only ESR1-positive and ERBB2-negative tumors were considered for further analysis, leaving 141 in-house and 48 public datasets. After mapping of the gene signatures to the HG-U133a platform, we performed Cox regression and ROC curve analysis with distant metastasis as endpoint.Results: Cox regression analysis yielded a significant outcome association for all three gene signatures (76-gene signature: P = 0.0018; 97-gene signature: P = 0.0294; 21-gene signature: P = 0.0025) in the whole ESR1+/ERBB2– cohort. However, the 97-gene signature did not yield a significant result by ROC analysis for distant metastasis at 5 years (76-gene signature: AUC = 0.645, CI = 0.505–0.785; 97-gene signature: AUC = 0.608, CI = 0.462–0.754; 21-gene signature: AUC = 0.744, CI = 0.633–0.854). In addition, when the analysis was restricted to grade 2 tumors (n = 114), only the 21-gene signature remained prognostic by Cox regression (76-gene signature: P = 0.2405; 97-gene signature: P = 0.9001; 21-gene signature: P = 0.047) as well as by ROC curve analysis at 5 years (76-gene signature: AUC = 0.575, CI = 0.398–0.751; 97-gene signature: AUC = 0.532, CI = 0.347–0.717; 21-gene signature: AUC = 0.699, CI = 0.549–0.849).Discussion: While all three gene signatures reveal a significant outcome association in our whole patient cohort by Cox regression analysis, only the 21-gene signature remains significant in a subset analysis of grade 2 tumors. Since this group is clinically particularly challenging, further comparison between prognostic gene signatures in homogeneously treated patient cohorts is needed.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 104.