P20 Assessment of breast cancer tumor size depends onmethod, histopathology and tumor size itself

P20 Assessment of breast cancer tumor size depends onmethod, histopathology and tumor size itself

Thursday, 27 January 2005 IP~ Accessory breast carcinoma: a case report and review of the literature H.S. Lee 1 , S.H. Jung ~, B.Y. Koo ~. ~ Chonbuk...

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Thursday, 27 January 2005 IP~

Accessory breast carcinoma: a case report and review of the literature

H.S. Lee 1 , S.H. Jung ~, B.Y. Koo ~. ~ Chonbuk National University Medical

School, Department of Surgery, Jeonju, South Korea Ectopic breast usually develops along the mammary ridges, and the incidence has been reported up to 6%. Occurrence of primary breast cancer in ectopic breast tissue is rare. We here report a case of 59-year-old woman with primary breast cancer in accessory breast in the left axilla, and review the literature on ectopic breast carcimoma.

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Comparison between the 5th and 6th American Joint Committee on Cancer (AJCC) staging system in 1,275 breast cancer patients

S.H. Kang 1, K.H. Jung 1, S.J. Lee ~, K.B. Kwun 1. ~ College of Medicine,

Yeungnam University, General Surgery, Daegu, South Korea

Poster Session L Diagnosis~Screening~Pathology

S 19

Results: We tested both in vitro transcription and single primer amplification and showed that linear PCR was the most reliable protocol on our support. This protocol consistently produces unbiased amplification of mRNA compared to the standard non-amplified protocol (R=86%). Importantly, sensitivity of colorimetric compared to radioactive detection is very good (R*=85%) over a dynamic range of 3 logs. High intra- and inter-operator reproducibility (n=78) on cell line RNA was demonstrated (CV = 15%). Automated quantification with ProfileSoftware T M Cancer was strongly correlated to commercial quantification software and does not require manual grid positioning. The software checks for data quality, and performs appropriate normalization procedures. Each patient expression profile is then compared to the reference database and the tumor characteristics predicted using GES. Results are stored in a database and included in a pathology report which contains all information required by FDA Guidelines. Conclusions: This study describes the development of a decentralized test utilizing GEP technology designed for use in a clinical setting, and may contribute to more efficient tumor characterization and optimal clinical management of breast cancer.

Purpose: Since the publication of the 5th edition of the AJCC cancer staging manual in 1997 (old stage), significant developments have occurred in the field of breast cancer diagnosis and management; therefore, it was revised at 2002 (new stage). There are few reports comparing the changes in prognosis in relation to the changes in the staging system. The aims of this study were to evaluate the changes in patient distribution and prognosis according to the changes in the staging system and to elucidate the efficacy of new staging system. Methods: The records of 1,275 patients who underwent an operation for breast cancer at Yeung-Nam University Hospital, Daegu, Korea between 1987 and 2003 were reviewed. The pathological stage was assigned retrospectively according to the 5th and the 6th AJCC staging criteria. The patient distributions by stage, nodal status, 5-year relapse free survival (RFSR) and overall survival rates (OSR) were retrospectively compared. Results: Five hundred and five of 616 stage II patients according to the 1997 classification system were also stage II according to the 6th AJCC staging system. The number of patients with stages IIA and liB decreased from 370 and 246 (old stage) to 342 and 165 (new stage), respectively. Conversely, the number of patients with stage III increased from 158 (old stage) to 271 (new stage). The five-year RFSR for patients with stage I, IIA, liB, and IliA were 94.2, 87.1, 74.3, and 48.8% according to the old stage (p<0.0001), and 95.2, 87.8, 81.7, and 66.8%, respectively, according to the new stage (p<0.0001). The five-year OSR for patients with stage I, IIA, liB, and IliA were 98.7, 94.3, 86.1, and 63.5% according to the old stage (p<0.0001), and 98.7, 95.7, 96.5, and 72.9%, respectively, according to the new stage (p<0.0001). The RFSR and OSR for stage IIIC were 42.0 and 59.5%, respectively. There was significant difference in the five-year OSR for stages liB and IliA (p=0.0308 and p=0.0132, respectively). Conclusions: in our study, the 6th AJCC staging system shifted poorer prognostic cohort of each stage toward a higher stage compared to the 1997 version. Therefore, the survival rate for any one stage assigned by 2002 staging system was also improved. In conclusion, it is imperative that careful attention is devoted to this effect so that accurate conclusions regarding the efficacy of new treatment can be drawn.

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Development of the Breast Cancer ProfileChipTM, a new diagnostic device dedicated to breast cancer

N. Borie 1 , S. Deraco 1 , J. Cabrera 1 , A. Lamy de la Chapelle 1, O. Biglia 1, E Hermitte 1 , S. Debono 1 , E Bertucci 2, D. Birnbaum 2 , A. Koki 1.

11PSOGEN, R&D, Marseille, France; 2 Institut Paoli Calmettes, Oncology, Marseille, France

Background: Although there is increasing evidence on the importance of microarray technology for the characterization of tumors, the transfer from research tool to diagnostic tool has yet to be achieved. The complex analyses of data generated by microarrays are one of the most important issues. Here, we present the development of a complete diagnostic device for tumor characterization providing both molecular reagents and bioinformatics tools for automated data interpretation. Methods: Gene expression signatures (GES) were previously identified based on large-scale gene expression profiling (GEP) on nylon-based chips containing 10K genes. Selected genes were transferred to a dedicated biochip containing 900 genes. A protocol for amplification and colorimetric detection was developed and optimized for use in clinical laboratories. Dedicated software (ProfileSoftware T M Cancer) was also designed for automated biochip quantification and data interpretation. ProfileSoftware T M Cancer has been developed using FDA and IEEE guidelines on software development and validation. Validation of sample processing was performed by comparison between amplification and standard RT labeling and radioactive vs- colorimetric detection.

~P--~ Histological diagnosis of lesions of the female breast within 1 hour from core-cut-biopsies - a prospective study to compare breast imaging, rapid embedding and postoperative histological diagnosis K. Rensing 1, R. Laarveld 1, G. Omar 1 , D. Rensing 1, R. Lelle 1.

i Universitaetsklinikum Muenster, Klinik und Poliklinik for Frauenheilkunde und Geburtshilfe, Muenster, Germany

Introduction: Nowadays the preoperative histological diagnosis of breast lesions is an important and critical condition for the management of further therapy. Rapid embedding (RE) of core-cut-biopsies seems to be a promising tool for fast diagnosis. Because of the small amount of tissue this innovative method has to be evaluated in comparison to preinvasive breast imaging methods, i.e. mammography (MGr) and ultrasound (US), as well as to final postoperative histological (FH) results. Patients and methods: From january 2002 to december 2003 187 corecut biopsies were performed. Using the BIRADS and BIRADS-US system we compared imaging results to histological (rapid embedding, final histology)and cytological analysis (Thin-prep). In 182 cases ultrasound and RE and in 105 cases mammography and RE could be compared. 57 operative procedures were done afterwards, making a comparison to standardized histological analysis possible. Results: In MGr and RE 34 cases were classified as benign, 35 cases as malignant. Different results occurred in 36 cases: 25 as benign classified MGr (BIRADS I1-111)were diagnosed as breast cancers in RE and confirmed in FH - 11-times BIRADS IV/V in MGr were not diagnosed as malignant in RE. US and RE showed the same diagnosis in 82 of 182 investigations, i.e. 41 benign and 41 malignant diagnoses. Differences occurred in 34 patients - 12 BIRADS-US II/111were malignant histologically in RE. 22 of 34 patients were classified BIRADS-US IV and V but in RE malignancy could not be found. The direct comparison between RE and FH showed 39 breast cancers and 13 benign tumors in both methods. 4 FE showed non-malignant tissue while in FH malignant disease were diagnosed. Surprisingly 1 case of cancer in RE could not be confirmed in FH. Cytological analysis showed no reliable results in this study as expected. Conclusions: RE of core-cut-biopsies is a valid method for histological diagnosis of breast lesions. With a sensitivity of 0.91 and a specifity of 0.93 RE is a promising minimal-invasive tool for fast diagnosis and therefore optimal preoperative management. Surprisingly MGr showed only a sensitivity of 0.59 and a specifity of 0.63 in our population.

[P20~ Assessment of breast cancer tumor size depends on method, histopathology and tumor size itself P.A. Faschin.q 1, K. Heusinger 1, C. Loehberg 1 , M.P. Lux 1, T. Papadopoulos 2, K. Imhoff 3, R. Schultz-Wendtland 3, M.W. Beckmann 1 .

i University Hospital Erlangen, Gynecology and Obstetrics, Erlangen, Germany; 2 University of Erlangen, Institute of Pathology, Erlangen, Germany; 3 University of Erlangen, Institute of Diagnostic Radiology, Erlangen, Germany

Purpose: Preoperative staging is gaining importance as neoadjuvant systemic therapy has become an option in the treatment strategy of breast cancer (BC). Mammography (MG), breast (BU) and axillary ultrasound (AU) and clinical examination (CE) are commonly used for clinical staging. In order to assess the accuracy of clinical tumor staging (cT) these different methods were compared. Tumor size estimation was examined dependent on histhopathological features like tumor size, steroid receptor status, HER2/neu-status and proliferation.

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Poster Session L Predictive and Prognostic Factors

Method: From 01/01 to 12/03 a number of 509 BC patients were examined by mammography as initial diagnostics. All these patients were consecutively and prospectively documented concerning mammography, ultrasound and clinical examination. Diagnostic methods were compared to postoperative histopathological and staging parameters. Pearson's correlation was tested for the complete spot check. The deviation of MG, BU and CE to pT was analyzed in subgroups defined by pathological tumor size (pT), grading (G), estrogen receptor (ER), progesteron receptor (PR), proliferation defined by MIB-1 and HER2/neu. Correlation of AU and pN was examined by x2-test. To test the prediction of a pT>2cm Receiver operating characteristics (ROC) were used. Results: Comparing the imaging modalities with pT mammography correlated best with a coefficient r=0,774. Ultrasound revealed a r=0,645 and clinical examination a r=0,698. All correlations were highly significant (p<0,001). Mammography (mean(MG)=2,196cm) overestimated tumors in size (mean(pT)=2,045cm) rather than ultrasound (mean(BU)=1,896cm) and clinical examination (mean(cT)=1,733cm). The size of invasive ductal carcinomas could be estimated significantly better than invasive Iobular tumors as well as smaller tumors and tumors with a Grading GI. None of the other parameters showed significance. Best predictor of a pT>2cm was the mammography with an area under the ROC (AUC) of 0,873. The combination of all three modalities by linear regression performed even better with an AUC of 0,883. Conclusions: All three methods showed accurate means values for the assessment of the tumor size. The dimension of invasive ductal carcinomas, small and low grading tumors is significant better to estimate. Concerning treatment decisions we propose a combination of all three modalities as we could show the best predictive value for the complementary use of mammography, ultrasound and clinical examination. [-~

Semiquantitative analysis of diffuse pattern of 99m Tc-V-DMSA scintimammography in the evaluation of in situ breast carcinomas: A feasible prognostic marker?

V. Papantoniou 1, J. Koutsikos 1, M. Bembi 2, S. Tsiouris 1, M. Sotiropoulou 3, K. Mainta 1, D. Lazaris 4, C. Zerva 1. i Alexandra University Hospital, Nuclear

Medicine Department, Athens, Greece; 2 laso Hospital, Department Of Obstetrics & Gynaecology, Athens, Greece; 3Alexandra University Hospital, Department of Pathology, Athens, Greece; 4Alexandra University Hospital, Department of Obstetrics & Gynaecology, Athens, Greece

Thursday, 27 January 2005 Breast cancer screening of Korean women M. Hur 1, H. Song 1, S. Ko 1, H. Lee 1, S. Kang 1, B. Cho 2, K. Lee 2, J. Lee 1.

i Sungkyungkwan University, School of Medicine, Samsung Cheil Hospital, General Surgery, Seoul, South Korea; 2 Sungkyunkwan University, School of Medicine, Samsung Cheil Hospital, Radiology, Seoul, South Korea

Background: The screening campaigns of breast cancer have been constantly increasing since the benefit of screening in breast cancers had been established. The purpose of this study was to evaluate the efficacy of annual breast screening, which included a mammography and a clinical physical examination. Methods: From March 1995 to July 2004, we performed 110,588 annual clinical examinations and mammographies on 58,024 women, who wanted to undergo breast cancer screening at this breast center. Two hundred fourteen breast cancers were detected during screening, and of these, 161 patients were operated. The results were compared with the ideal rates for medical audits. Results: Of the 110,588 cases screened, the recall rate for further examination was 12.1%(n=13,423). And the biopsy rate was 1.01%(n=1,116). 214 breast cancers were detected; a detection rate of 0.19%. One hundred thirty four patients were the 1 st visitors at this center. The pathologic results of benign disease after biopsies were ordered fibrocystic change, fibroadenoma, adenosis, etc. Invasive ductal cancer is the most common among cancers. Stage 0 among cancers was 23.6%, Stage I was 40.4%, stage II a was 19.9, stage lib and Ilia was 6.2%. Stage IIIc was 3.1%. Also, Stage IV is 0.6%. Positive predictive value(PPV) based on abnormal findings at screening examination was 1.6%(PPV1). PPV when a biopsy or surgical consultation were recommended, was 19.1%(PPV2). Tumor found as stage 0 or I was 64%(103/161). Tumor found as minimal cancer(stage 0 or tumor lesser than lcm) was 38.5%(62/161). There were 38 cases of axillary lymph node metastasis(23.6%). Cancers found per 1,000 cases was 1.7. Prevalence cancer found per 1,000 first examinations was 2.3. Incidental cancer found per 1,000 follow-up examinations was 1.2. These results were compatible with the ideal rates for medical audits, except for PPV1, PPV2, cancers found per 1,000 cases. Conclusion: This breast cancer screening was properly performed. These findings indicate that breast cancer screening using a clinical examination and a mammography is very effective in the early detection of breast cancer.

Aim: To assess the ability of diffuse accumulation of 99m Tc-V-DMSA to image in situ breast carcinoma visually and semi-quantitatively. Materials and methods: A total of 71 women (mean age 62.5 years) that referred with suspicious breast lesions on physical examination and/or an abnormal mammogram, underwent 99m Tc-V-DMSA scintimammography prior to any surgical intervention. Lateral prone and anterior supine images were acquired at approximately 10 and 60 min after administration of 925-1110 MBq of the radiotracer. Increased focal radiotracer accumulation, as compared to surrounding tissue, was assessed as suggestive of invasive cancer. Diffuse increased accumulation was considered as suggesting in-situ carcinoma and further analyzed semi-quantitatively with Tumor/Background (T/B) ratio and compared (t-test) between 10 and 60 min. Scintigraphic results and T/B ratio were compared(t-test) with the presence or absence of microcalcifications in mammograms. Results: Breast cancer was histologicaly confirmed in 43/71 patients (invasive cancer in 24 and in situ cancer (with or without invasive component) in 19 patients). Diffuse V-DMSA pattern was presented in 30 patients: 18/19 pts with in situ carcinomas (16 DCIS, 2 LCIS), 2/24 pts with invasive cancer (microcentric ductal carcinoma) and 10/28 pts with benign lesions associated with epithelial hyperplasia. The sensitivity, specificity, accuracy, positive and negative predictive value for in situ carcinoma were 95%, 77%, 82%, 60% and 98% respectively. The diffuse pattern of in-situ demonstrated a tendency to increase over time (T/B10 min 1.274-0.22 vs. T/BC0 min 1.764-0.25; P<0.01 ). On the contrary, the focal uptake in invasive cancer did not increase significantly (T/B10 min 1.764-0.28 vs. T/BC0 min 1.94-0.28; P>0.05). Mammography depicted suspicious microcalcifications in only half of in-situ cases (10/19; 53%). The diffuse uptake was significantly higher in in-situ patients with microcalcifications, as compared to those without (T/BC0 min 1.814-0.05 vs. 1.44-0.07; P=0.003). Conclusion: The findings of this study indicate the potential value of 99m Tc-V-DMSA scintimammography in imaging in situ breast carcinomas. The semiquantitative analysis of diffuse pattern of 99mTc-V-DMSA scintimammography in combination with mammographic findings could provide useful preoperative information.

THURSDAY, 27 JANUARY 2005

Predictive and Prognostic Factors IP231 Hypermethylation of E-cadherin, GSTP1, 14-3-3~ and TIMP-3 genes as prognostic markers in invasive ductal breast carcinoma Louis w.C. Chow, Eric L.H. Lui, Wings T.Y. Loo, Mary N.B. Cheung.

Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong DNA hypermethylation of TSGs is an important cause of cancer formation. Different types of cancers have different sets of regional-hypermethylated TSGs (hypermethylation patterns), resulting in each tumor type having distinctive characteristics. The hypermethylation status of many TSGs, which is potentially responsible in causing IDC, were investigated in this study and they were correlated with the clinical pathological records of the corresponding cancer patients. 155 samples of IDC were collected, each of which had DNA extraction and MSP performed preceded by pathological examination. The percentage of hypermethylated TSGs were: Ecad 18.42%, GSTP1 31.71 %, 14-3-3s 94.97% and TIMP3 20.81%. Within the above groups, Ecad had a strong positive correlation with lymph node metastasis. Hypermethylation of GSTP1 and TIMP3 and 14-3-3s was associated with HER2 overexpression and high tumor grade. The four TSGs tested may serve as potential markers for the corresponding characteristics of IDC since they were related to some of the histopathological status. Our observations also suggested that HER2 might potentially induce hypermethylation of Ecad gene.