Tumour suppressor function of CHIP & LOX in human breast cancer

ABSTRACTS leaving 71 with normal mammograms to be reviewed. The reason for recall, further investigations and diagnosis after assessment were noted. Results: The symptoms, prompting recall were, a breast lump (33/ 71,47%), nipple changes (25/71,35%), breast pain (12/71,17%) and skin dimpling (1,1%). Of these ladies 48(68%) were considered normal on clinical examination. Further imaging was performed in 12(17%) ladies, 1 MRI and 11 ultrasound scans. Ten patients had samples sent for histology, 4 core and 6 punch biopsies. After full assessment 70(99%) of patients had benign or normal results and were returned to the NHSBSP. Only 1(1%), with a nipple abnormality, had a diagnosis of cancer and underwent a mastectomy. Conclusion: These results show that when the screening mammogram is normal the detection rate for breast cancer based on symptoms is only 1%. Recall should be selective based on the symptoms mostly likely to represent breast cancer.

P129. Sentinel Lymph node biopsy in breast cancer: How many nodes should we remove? Roslyn Pursell, J. Gill, R. Lovegrove, K. Naessens, T. Cominos, C. McCormick Royal Berkshire Hospital, London Road, Reading, Berkshire, RG1 5AN Aims: Sentinel node biopsy (SNB) is now the standard of care in assessment of T1-2, N0 breast cancers. This study investigates whether there is a maximum number of sentinel lymph nodes (SLN) that need to be excised without compromising the false negative (FN) rate of this procedure. Methods: Data was prospectively collected for 319 patients undergoing SNB between February 2001 and December 2006 at our institution. This data was analysed, both in terms of the order of SLN retrieval and relative isotope counts of the SLNs, in order to determine the maximum number of SLNs that need to be retrieved without increasing the FN rate. Furthermore we investigated the relationship between SLN blue dye intensity and the presence of SLN metastases. Results: The SLN identification rate was 97.2% with no false negative cases. In patients with SLN metastases, excision of the first 4 SLNs encountered results in the identification of a metastatic SLN in all cases. Although the majority (85.6%) of SNB metastases are in the hottest node, the SLN containing the metastasis is in the first four hottest nodes in 98.8% of patients with nodal metastases. The remaining 1.2% of SLN metastases were identified by blue dye. There was no statistically significant association between the SLN blue dye concentration and the presence of SLN metastases. Conclusion: A policy to remove a maximum of 4 SLNs does not result in an increased false negative rate of detection of SLN metastases.

P130. Tumour suppressor function of CHIP & LOX in human breast cancer Neill Patania, W. Jiangb, K. Mokbelc a The London Breast Institute, The Princess Grace Hospital, 45 Nottingham Place, London, W1U 5NY b University Department of Surgery, Wales College of Medicine, Cardiff University c St. George’s University, London Breast Institute, Brunel Institute of Cancer Genetics Background: Ubiquitin modification influences diverse cellular processes including protein stability. CHIP (carboxyl terminus Hsc70-interacting protein) is a ubiquitin ligase implicated in the modulation of oestrogen receptor and Her-2/neu stability. Lysyl-oxidase (LOX) is a catalyst for cross-linking collagens and elastin within the extra-cellular matrix. Altered expression has been demonstrated in several malignancies and the peri-tumoural stroma. In this study, mRNA expression of CHIP and LOX were assessed in a cohort of breast cancers and correlated to clinico-pathological parameters over a 10 year follow-up period.

1239 Methods: Breast cancer (n ¼ 115) and normal background tissues (n ¼ 31) were collected after excision. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR (normalized against CK19). Results: CHIP expression decreased with increasing Nottingham Prognostic Index (NPI): NPI-1 vs. NPI-3 (12.2 vs. 0.2, p ¼ 0.0264), NPI-2 vs. NPI-3 (3 vs. 0, p ¼ 0.0275), TNM stage: TNM-1 vs. TNM-2 (12 vs. 0, p ¼ 0.0639), TNM-1 vs. TNM-2,3,4 (12 vs. 0, p ¼ 0.0434) and tumour grade: grade 1 vs. grade 3 (17.7 vs. 0.3, p ¼ 0.0266), grade 2 vs. grade 3 (5 vs. 0, p ¼ 0.0454). The overall survival (OS) for tumours classified as ‘low level expression’ was better than ‘high level expression’ (118.1 vs. 152.3 months, p ¼ 0.039). LOX expression decreased with increasing NPI: NPI-1 vs. NPI-2 (3 vs. 0, p ¼ 0.0301) and TNM stage: TNM1 ¼ 3854639, TNM-2 ¼ 908900, TNM-3 ¼ 329, TNM-4 ¼ 1.2 (p ¼ NS). Conclusion: CHIP expression is significantly associated with favourable parameters, including tumour grade, TNM stage, NPI and OS. LOX expression is associated with an improved NPI. P131. Audit of Blue dye guided axillary surgery Sankaran ChandraSekharan, S. Marsh, I. Anwar Essex County Hospital, Lexden Road, Colchester, CO3 3NB Aim: The aim of the audit was to look at the accuracy of using blue dye alone for identifying Sentinel nodes and to look at false negative rates. Background: We are currently in the audit phase of the Almanac study. All patients having axillary surgery (who are not in the Almanac study) will have blue dye injected at time of operation. The MDT prior to operation will have decided whether patients are having a sample or full dissection. Results: We have looked at 527 patients (2003-2008) who have had only blue dye guided axillary surgery. In 507 (96.2%) the blue node was identified. Out of these 225 had positive nodes and 282 had negative nodes. Of the 282, 14 had false negative nodes (5.85%). In the fourteen patients 8 had heavy nodal disease of more than 5 nodes positive, 3 had 2 nodes positive and 3 had one positive node. In the 20 patients where no blue node was identified 13 had negative axillary nodes and 7 had positive nodes Discussion and conclusion: The combined method is considered as the gold standard for SLNB. In our unit we found that using blue dye alone our Sentinel node pick up rate (96.2%) and the false negative rate (5.85%) is very acceptable and compares well with the combined technique. In district general hospitals where getting gamma camera time may be a problem using blue dye alone may be a good alternative in the hands of experienced breast surgeons. P132. Single dose radiotherapy during surgery for breast cancer patients where external beam radiation was not feasible - results after 3 years of follow-up Mohammed Keshtgara, J. Vaidyab, C. Staceyc, J. Tobiasc, N. Williamsd, M. Baumd a Royal Free Hospital, Pond Street, London, NW3 2QG b Whittington Hospital, London c UCLH, London d Clinical Trials Group, UCL Medical School, London Introduction: Intra-operative radiotherapy (IORT) with IntrabeamÒ (Carl Zeiss, Germany) has been used since 2000 in the international randomised TARGIT Trial to determine if there is equivalence between the novel IORT technique and conventional external beam radiotherapy (EBRT) in women with early breast cancer. Some patients were unsuitable for inclusion in our trial for a number of reasons and were given IORT as a single treatment off-trial. Methods: Patients with invasive breast cancer underwent wide local excision followed by IORT (n ¼ 74). Low energy x-rays are emitted from the point source, delivering 20 Gy radiation dose to the breast tissue at the surface of the tumour bed. Radiotherapy is delivered directly into the area of interest, following which women can then proceed to have chemotherapy and/ or adjuvant hormonal therapy as required. In addition, patients who were