20. Clinical and radiological predictors of complete excision in breast conserving treatment (1995)

s of the 4th Nottingham International Breast Cancer Conference 233 carried out safely without radical excision, while excluding only a small proportion of patients. 20. Clinical and radiological predictors of complete excision in breast conserving treatment P. G. Gill, B. Beamond, H. Rossi, M. L. Carter, S. Langlois, P. Malycha, B. Coventry, J. Walsh Royal Adelaide Hospital, Adelaide, Australia Local recurrence (LR) following conservative surgery for breast cancer usually results from growth of residual cancer adjacent to the excised primary tumour, or of multifocal disease. Complete excision (CLE) confirmed histologically is essential in ensuring that the risk of LR is minimal. This study was undertaken to determine what factors may assist the surgeon at the time of operation to achieve this aim. A retrospective review of 101 cases treated by conservative surgery identified 70 cases of CLE and 31 of incomplete excision. Clinical, surgical and pathological data were derived from the hospital records. Mammographic features and those of specimen X-rays were evaluated without knowledge of the pathological outcome of surgery. Complete excision (CLE) was significantly associated with type of operation (P < 0.003), the absence of calcification on X-ray (P < 0.03), and the presence of a mass on mammography (P < 0.03). Extensive DCIS was associated with incomplete excision (P < 0.01). No relationship was demonstrated with age, breast size and density, tumour size and grade, receptor status and axillary nodal status or spiculations on X-ray. Specimen X-ray had a positive predictive value for CLE of 97% and should be further evaluated as an aid to achieving CLE, in addition to the clinical and mammographic features of the tumour. 21. Chronology and biology of breast cancer: the influence of screening T. J. Anderson, A. L. Hubbard, R. A. Hawkins, J. M. Dixon, E. D. Anderson, F. E. Alexander Departments of Pathology, Surgery and Public Health Sciences, The University of Edinburgh, and South East Scotland Breast Screening Centre, Edinburgh, UK The introduction in Edinburgh of UK Service Screening for Breast Cancer following the Edinburgh Randomized Trial has enabled comparative evaluations of pathological characteristics in breast cancers occurring in women aged 50-64 years with differing screening exposure. A consecutive series of 235 such cases from 1988 to the end of 1990 represent a crosssectional study incorporating women that were newly, previously and never screened. Features compared between these groups were those regarded primarily as chronologically determined (invasive size and node status) and those primarily biologically determined (histological type and grade, DNA ploidy, c-erbB-2 gene disregulation and oestrogen receptor (ER) status). The ‘chronological’ features differed significantly between the 3 screening categories whereas ‘biological’ features were no less favourable in never screened than ever screened women. However, advancement of diagnosis into the detectable preclinical phase reduced the degree of c-erbB-2 amplified copy, indicating that biological factors could be influenced by screening. There was also a strong interrelationship between ER status and C-erbB-2 ‘status’. The overall findings contribute to a better understanding of breast cancer natural history. The influence of current mammographic screening towards cancer detection at a less aggressive phase appears limited. 22. A new model of human mammary epitbelial apoptosis R. A. Harris, I. Hiles, M. Page, M. J. O’Hare Wellcome Research Laboratories, Beckenham, Kent and Department of Surgery, UCLMS, London, UK Homeostatic growth regulation in the normal mammary gland is a function of cell proliferation and apoptosis. While numerous studies have addressed the question of regulation of mammary epithelial cell growth, few have explored the mechanisms controlling mammary apoptosis. We report here a new in vitro model in which apoptosis can be rapidly and uniformly induced, and which can be abrogated using hormones. An immortalized but non-transformed mammary cell line (HB4a) derived from flow-sorted normal human breast luminal epithelial cells has been transfected with the rat neu oncogene which has been activated by point mutation. The resulting line (N4.1) not only exhibited transformed characteristics in culture, but also underwent apoptosis, as defined by both morphological and molecular criteria, when subject to serum starvation. Studies with a wide range of growth factors and hormones showed that glucocorticoids were able to abrogate this apoptotic response at physiological concentrations. These results implicate, for the first time, aberrant receptor tyrosine kinases in apoptotic signalling pathways. 23. Does paratbyroid hormone related protein (PTHrP) cause microcalcification in breast cancer? J. Walls, S. E. Downey, W. A. Ratcliffe, C. R. M. Boggis, F. Knox, N. J. Bundred Departments of Surgery, Radiology and Pathology, University Hospital of South Manchester and Wolfson Research Laboratories Birmingham, UK Mammographic microcalcification occurs in 40% of breast cancer. Parathyroid hormone related protein (PTHrP) initiates calcification in the eggshells of birds oviducts and we have investigated whether PTI-IrP is responsible for microcalcification in breast cancer. Microcalcification was assessed radiologically by a consultant radiologist and histologically using haematoxylin and eosin sections of 185 screen detected breast cancers. Immunohistochemical detection of PTHrP was carried out with a polyclonal rabbit anti serum to 36-67 PTHrP. Assessment of staining was by two independent observers, one of whom was a consultant pathologist. PTHrP was expressed in 110/185 breast cancers in their cytoplasm. Microcalcification was seen significantly more often in PTHrP positive tumours (see table; P c 0.001). Breast (n) Mammographic Histological cancers microcalcification microcalcitication PTHrP Positive 110 52(50%) 25(24%) *P 5 0.001 Negative 75 16(21%) S(ll%) PTHrP Produced by breast tumours is responsible for microcalcification seen mammographically. 24. Synthesis and secretion of TGFb isoforms by breast tumour fibroblasts in vitro and modulation by tamoxifen J. R. Benson, M. Baum, A. A. Colletta Section of Academic Surgery, The Royal Marsden Hospital, London, UK