SummaryBackgroundInitial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial.MethodsWomen with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870.FindingsBetween May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9–14·7), 376 (163 invasive [122 ipsilateral vs 39 contralateral], 197 DCIS [174 ipsilateral vs 17 contralateral], and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio [HR] 0·41, 95% CI 0·30–0·56; p<0·0001), reducing the incidence of ipsilateral invasive disease (0·32, 0·19–0·56; p<0·0001) as well as ipsilateral DCIS (0·38, 0·22–0·63; p<0·0001), but having no effect on contralateral breast cancer (0·84, 0·45–1·58; p=0·6). Tamoxifen reduced the incidence of all new breast events (HR 0·71, 95% CI 0·58–0·88; p=0·002), reducing recurrent ipsilateral DCIS (0·70, 0·51–0·86; p=0·03) and contralateral tumours (0·44, 0·25–0·77; p=0·005), but having no effect on ipsilateral invasive disease (0·95, 0·66–1·38; p=0·8). No data on adverse events except cause of death were collected for this trial.InterpretationThis updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision.FundingCancer Research UK and the Australian National Health and Medical Research Council.

Objectives To describe the effect of multidisciplinary care on survival in women treated for breast cancer.Design Retrospective, comparative, non-randomised, interventional cohort study.Setting NHS hospitals, health boards in the west of Scotland, UK.Participants 14 358 patients diagnosed with symptomatic invasive breast cancer between 1990 and 2000, residing in health board areas in the west of Scotland. 13 722 (95.6%) patients were eligible (excluding 16 diagnoses of inflammatory cancers and 620 diagnoses of breast cancer at death).Intervention In 1995, multidisciplinary team working was introduced in hospitals throughout one health board area (Greater Glasgow; intervention area), but not in other health board areas in the west of Scotland (non-intervention area).Main outcome measures Breast cancer specific mortality and all cause mortality.

SummaryThe expression of the c-erbB-2 oncogene has been evaluated using an immunohistochemical technique with the 21N polyclonal antibody in paraffin embedded tissue from 465 patients treated between the years [1975][1976][1977][1978][1979][1980][1981] for Stage I and II breast cancer. One hundred and four (22%) patients exhibited positive staining. This was not associated with any other variables. Expression of the oncogene was associated with significantly poorer survival which was independent of other tumour variables.The proto-oncogene c-erbB-2 encodes a protein present at the cell surface which has considerable homology with the epidermal growth factor receptor EGFR (Coussens et al., 1985). Although originally identified as an oncogene in chemically induced neuroblastomas in rats (Pahdy et al., 1982;Bargmann et al., 1986), recent interest has focused on its role in human breast cancer. Studies on cell lines derived from human mammary carcinomas have demonstrated that c-erbB -2 can be overexpressed by several mechanisms including gene amplification (Kraus et al., 1987) and this is present in up to 30% of human breast cancers (Slamon et al., 1987;van de Vijver et al., 1987;Varley et al., 1987;Zhou et al., 1987).The development of both polyclonal and monoclonal antibodies to the oncoprotein has allowed its distribution to be evaluated in histological sections, and its presence and clinical significance to be correlated with amplification of its gene and expression of its mRNA (Venter et al., 1987;van de Vijver et al., 1987;Slamon et al., 1989;Gusterson et al., 1988). These studies have confirmed that both gene amplification and increased transcription of its mRNA are associated with expression of this putative receptor at the cell surface in patients with breast cancer. One study though has reported that 20% of patients expressing this receptor failed to exhibit a corresponding amplification of its gene (Berger et al., 1988) and has concluded that other mechanisms may also be of importance in allowing it to be expressed.In both molecular studies and those based on immunological detection of the protein expression of the receptor has been associated with the spread of tumour to the axillary lymph nodes, to the number of nodes involved (Zhou et al., 1987;Slamon et al., 1987Slamon et al., , 1989, larger tumours (van de Vijver et al., 1987) and with poor histological grade (Berger et al., 1988). However, the number of patients assessed in these studies is variable and some have contained too few patients to evaluate the statistical significance of the data. Reports of its clinical significance have been conflicting, with some investigators noting a poorer prognosis in patients expressing the protein (Slamon et al., 1989;Wright et al., 1989a; Lovekin et al., 1989) and others reporting little difference (Barnes et al., 1988;Zhou et al., 1989; Alli et al., 1988;Gusterson et al., 1988 obtained. In addition, blocks were obtained from 100 patients with both benign fibrocystic disease and fibroadenomas who had undergon...

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