Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Choice of agent and prediction of systemic toxicity in isolated hyperthermic limb perfusion

Between 1985 and 1989 35 isolated hyperthermic limb perfusions were performed for melanoma confined to the extremities. Twenty-six perfusions were performed using melphalan, 1-2 mg/kg (9 adjuvant, 17 therapeutic) and 9 using cisplatin 75-150 mg/m² (all therapeutic). Recurrent tumour was not excised to provide evidence of objective response to the cytotoxic agent. During 24 such perfusions I-125 labelled human serum albumin (HSA) leakage from the perfusion circuit was measured and correlated with observed systemic toxicity. A response to melphalan was seen in 15/17 patients (88%): 13/15 complete responses and 2/15 partial responses; and in 3/9 patients (33%): 2/3 complete and 1/3 partial responses, perfused with cisplatin. Duration of response after melphalan ranged from 5 months to 48 months and after cisplatin from 4 to 19 months. Bone marrow depression was seen in 8 cases; all had received melphalan. Systemic toxicity was predicted by high leak rates of I-125 HSA after 10 min (P < 0.05). Melphalan remains the drug of choice in isolated hyperthermic limb perfusion for malignant melanoma and systemic toxicity from the drug may be predicted by I-125 HSA studies

Analysis of the genes for oestrogen and epidermal growth factor receptors in human breast cancer

One of the consistent observations in the investigation of human breast cancer is the finding of an inverse relationship between oestrogen (ER) and epidermal growth factor (EGFR) receptors. The precise mechanisms responsible for this relationship are not fully understood. In order to examine whether genomic alterations make any contribution to this relationship we have examined the genes of these two receptors in 58 primary breast cancer patients using the techniques of Southern blotting and deoxyribonucleic acid (DNA) slot blotting and compared them to their respective proteins which were quantified using immunocytochemistry. Immunocytochemical analysis in 53 of these cases confirmed the existence of a strong inverse relationship between ER and EGFR (P < 0.001). DNA slot blot analysis revealed that the levels of both genes formed a normal distribution comparable to levels found in normal volunteers. Hence, no evidence of gene amplification for either ER or EGFR was observed. Southern blot analysis using EcoR1 restriction endonulcease digestion in 44 of these cases revealed no restriction fragment length polymorphisms (RFLPs) of the ER gene. RFLPs of the EGFR gene were observed but these have previously been demonstrated to be of no clinico-pathological relevance. From the results of this study it appears that amplification or alterations, using EcoR1 restriction endonuclease digestion, in either the ER or EGFR genes are unlikely to contribute to the inverse relationship in vivo. This contrasts with previous observations in tumour cell lines

TELEMAM: a cluster randomised trial to assess the use of telemedicine in multi-disciplinary breast cancer decision making.

AIM: The TELEMAM trial aimed to assess the clinical effectiveness and costs of telemedicine in conducting breast cancer multi-disciplinary meetings (MDTs). METHODS: Over 12 months 473 MDT patient discussions in two district general hospitals (DGHs) were cluster randomised (2:1) to the intervention of telemedicine linkage to breast specialists in a cancer centre or to the control group of 'in-person' meetings. Primary endpoints were clinical effectiveness and costs. Economic analysis was based on a cost-minimisation approach. RESULTS: Levels of agreement of MDT members on a scale from 1 to 5 were high and similar in both the telemedicine and standard meetings for decision sharing (4.04 versus 4.17), consensus (4.06 versus 4.20) and confidence in the decision (4.16 versus 4.07). The threshold at which the telemedicine meetings became cheaper than standard MDTs was approximately 40 meetings per year. CONCLUSION: Telemedicine delivered breast cancer multi-disciplinary meetings have similar clinical effectiveness to standard 'in-person' meetings

A comprehensive approach for evaluating telemedicine-delivered multidisciplinary breast cancer meetings in southern Scotland.

Multidisciplinary team (MDT) meetings for decisions on cancer management are a cornerstone of UK cancer policy. We have proposed a comprehensive methodology to assess the clinical and economic effectiveness of telemedicine in this setting, which is being tested in a randomized breast cancer trial. Pre- and post-telemedicine assessment includes attitudes to and expectations of telemedicine, based on semistructured interviews. The communication content of videotapes of the MDT meeting is being scored using Borgatta's revised Interaction Process Analysis System. The technical performance of the telemedicine equipment is reported on a standardized pro forma. A short questionnaire captures key elements of professional satisfaction for each patient discussion (consensus on future management, confidence in and sharing of decision), added value of linkage, group atmosphere, overall conduct of the meeting and compliance with SIGN guidelines. A cost-minimization analysis will be used for economic assessment