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

Stereological quantification of placental villus vascularization and its relation to umbilical artery Doppler flow in intrauterine growth restriction

WOS: 000175737500013PubMed ID: 12001195The aim of this study was to investigate the changes in the number of vessels within tertiary stem villi and intermediate/terminal villi Which may be responsible for the abnormalities in placental vascular resistance and Doppler velocity index values in growth-restricted fetuses. The placentas of 20 cases with intrauterine growth restriction and 30 cases Which Were appropriate for gestational age Were Studied. The umbilical artery resistance index, pulsatility index and systolic to diastolic ratio Were Measured in each case. The vessels Were quantified by a stereological method described previously and vascular surface density and the volume portion of the villi Were calculated. The placentas of preterm and term cases With intrauterine growth restriction displayed significant reductions in the vascular surface density of stem and intermediate/terminal villi and volume portion of intermediate/terminal villi stroma Mien compared Both gestation-matched normally grown cases (p0.05). Some of the pregnancies with intrauterine growth restriction (six patients) with normal Doppler flow velocity waveforms had reduced vascularization in the placentas. and these pregnancies Were found to have no perinatal complications. We conclude that. although the placental villi show reduced vascularization in pregnancies with intrauterine growth restriction, the Doppler indices may be normal and this normal flow pattern is related to reduced complication rate. Copyright (C) 2002 John Wiley Sons, Ltd