Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

BACKGROUND: To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. PATIENTS AND METHODS: A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. RESULTS: Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). CONCLUSIONS: In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

Scintimammography with 99mTc-MDP in the detection of primary breast cancer.

MATERIALS AND METHODS: The diagnostic accuracy of scintimammography with 99mTc-MDP was evaluated in 400 consecutive women with clinical or mammographic suspicion of breast cancer, candidate to surgery and/or excisional biopsy. Lateral views of both glands were acquired, in prone position, 5-10 min after the injection of 550-740 MBq of 99mTc-MDP. The scintigraphic results were compared to mammograms and classified using the histological findings as gold standard. RESULTS: Mammography was suggestive for cancer in 231 (57%), suspicious in 49 (12%) and indeterminate in 120 (31%) patients. Breast carcinoma was histologically proven in 330 women, benign breast diseases in 70. The tumor size ranged from 4 x 5 to 50 x 60 mm. 99mTc-MDP visualized as foci of increased uptake 305/330 cancers (92%). In particular, in women with indeterminate mammograms the SMM had a diagnostic accuracy of 84%, correctly characterizing 101/120 lesions. Twenty missed cancers had largest diameter < or = 10 mm, 5 < or = 15 mm. Lack of 99mTc-MDP uptake occurred in 64 out of 70 benign lesions. These lesions were classified as truly negative. Conversely, 3 fibroadenoma and 3 epithelial hyperplasia with moderate or severe atypia were falsely positive. The overall specificity was 91.5%; the accuracy was 92%, the positive and negative predictive values were respectively 98% and 72%. CONCLUSIONS: The results obtained in this study suggest that 99mTc-MDP scintimammography accurately detects breast carcinomas with largest diameter > 10 mm; it differentiates malignant from benign lesions, and it shows promising insights in characterizing breast abnormalities mammographically indeterminate.