A Randomized Phase IIb Study of Low-dose Tamoxifen in Chest-irradiated Cancer Survivors at Risk for Breast Cancer.

PURPOSE: Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors-a population with breast cancer risk comparable with BRCA mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk. PATIENTS AND METHODS: We conducted an investigator-initiated, randomized, phase IIb, double-blinded, placebo-controlled trial (FDA IND107367) between 2010 and 2016 at 15 U.S. sites. Eligibility included ≥12 Gy of chest radiation by age 40 years and age at enrollment ≥25 years. Patients were randomized 1:1 to low-dose tamoxifen (5 mg/day) or identical placebo tablets for 2 years. The primary endpoint was mammographic dense area at baseline, 1 and 2 years. IGF-1 plays a role in breast carcinogenesis; circulating IGF-1 and IGF-BP3 levels at baseline, 1 and 2 years served as secondary endpoints. RESULTS: Seventy-two participants (low-dose tamoxifen: n = 34, placebo: n = 38) enrolled at a median age of 43.8 years (35-49) were evaluable. They had received chest radiation at a median dose of 30.3 Gy. Compared with the placebo arm, the low-dose tamoxifen arm participants had significantly lower mammographic dense area (P = 0.02) and IGF1 levels (P < 0.0001), and higher IGFBP-3 levels (P = 0.02). There was no difference in toxicity biomarkers (serum bone-specific alkaline phosphatase, lipids, and antithrombin III; urine N-telopeptide cross-links) between the treatment arms. We did not identify any grade 3-4 adverse events related to low-dose tamoxifen. CONCLUSIONS: In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer risk and could serve as a risk-reduction strategy.

Comparison of screening performance metrics and patient dose of two mammographic image acquisition modes in the Danish National Breast Cancer Screening Programme.

INTRODUCTION: In this study, screening performance metrics and radiation dose were compared for two image acquisition modes for breast cancer screening with MAMMOMAT Inspiration (Siemens Healthcare GmbH, Forchheim, Germany). This mammography system can operate without an anti-scatter grid in place but using software scatter correction instead. This grid-less acquisition mode (PRIME) requires less patient dose due to the increase in primary radiation reaching the detector. This study retrospectively analyses data from the Region of Southern Denmark where the grid-less mode has been installed in November 2013 and replaced grid-based screening. METHODS AND MATERIALS: A total of 72,188 screening cases from the same geographical region in Denmark were included in the study. They were subdivided into two study populations: cases acquired before and after installation of the grid-less acquisition mode. Sensitivity and specificity of breast cancer screening were calculated for the two populations; thus representing the performance of grid-less and grid-based screening. To measure the entrance surface air kerma (ESAK) additional phantom tests were carried out. Polymethylmethacrylate (PMMA) attenuation plates with different thicknesses (20-70 mm in steps of 10 mm) simulated the compressed breast (21 mm-90 mm) and a solid-state dosimeter was used. RESULTS: Statistical testing of the results showed that screening with grid-less acquisition provides equivalent performance with respect to sensitivity and specificity compared to grid-based screening. The specificity was 98.11% (95% confidence interval (CI) from 97.93% to 98.29%) and 97.96% (95% CI from 97.84% to 98.09%) for screening with grid-less acquisition and grid-based acquisition, respectively. The cancer detection rate as a measure for sensitivity was equal (0.55%) for grid-less screening and grid-based screening. An average glandular dose saving between 13.5% and 36.4% depending on breast thickness in grid-less acquisition was obtained compared to grid-based acquisition. CONCLUSION: Statistically significant equivalence was shown with an equivalence margin of 0.12% points for cancer detection rate and with an equivalence margin of 0.40% points for specificity. A marked patient dose savings in grid-less acquisition of up to 36% compared to grid-based acquisition was achieved. It can be concluded that grid-less acquisition with software scatter correction is an alternative to grid-based acquisition in mammography.