Rapid Reductions in Breast Density following Tamoxifen Therapy as Evaluated by Whole-Breast Ultrasound Tomography

Abstract

Purpose: Women whose mammographic breast density declines within 12–18 months of initiating tamoxifen for chemoprevention or adjuvant treatment show improved therapeutic responses compared with those whose density is unchanged. We tested whether measuring changes in sound speed (a surrogate of breast density) using ultrasound tomography (UST) could enable rapid identification of favorable responses to tamoxifen. Methods: We evaluated serial density measures at baseline and at 1 to 3, 4 to 6, and 12+ months among 74 women (aged 30–70 years) following initiation of tamoxifen for clinical indications, including an elevated risk of breast cancer (20%) and diagnoses of in situ (39%) or invasive (40%) breast carcinoma, enrolled at Karmanos Cancer Institute and Henry Ford Health System (Detroit, MI, USA). For comparison, we evaluated an untreated group with screen negative mammography and frequency-matched on age, race, and menopausal status (n = 150), at baseline and 12 months. Paired t-tests were used to assess differences in UST sound speed over time and between tamoxifen-treated and untreated patients. Results: Sound speed declined steadily over the 12 month period among patients receiving tamoxifen (mean (SD): −3.0 (8.2) m/s; p = 0.001), whereas density remained unchanged in the untreated group (mean (SD): 0.4 (7.1) m/s; p = 0.75 (relative change between groups: p = 0.0009)). In the tamoxifen group, we observed significant sound speed reductions as early as 4–6 months after tamoxifen initiation (mean (SD): −2.1 (6.8) m/s; p = 0.008). Sound speed reductions were greatest among premenopausal patients (P-interaction = 0.0002) and those in the middle and upper tertiles of baseline sound speed (P-interaction = 0.002). Conclusions: UST can image rapid declines in sound speed following initiation of tamoxifen. Given that sound speed and mammographic density are correlated, we propose that UST breast imaging may capture early responses to tamoxifen, which in turn may have utility in predicting therapeutic efficacy.