Abstract Background: Systemic therapies for breast cancer (BC) can lead to cancer treatment-induced bone loss (CTIBL), increase fracture risk, impair the quality of life, and potentially worsen prognosis. Although CTIBL prevention has been established in postmenopausal patients with BC, CTIBL in premenopausal women remains unclear owing to the limited number of reports. Chemotherapy often induces ovarian suppression and estrogen deficiency, thereby accelerating bone loss. Furthermore, the effects of tamoxifen on the bone are yet to be established in premenopausal patients with BC. In this study, we prospectively evaluated CTIBL in premenopausal patients with BC by monitoring bone mineral density (BMD), hormones, and bone turnover markers. Methods: We recruited 64 premenopausal females diagnosed with early-stage BC. We compared patients receiving tamoxifen monotherapy (T group, n=19; median age, 45 range, 37-55 years) with those receiving chemotherapy followed by tamoxifen therapy (C group, n=31; median age, 45 years range, 31-50 years). BMD at the lumbar spine and femoral neck was measured at baseline, immediately after chemotherapy (C group), and at 6, 12, and 18 months after tamoxifen initiation. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), bone turnover markers, procollagen type 1 N-terminal propeptide (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and undercarboxylated osteocalcin (ucOC) were concurrently assessed to evaluate hormonal and metabolic effects on bone health. Results: 1. BMD Changes: T group: The changes(±SD) in BMD were minimal, with a 2.2±5.1% decrease (p=0.13) at the lumbar spine and a 1.6±4.4% increase(p=0.19) at the femoral neck at 24 months.C group: Lumbar spine BMD decreased by 2.4±3.9% post-chemotherapy (p=0.0057) and by 3.4±3.1% at 24 months (p=0.0060). Femoral neck BMD decreased by 1.3±4.6% post-chemotherapy (p=0.24) and 4.1±4.1% at 24 months (p=0.0047). 2. Hormonal Changes: T group: E2 increased by 328.1±385.6% at 6 months (p=0.003) but returned to baseline by 24 months. FSH levels showed no significant changes.C group: E2 decreased by 76.2±49.6% post-chemotherapy (p0.001), with no significant differences observed at 24 months. FSH increased by 1061.1±890.7% post-chemotherapy (p0.001), gradually decreased, and remained 53.6±89.8% above baseline at 24 months (p=0.038). 3. Bone Turnover Markers: T group: P1NP and TRACP-5b levels showed no significant changes over 24 months (all p 0.05). ucOC decreased by 22.6±36.5% at 6 months (p=0.036), stabilizing thereafter.C group: P1NP increased by 98.9±90.0% post-chemotherapy (p0.001) and gradually returned to baseline levels by 24 months (-5.4±45.0%, p=0.90). TRACP-5b increased by 89.9±106.6% post-chemotherapy (p0.001) and gradually returned to baseline levels by 24 months (5.7±44.3%, p=0.38). ucOC decreased by 82.6±11.5% post-chemotherapy (p0.001) and remained suppressed, with no significant recovery observed at 24 months (-89.1±9.2%, p0.001). Conclusions: The C group showed significant and sustained reductions in BMD. The observed bone loss could be attributed to chemotherapy-induced ovarian suppression and estrogen deficiency. Increased bone turnover markers were consistent with a high bone resorption state and bone loss. Conversely, BMD was preserved in the T group, consistent with stable hormone levels and bone turnover markers. These findings indicate the need for proactive bone health management, including regular BMD monitoring and consideration of bone-protective treatments, especially in premenopausal patients with BC receiving chemotherapy, to improve long-term quality of life without fracture. Citation Format: A. Nishikawa, K. Narui, Y. Fujiwara, Y. Shibata, S. Adachi, K. Kawashima, M. Oshi, A. Yamada, H. Yoshikata, T. Tsuburai, I. Endo. Effects of cancer treatment on bone mineral density in premenopausal patients with early-stage breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-03-18.
Nishikawa et al. (Tue,) studied this question.