【文章內(nèi)容簡介】 Early Breast Cancer: Endocrine Therapy ZFAST: Upfront vs Delayed ZA Brufsky A, et al. SABCS 2022. Abstract 27. Postmenopausal women with ERpositive or PgRpositive breast cancer (N = 602) *All patients treated with calcium and vitamin D. ?ZA initiated when Tscore decreased to 2 or clinical fracture occurs. Delayed ZA*? + Letrozole mg/day (n = 301) Upfront ZA* 4 mg IV every 6 months + Letrozole mg/day (n = 301) Early Breast Cancer: Endocrine Therapy ZFAST: Change in BMD for Delayed vs Upfront ZA ? Lumbar spine and total hip BMD increased for patients on upfront ZA but decreased for patients on delayed ZA ? By 36 months, 62 (21%) patients in the delayed arm initiated ZA ? 36month fracture rates: % for upfront arm vs % on delayed ZA arm ? Trend toward less disease recurrence in upfront arm vs delayed arm – 9 (%) vs 16 (%), respectively (P = .13) Brufsky A, et al. SABCS 2022. Abstract 27. 4 3 2 1 0 1 2 3 4 Lumbar Spine BMD Total Hip BMD Change in BMD at 36 Mos (%) P .0001 P .0001 Upfront ZA Delayed ZA Early Breast Cancer: Endocrine Therapy IBISII Substudy: Risedronate vs Placebo for Bone Loss Singh S, et al. SABCS 2022. Abstract 28. *Preliminary results for patients who pleted first year of treatment。 final N will be 1000. ?Tscores at lumbar spine or femoral neck. Observation (n = 227 [112 anastrozole]) Postmenopausal women at high risk for breast cancer (N = 350*) Stratum I (Normal) Tscore ≥ 1? (n = 227) Stratum II (Osteopenic) ≤ Tscore 1? (n = 80) Stratum III (Osteoporotic) 4 Tscore ? (n = 43) Risedronate PO 35 mg weekly (n = 43 [25 anastrozole]) Placebo (n = 37 [13 anastrozole]) Risedronate PO 35 mg weekly (n = 45 [22 anastrozole]) Anastrozole 1 mg/day (n = 175) Placebo (n = 175) IBISII bone substudy Early Breast Cancer: Endocrine Therapy IBIS II Substudy: Decreased BMD With Risedronate vs Placebo at 1 Year Singh S, et al. SABCS 2022. Abstract 28. Mean Change in BMD for lumbar spine at 1 Year (%) 6 4 2 0 2 4 6 STRATUMI Normal BMD No Risedronate STRATUMII Osteopenic Risedronate or Placebo STRATUMIII Osteoporotic All Risedronate P A P P P A P R R A R R A P % % % % % % % % n = 115 112 24 13 18 25 23 22 P = .006 O O ? Results similar when hip BMD measured Early Breast Cancer: Endocrine Therapy Denosumab: Bone Resorption Inhibitor ? Adjuvant AIs more monly used than tamoxifen for postmenopausal hormone receptor–positive breast cancer – Associated with accelerated bone loss and increased fracture risk ? RANKL stimulates osteoclasts and bone resorption ? Denosumab – Novel fully human monoclonal antibody to RANKL – Does not bind TNF?, TNF?, TRAIL, or CD40L – Possible agent to reverse AIinduced bone loss Ellis G, et al. SABCS 2022. Abstract 47. RANKL RANK Bone Cancer Cells in Bone Cytokines and Growth Factors (IL6, IL8, IL1?, PGE2, TNF?, CSF1, PTHrP) Osteoclast Growth Factors (TGF?, IGFs, FGFs, PDGFs, BMPs) Osteoblast Lineage Direct effects on tumor? Bone Resorption RANKL Early Breast Cancer: Endocrine Therapy Denosumab vs Placebo in ERPositive Breast Cancer Ellis G, et al. SABCS 2022. Abstract 47. Denosumab* 60 mg SC every 6 months (n = 127) Women with hormone receptor–positive breast cancer on adjuvant AI therapy (N = 252) Placebo* SC every 6 months (n = 125) Year 2 *Both arms given calcium 1000 mg daily and vitamin D ≥ 400 IU daily. Stratified by AI use: ≤ 6 months vs 6 months ? Phase III, randomized, doubleblind, placebo controlled trial ? Primary endpoint: % change in lumbar spine BMD from baseline to Month 12 – Measured using DEXA Early Breast Cancer: Endocrine Therapy Denosumab: Effec