Can Prolia (denosumab) be prescribed to a patient receiving letrozole for hormone‑receptor‑positive breast cancer?

Can You Get Prolia While Taking Letrozole?

Yes, Prolia (denosumab) can and should be prescribed to patients receiving letrozole for hormone receptor-positive breast cancer when they have low bone mineral density or are at risk for aromatase inhibitor-induced bone loss. This combination is well-established, safe, and specifically addresses a major side effect of aromatase inhibitor therapy.

Evidence Supporting Concurrent Use

Bone Protection During Aromatase Inhibitor Therapy

• Denosumab significantly increases bone mineral density in patients on aromatase inhibitors, with lumbar spine BMD increasing by 5.5% at 12 months and 7.6% at 24 months compared to placebo 1
• At 36 months, the longest reported treatment period, lumbar spine BMD increased by 8.8%, right femoral neck by 4.3%, and left femoral neck by 3.1% in breast cancer patients receiving adjuvant aromatase inhibitors with denosumab 2
• BMD increases occur as early as 1 month after starting denosumab and are not influenced by the duration of prior aromatase inhibitor therapy 1

Disease-Free Survival Benefit

• Beyond bone protection, denosumab may improve cancer outcomes: In the ABCSG-18 trial of 3,425 postmenopausal patients with hormone receptor-positive breast cancer on aromatase inhibitors, denosumab significantly improved disease-free survival (hazard ratio 0.82,95% CI 0.69-0.98, p=0.0260) 3
• Disease-free survival was 89.2% at 5 years and 80.6% at 8 years in the denosumab group versus 87.3% at 5 years and 77.5% at 8 years in placebo 3

Clinical Implementation

Indications for Denosumab with Letrozole

• Baseline bone mineral density assessment via DEXA scan is recommended before starting aromatase inhibitor therapy, particularly for patients at risk of osteoporosis 4
• Consider denosumab for patients with T-scores between -1.0 and -2.5 (osteopenia) or lower than -2.5 (osteoporosis) 4
• Patients with evidence of low bone mass (excluding frank osteoporosis at baseline) are appropriate candidates 1

Dosing and Monitoring

• Administer denosumab 60 mg subcutaneously every 6 months during aromatase inhibitor therapy 1, 3
• All patients should receive daily calcium and vitamin D supplementation (500 mg elemental calcium and at least 400 IU vitamin D) 4, 2
• Monitor BMD every 6 months to assess treatment response 2
• Bone turnover markers (urinary N-telopeptide) decrease as early as 1-3 months after denosumab initiation and predict BMD improvement 5

Safety Profile

Adverse Events

• The overall incidence of adverse events with denosumab is similar to placebo in breast cancer patients on aromatase inhibitors 1, 3
• Most common serious adverse events include osteoarthritis (3.6% vs 3.4% placebo), meniscus injury (1.3% vs 1.4%), and cataract (0.9% vs 1.7%) 3
• No independently adjudicated cases of osteonecrosis of the jaw or atypical femoral fractures were recorded in the ABCSG-18 trial 3
• Febrile neutropenia rates remain low when denosumab is combined with aromatase inhibitors 1

Important Caveats

• One treatment-related death (pneumonia, septic kidney failure, and cardiac decompensation) occurred in 3,425 patients treated with denosumab, representing a <0.1% risk 3
• No non-traumatic clinical fractures occurred in patients receiving both aromatase inhibitors and denosumab through 36 months of follow-up 2

Comparison with Other Bone-Directed Therapies

• Oral bisphosphonates and intravenous zoledronic acid also preserve BMD during aromatase inhibitor therapy 4
• Denosumab demonstrates superior BMD increases compared to historical bisphosphonate data, with consistent gains at both trabecular (spine) and cortical (hip, radius) bone sites 1
• The twice-yearly subcutaneous administration of denosumab may offer convenience advantages over more frequent oral bisphosphonates or annual intravenous zoledronic acid 4