From the Guidelines
Letrozole can be used for metastatic breast cancer in patients with osteoporosis, but requires careful management of bone health. For hormone receptor-positive metastatic breast cancer, the standard letrozole dose is 2.5 mg orally once daily, continued until disease progression or intolerable toxicity. In patients with osteoporosis, concurrent bone-protective therapy is essential, typically with bisphosphonates (such as zoledronic acid 4 mg IV every 3-6 months or oral alendronate 70 mg weekly) or denosumab (60 mg subcutaneously every 6 months) 1. Calcium supplementation (1000-1200 mg daily) and vitamin D (800-1000 IU daily) should also be prescribed. Regular bone mineral density monitoring every 1-2 years is recommended. This approach is necessary because aromatase inhibitors like letrozole reduce estrogen levels, which can accelerate bone loss and increase fracture risk. The benefits of letrozole in controlling hormone-sensitive breast cancer often outweigh these risks when appropriate bone-protective measures are implemented, as supported by recent guidelines 1. Patients should also be counseled about weight-bearing exercise and fall prevention strategies to further protect bone health. It is also important to note that the use of bisphosphonates should be accompanied by calcium and vitamin D supplementation, and the optimal dosing of bisphosphonates is every 12 weeks 1. Overall, the management of bone health is crucial in patients with metastatic breast cancer and osteoporosis, and letrozole can be a viable treatment option when used in conjunction with bone-protective therapies.
From the FDA Drug Label
- 1 Bone Effects Use of letrozole may cause decreases in bone mineral density (BMD). Consideration should be given to monitoring BMD. Based on a median follow-up of patients for 28 months, the incidence of clinical fractures from the core randomized study in patients who received letrozole was 5.9% (152) and placebo was 5.5% (142). The incidence of self-reported osteoporosis was higher in patients who received letrozole 6.9% (176) than in patients who received placebo 5.5% (141). During treatment or within 30 days of stopping treatment (median duration of treatment 60 months) a higher rate of fractures was observed for letrozole (10.4%) compared to placebo (5.8%), as also a higher rate of osteoporosis (letrozole 12.2% vs placebo 6. 4%).
- Letrozole may exacerbate osteoporosis: The FDA drug label warns that letrozole may cause decreases in bone mineral density (BMD) and that the incidence of clinical fractures and self-reported osteoporosis is higher in patients receiving letrozole compared to placebo.
- Monitoring BMD is recommended: Consideration should be given to monitoring BMD in patients receiving letrozole, especially those with pre-existing osteoporosis.
- Use with caution in patients with osteoporosis: Letrozole can be used in patients with metastatic breast cancer who have osteoporosis, but it is recommended to use it with caution and to monitor BMD regularly 2 2.
From the Research
Letrozole Administration in Metastatic Breast Cancer Patients with Osteoporosis
- Letrozole can be given to patients with metastatic breast cancer who have osteoporosis, but it is essential to consider the potential risk of further bone loss 3, 4, 5.
- Studies have shown that zoledronic acid, a bisphosphonate, can prevent bone loss in postmenopausal women with osteoporosis or osteopenia who are starting letrozole therapy 3, 4, 5.
- Zoledronic acid has been found to increase bone mineral density (BMD) at the lumbar spine and femoral neck, reducing the risk of fractures in these patients 3, 4, 5.
- The use of bisphosphonates, such as zoledronic acid, is recommended for patients with a high risk of fracture, including those with a T-score ≤-2 or two or more clinical risk factors 6.
Management of Osteoporosis in Breast Cancer Patients
- A careful baseline evaluation of the risk of fracture is necessary for postmenopausal women about to start treatment with aromatase inhibitors, including letrozole 6.
- Bisphosphonates, such as zoledronic acid, and denosumab, an anti-RANK ligand antibody, are emerging as therapeutic options to prevent AI-induced bone loss and reduce the risk of fractures 6.
- The optimal regimen for long-term zoledronic acid therapy has not been defined, but continuing therapy for more than 2 years may extend its beneficial effect 7.