Breast Cancer, Bone Metastases, and Skeletal-related Events

Advancements in cancer therapies have extended patients´ lives and improved patients´ outcomes. Because patients are living longer, they are at increased risk for symptomatic bone disease, increasing the need for definitive and durable treatment.^1,2

In fact, it is estimated that 65% to 75% of patients with advanced breast cancer will eventually develop bone metastases throughout the course of their disease.³ However, data from a study of IV bisphosphonate use suggest that up to 54% of patients whose breast cancer has metastasized to the bone remain untreated for bone metastases.⁴

As anticancer therapies have extended overall survival, the likelihood that a patient with advanced cancer will live long enough to experience a skeletal-related event (SRE) is increasing.⁵ In clinical studies, SREs have prospectively been defined as pathologic bone fractures (vertebral or nonvertebral), spinal cord compression, surgery to bone, radiation therapy to bone (including the use of radioisotopes), and hypercalcemia of malignancy.^6-9

Examples of SREs

 

SREs in patients with bone metastases

One study conducted in 754 patients with breast cancer showed that 68% (263/384) of patients untreated for bone metastases experienced an SRE compared with 53% (194/367) of those receiving pamidronate (P < 0.001). The dose of pamidronate administered was 90 mg per intravenous infusion every 3 to 4 weeks for 24 cycles.¹⁰

Additionally, the same study showed that among untreated patients, the median time to the first SRE was 7 months compared with 12.7 months in patients who were treated (P < 0.001).¹⁰

Frequency of subsequent SREs

Patients with bone metastases often experience multiple SREs.^11,12 A study involving 1,122 patients with breast cancer or multiple myeloma treated with IV bisphosphonates showed that before study entry, 68% of patients (n = 760) had experienced at least 1 SRE. These patients had a 2-fold higher risk of developing an on-study SRE compared with patients who had not experienced an SRE (hazard ratio = 2.08).¹²

Read more about:

• Increased RANK Ligand signaling in patients with bone metastases
• Breast cancer treatment and bone loss
• Aromatase inhibitors: decreasing BMD and increasing fracture risk

References:

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71-96.
2. Papagelopoulos PJ, Savvidou OD, Galanis EC, et al. Advances and challenges in diagnosis and management of skeletal metastases. Orthopedics. 2006;29(7):609-622.
3. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80(8 suppl):1588-1594.
4. Mortimer JE, Schulman K, Kohles JD. Patterns of bisphosphonate use in the United States in the treatment of metastatic bone disease. Clin Breast Cancer. 2007;7:682-689.
5. Schulman KL, Kohles J. Economic burden of metastatic bone disease in the US. Cancer. 2007;109(11):2334-2342.
6. Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002;94(19):1458-1468.
7. Saad F, Gleason DM, Murray R, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004;96(11):879-882.
8. Saad F, Lipton A, Cook R, et al. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer. 2007;110:1860-1867.
9. Rosen LS, Gordon D, Kaminski M, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J. 2001;7:377-387.
10. Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000;88:1082-1090.
11. Kanis JA, Johnell O, De Laet C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone. 2004;35:375-382.
12. Kaminski M, Rosen L, Gordon D, et al. Zoledronic acid versus pamidronate in patients with breast cancer and multiple myeloma who are at high risk for skeletal complications. J Clin Onc. 2004;22(145):857.