What is the efficacy of bisphosphonate therapy for bone health management in primary breast cancer treatment?

Updated: Nov 06, 2019
  • Author: Winston W Tan, MD, FACP; Chief Editor: Marie Catherine Lee, MD, FACS  more...
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A growing body of evidence suggests that bisphosphonates may have antitumor activity. In a study of a first-generation bisphosphonate, clodronate, in patients with primary operable breast cancer, Powles et al reported a significant improvement in 5-year bone relapse–free survival. [12]

A 2008 study examined the potential role of bisphosphonates in cancer treatment–induced bone loss and found that aromatase inhibitors or androgen deprivation can be risk factors for osteopenia, osteoporosis, and bone fracture and that this risk can be mitigated with appropriate bisphosphonate therapy. [13]

In a study of anastrozole therapy for breast cancer, Markopoulos et al found that patients who had pretreatment osteopenia or osteoporosis received protection against bone loss if oral risedronate was added to their regimen. [14] However, patients with a normal bone mineral density before starting treatment were at very low risk for osteoporosis.

In two studies of breast cancer patients with tumor cells detected in bone marrow, zoledronic acid proved to be more effective than placebo in eliminating these cells. [15, 16]

A study by Coleman et al found that zoledronic acid is well tolerated in the adjuvant setting and can be safely administered along with adjuvant therapy, including chemotherapy, in women with stage II/III breast cancer. [17] A separate study by Hatoum et al found that zoledronic acid is associated with a lower risk and frequency of skeletal complications and a longer follow-up time. [18]

A randomized phase III trial (SWOG 0307) that compared zolendronic acid with two oral bisphosphonates (clodronate and ibandronate) in 6097 patients with stage I-III breast cancer receiving adjuvant systemic therapy found no evidence of difference in 3-year disease-free survival by type of bisphosphonate, either in the intent to treat analysis or based on age and menopausal status. Almost three quarters of patients indicated that they would prefer an oral versus an intravenous agent, if efficacy were equivalent. [19]

The Early Breast Cancer Trialists' Collaborative Group meta-analysis included 26 randomized trials involving 18,766 women with early breast cancer and compared 2 to 5 years of bisphosphonate therapy with no bisphosphonate therapy. [5] Overall, the reductions in recurrence, distant recurrence, and breast cancer mortality with bisphosphonate therapy were of borderline significance, although the reduction in bone recurrence was significant (RR, 0.83; P = 0.004). However, subsequent analysis revealed that although bisphosphonates had no benefit in premenopausal women, in postmenopausal women, bisphosphonates produced significant reductions in the following [5] :

  • Breast cancer recurrence (RR, 0.86;  P = 0.002)
  • Distant recurrence (RR, 0.82;  P = 0.0003)
  • Bone recurrence (RR, 0.72;  P = 0.0002)
  • Breast cancer mortality (RR, 0.82;  P = 0.002)

The findings were unaffected by bisphosphonate class, treatment schedule, estrogen-receptor status, nodes, tumor grade, or concomitant chemotherapy.

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