Bisphosphonates are commonly used in patients with
breast cancer to reduce skeletal-related events in metastatic disease and to mitigate bone loss associated with adjuvant
therapy. Preclinical studies have shown that
bisphosphonates may directly inhibit
breast cancer cell proliferation and
metastasis. Clinical trials evaluating the oral
bisphosphonate clodronate as a component of adjuvant
therapy identified a potential reduction in
cancer recurrence. Subsequently, trials of
zoledronic acid have demonstrated prolonged disease-free survival in postmenopausal or otherwise
estrogen-depleted women with early
breast cancer. In the ABCSG-12 trial, the addition of twice-yearly
zoledronic acid (4 mg IV) to adjuvant endocrine
therapy improved disease-free survival in premenopausal women undergoing ovarian suppression. Similar results were observed in postmenopausal women receiving
aromatase inhibitors in the ZO-FAST trial, and in women who were at least 5 years past menopause in the AZURE trial. Four recent observational studies (2 cohort studies and 2 case-control analyses) generally support an association between oral
bisphosphonate use and lower
breast cancer incidence. Ongoing
breast cancer adjuvant clinical trials are further evaluating
bisphosphonates and, by their influence on contralateral
cancers, may provide more evidence regarding the potential of
bisphosphonates for
breast cancer prevention.