title: Bisphosphonates and breast cancer incidence and recurrence.
abstract: 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.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. rchlebowski@gmail.com
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Nananda
authors.initials: N
authors.lastname: Col
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control; D004002:Clodronic Acid / Q000009:adverse effects / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid