Breast-Cancer Adjuvant Therapy with Zoledronic Acid

Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer

“…S2 and S3), is relevant clinically for the therapy of HER2-amplified breast cancers, and whether this interaction causes the reduced disseminated tumor cell burden noted in breast cancer patients treated with zoledronic acid (6)(7)(8). If such a benefit is proven, the use of bisphosphonates in a molecularly defined subgroup of HER2-amplified breast cancer patients, either alone or in combination with trastuzumab, may become a reality (19).…”

“…Knocking down the four HER isoforms abrogate bisphosphonate action, proving a selective action through this pathway (4). Indeed, this new action might explain the reduced disseminated tumor cell burden and increased disease-and recurrence-free survival documented in early breast cancer patients (5)(6)(7)(8). The process may also explain epidemiologic observations in which patients on oral bisphosphonates for their osteoporosis had a lower incidence of colon and breast cancer (9)(10)(11).…”

Bone remodeling markers and bone metastases: From cancer research to clinical implications

“…On the basis of the hypothesis that an increased bone metabolism may facilitate the development of BM, prior studies tested the added benefit of ZA in the adjuvant treatment of early breast cancer. A benefit in terms of relapse-free survival was found in premenopausal women under complete estrogen blockage (goserelin with either tamoxifen or anastrazol; ABCSG-12; Gnant et al 56 ), in postmenopausal women under aromatase inhibitors (letrozol; ZO-FAST; Coleman et al 57 ) and in women under systemic adjuvant therapy who had undergone menopause more than 5 years earlier (AZURE; Coleman et al 58 ). Moreover, an individual patient data meta-analysis condensing information from 41 randomized trials that compared bisphosphonates (BPs) with placebo or no BPs in patients with breast cancer (n ¼ 17 016, of which 10 540 were postmenopausal women) further demonstrated a 34% improvement in the rate of bone recurrences (Po0.001) and a novel 17% improvement in the rate of breast cancer death (P ¼ 0.004) in postmenopausal women treated with BPs.…”

Mechanisms of action of bisphosphonates in oncology: a scientific concept evolving from antiresorptive to anticancer activities

“…21 In this study, over 3000 pre-or postmenopausal women with stage II or III breast cancer were randomized to receive either standard therapy (mainly chemotherapy) or standard therapy with zoledronate for a duration of 5 years ( Table 1). A preplanned subgroup analysis of patients according to their menopausal status revealed, however, that the risk of disease progression in postmenopausal patients was reduced by 25% in the zoledronate group compared with the control group ( Table 1).…”

“…A preplanned subgroup analysis of patients according to their menopausal status revealed, however, that the risk of disease progression in postmenopausal patients was reduced by 25% in the zoledronate group compared with the control group ( Table 1). 21 The difference in disease recurrences according to menopausal status also translated into a survival benefit with postmenopausal patients showing a 26% reduction in the risk of death ( Table 1). 21 Interestingly, while using adjuvant clodronate (alongside standard therapy) in women with stage I-III endocrine-responsive breast cancer (NSABP B-34 trial; n ¼ 3323), Paterson et al 22 reported results similar to those obtained in the AZURE trial, showing no overall effect on disease-free survival in all patients but a significant reduction on disease progression in those older than 50 years ( Table 1).…”