Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.8 (FAST)
 758 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevention of cancer-treatment-induced bone loss (CTIBL) in long-term adjuvant breast cancer therapy is a high priority. Postmenopausal women with cancer, already at increased risk of bone loss because of age-related estrogen deficiency, face accelerated bone loss with the use of estrogen-depleting therapies such as third-generation aromatase inhibitors (AIs). Although effective in reducing cancer recurrence rates in the adjuvant setting, AIs are associated with bone loss and an increased risk of fractures. Bisphosphonates, which act by inhibiting osteoclastic bone resorption, have been shown to increase bone mineral density (BMD) and reduce fracture risk in postmenopausal women with established osteoporosis. Furthermore, the potent bisphosphonate zoledronic acid has been shown to be efficacious in reducing bone loss in premenopausal women receiving combination adjuvant hormone therapy (goserelin, a gonadotropin-releasing hormone agonist, plus either an AI or tamoxifen). The use of zoledronic acid to prevent CTIBL in postmenopausal women receiving adjuvant AI therapy with letrozole is currently being investigated in the Zometa/Femara Adjuvant Synergy Trial (Z-FAST). Postmenopausal women with stage I-IIIa estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer starting letrozole are randomized to receive either upfront zoledronic acid or delayed zoledronic acid. At 6 months, assessable women in the upfront group showed a mean increase of 1.55% in lumbar spine (L1 - L4) BMD, compared with a mean decrease of 1.78% in women in the delayed group, resulting in a difference of 3.33% between groups; moreover, women in the former group showed a mean increase of 1.02% in total hip BMD, compared with a mean decrease of 1.40% in those in the latter group, resulting in a significant difference of 2.42% between groups (P <.001). Thus, the Z-FAST BMD results show that upfront zoledronic acid prevents CTIBL in postmenopausal women receiving adjuvant letrozole therapy for early breast cancer. Combining the anticancer efficacy of letrozole with the bone-protective effect of zoledronic acid may be a successful treatment in this setting.
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PMID:Management of cancer-treatment-induced bone loss in postmenopausal women undergoing adjuvant breast cancer therapy: a Z-FAST update. 1673 Feb 72

Bisphosphonates are commonly used in patients with breast cancer to reduce skeletal-related events in metastatic disease and to mitigate bone loss associated with cancer therapy in early stage disease. In addition, adjuvant breast cancer trials evaluating the oral bisphosphonate clodronate suggested a reduction in cancer recurrence, but the findings were mixed, with 2 positive and 1 negative report. In the Austrian Breast and Colorectal Cancer Study Group (ABCSG) 12 study, adding the intravenous bisphosphonate zoledronic acid to endocrine therapy in premenopausal breast cancer patients significantly prolonged disease-free survival versus endocrine therapy alone (hazard ratio = 0.68; p = 0.008) at 62 months, and reduced local, regional, and distant recurrences. Clinical trial findings from other adjuvant trials (Z-FAST, ZO-FAST), neoadjuvant studies, and studies involving disseminated tumor cells (DTCs) are generally supportive of the ABCSG-12 conclusion, and recent data from AZURE suggest the importance of menopausal status. Preclinical studies provide data on the mechanisms of action that could mediate bisphosphonate direct and indirect anti-cancer effects. Recently, several observational studies (2 cohort studies and 2 case-control analyses) have associated oral bisphosphonate use with a lower breast cancer incidence. Such reports require cautious interpretation because confounding by indication is an issue: bisphosphonates are prescribed for women with low bone mineral density, and women with low bone density are at decreased breast cancer risk.
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PMID:Bisphosphonates and breast cancer prevention. 2186 27

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.
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PMID:Bisphosphonates and breast cancer incidence and recurrence. 2214 60