Effect of Anastrozole on Bone Mineral Density: 5-Year Results From the Anastrozole, Tamoxifen, Alone or in Combination Trial 18233230

Eastell, Richard; Adams, Judith E.; Coleman, Robert E.; Howell, Anthony; Hannon, Rosemary A.; Cuzick, Jack; Mackey, John R.; Beckmann, Matthias W.; Clack, Glen

doi:10.1200/jco.2007.11.0726

Cited by 369 publications

(240 citation statements)

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“…In postmenopausal women with recently diagnosed early breast cancer, the use of an aromatase inhibitor in the adjuvant setting has been associated with an average bone loss of around 2% per year in the LS and 1.5% at the hip [9][10][11][12]. In IES, we have previously reported that significant changes in BTM and BMD appeared within 6m of switching from tamoxifen to exemestane [9].…”

Section: Discussionmentioning

confidence: 99%

Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study

Coleman

Banks

Girgis

et al. 2010

Breast Cancer Res Treat

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The adjuvant use of aromatase inhibitors in breast cancer is associated with adverse effects on bone health. We previously reported a decline in bone mineral density (BMD) following the switch from tamoxifen to exemestane in the Intergroup Exemestane Study (IES). Here we report effects of endocrine treatment withdrawal on BMD, bone turnover markers (BTM) and fracture rates.4724 patients took part in IES, and 206 patients were included in a bone substudy. BMD and BTM were assessed pre-randomization, during, and after the end of treatment (EOT). To evaluate treatment withdrawal effects, 12 and 24 month (m) post-EOT BMD results are available for 122 and 126 patients respectively. Similar patient numbers had BTM measured post EOT.Following treatment withdrawal, the differences in BMD observed between the two endocrine strategies were partially reversed. At 24m from EOT, spine BMD increased by 1.53% (95% CI 0.63 to 2.43; p=0.001) after stopping exemestane, and fell by 1.93% (95% CI -2.91 to 0.95; p=0.0002) following tamoxifen withdrawal. A similar pattern of changes was observed at the hip. At 2 years post EOT, BMD changes from baseline were similar with both treatment strategies.Corresponding inverse changes in BTM were seen, with an increase following tamoxifen withdrawal and a reduction after exemestane. A higher number of fractures occured during exemestane treatment, but fracture rates were similar after treatment withdrawal.With the switch strategy used in IES, the on treatment adverse bone effects of exemestane are reversed. Ongoing monitoring of BMD is therefore not routinely required. Word count: 249Reversal of skeletal effects of endocrine treatments in the IES 3

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Section: Discussionmentioning

confidence: 99%

Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study

Coleman

Banks

Girgis

et al. 2010

Breast Cancer Res Treat

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“…Furthermore, because BMD measurement occurred within a short time from BC diagnosis (B15 days) in this study, bone loss that would occur during BC treatment is not considered. For example, AIBL and ovarian suppression-associated bone loss are most severe within the first 3 years of beginning therapy, but remain elevated for the duration of therapy (Howell et al, 2005;Thurlimann et al, 2005;Coombes et al, 2007;Eastell et al, 2008;Gnant et al, 2008). Therefore, patients are likely to experience additional decreases in BMD during BC treatment, making the management of bone health an increasing concern.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to natural bone loss associated with ageing, therapies for BC can impair bone health directly, or indirectly by disrupting estrogen production and signalling (Pfeilschifter and Diel, 2000). For example, ovarian suppression using agents such as goserelin in premenopausal women, or aromatase inhibitor (AI) therapy in postmenopausal women, can result in substantial bone loss (Eastell et al, 2008;Gnant et al, 2008). Adjuvant AI therapy is now the standard of care for postmenopausal women with HR þ BC because of its superior disease-free survival results and more favourable side-effect profile (particularly with regard to venous thrombosis and endometrial cancers) compared with tamoxifen (Howell et al, 2005;Thurlimann et al, 2005;Coombes et al, 2007).…”

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confidence: 99%

“…However, AIs vary in their ability to suppress estrogen levels in vivo (Geisler et al, 2008), and recent clinical trial data indicate that the near-complete estrogen suppression associated with letrozole treatment may further improve overall survival vs tamoxifen in postmenopausal women with HR þ BC (Mouridsen et al, 2009). Overall, the profound estrogen depletion achieved with AI therapy is associated with decreased BMD and increased fracture risk (Coombes et al, 2004;Howell et al, 2005;Thurlimann et al, 2005;Eastell et al, 2008). Cytotoxic chemotherapy can also impair bone health either directly, through effects on bone (e.g., methotrexate), or indirectly, through premature ovarian failure (Pfeilschifter and Diel, 2000;Shapiro et al, 2001).…”

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confidence: 99%

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Assessment of fracture risk in women with breast cancer using current vs emerging guidelines

et al. 2010

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BACKGROUND: Breast cancer (BC) therapies can have negative effects on bone. Current guidelines recommend antiresorptive therapy based on bone mineral density (BMD), and emerging guidelines include both clinical risk factors and BMD to assess the overall fracture risk. A retrospective, case -controlled study based on current and emerging guidelines was conducted in women with newly diagnosed BC to identify those who were at increased fracture risk based on current and emerging guidelines. METHODS: Baseline characteristics, fracture risk factors, and lumbar -spine (LS) and total-hip BMD in women with BC (88 premenopausal and 402 postmenopausal) were assessed to determine who would receive bisphosphonate therapy based on current and emerging guidelines. RESULTS: Among patients with estrogen-receptor-positive (ER þ ) BC, 18.8% of premenopausal and 36.9% of postmenopausal women were osteopenic at LS. In the postmenopausal cohort, osteoporosis was more prevalent in patients with ER þ vs ER -BC. Current guidelines identified 8.9% of patients as eligible for antiresorptive therapy, clinical risk factors alone identified 6.5%, and BMD plus clinical risk factors identified 28.6%. CONCLUSIONS: In addition to fracture risk factors present at BC diagnosis, cancer therapies leading to BMD loss further increase fracture risk. Evaluating both BMD and clinical risk factors may allow more effective identification of BC patients with elevated fracture risk.

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“…In a study among women with breast cancer, anastrozole was associated with decreased bone mineral density after 5 years of treatment [41]. Letrozole may be preferred because it does not cause hypoestrogenemia and its related adverse effects, perhaps because the small dose of letrozole used in our study (2.5 mg) is insufficient to inhibit the production of estradiol in the ovaries [40••].…”

Section: Aromatase Inhibitorsmentioning

confidence: 99%

Medical Management of Uterine Fibroids

Parsanezhad

Jahromi

2012

Curr Obstet Gynecol Rep

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Uterine leiomyomas are the most common benign tumors of the uterus. Though benign, they can affect the quality of life for many women. Compared with the standard surgical treatments, medical therapy is attractive and avoids possible surgery-related complications. No medical therapy currently exists that can induce rapid regression of the myoma and symptoms with minimal side effects without affecting fertility. This review evaluates medical treatments that are currently available for the treatment of uterine fibroids.

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Effect of Anastrozole on Bone Mineral Density: 5-Year Results From the Anastrozole, Tamoxifen, Alone or in Combination Trial 18233230

Cited by 369 publications

References 29 publications

Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study

Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study

Assessment of fracture risk in women with breast cancer using current vs emerging guidelines

Medical Management of Uterine Fibroids

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