Guidance for the management of breast cancer treatment-induced bone loss: A consensus position statement from a UK Expert Group

Reid, David M.; Doughty, Julie; Eastell, Richard; Heys, Steven Darryll; Howell, Anthony; McCloskey, Eugène; Powles, Trevor J.; Selby, Peter; Coleman, Robert E.

doi:10.1016/j.ctrv.2008.03.007

Cited by 216 publications

(169 citation statements)

References 75 publications

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“…In terms of monitoring patients receiving tamoxifen followed by exemestane, we would recommend a BMD assessment around the time of switching endocrine treatment along with life-style advice to maximize bone health, ensure adequate intake of calcium and vitamin D, and follow a risk-adapted strategy for monitoring and intervention with bisphosphonates in line with current clinical guidelines [13,14]. Consistent with other reports, vitamin D levels were deficient or insufficient in the majority of patients [15].…”

Section: Discussionsupporting

confidence: 62%

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: Discussionsupporting

confidence: 62%

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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“…There is therefore unlikely to be any difference between these drugs in fracture rate or the rate of osteoporosis. In postmenopausal women, AI therapy has been associated with increases in bone turnover and bone loss at an average rate of 1 to 3% per year [14]. Consequently, an increase in fracture incidence is also observed when compared with that seen during tamoxifen use [14].…”

Section: Discussionmentioning

confidence: 99%

“…In postmenopausal women, AI therapy has been associated with increases in bone turnover and bone loss at an average rate of 1 to 3% per year [14]. Consequently, an increase in fracture incidence is also observed when compared with that seen during tamoxifen use [14]. In the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial, the fracture rate for anastrozole was 11% at a median followup of 68 months, versus 7.7% for tamoxifen [1].…”

Section: Discussionmentioning

confidence: 99%

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

McCaig

Renshaw

Williams

et al. 2009

Breast Cancer Res Treat

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International audienceALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-four patients were randomized to receive either 12 weeks of letrozole (2.5 mg; = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg; = 42) followed by 12 weeks of letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to tamoxifen ( = 38) or continued on anastrozole or letrozole. In the beginning of the study, 42 patients had taken tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior tamoxifen therapy resulted in a significantly lower mean baseline procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior tamoxifen had significantly greater increases than patients with no prior tamoxifen. Patients treated with 3 months of tamoxifen following 6 months of an AI showed a significant decrease in markers of bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time. Anastrozole and letrozole produce similar effects on bone metabolism and turnover. Stopping tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naïve patients. Patients given tamoxifen following AI therapy showed a decrease in markers of bone resorption

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“…Guidance from expert groups for premenopausal women with BC has been published and recommend that all premenopausal women be informed about the potential risk of bone loss prior to beginning anticancer therapy with the use of antiresorptives if the BMD Z-score is below À 2. 19,34 The first guidelines for the prevention and treatment of AIBL in postmenopausal women with BC, including clinical risk factors ± BMD, emerged in 2008. 34 On the basis of a systematic literature search, an expert group drafted a practical approach for the management of AIBL.…”

Section: Management Of Aibl/ctibl In Clinical Practicementioning

confidence: 99%

Cancer Treatment-Induced Bone Loss in women with breast cancer

Hadji

2015

BoneKEy Reports

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Osteoporosis is one of the most frequent diseases in postmenopausal women, leading to an increased fracture risk due to the physiologic loss of the bone protective effects of estrogen. Hereby, several risk factors for fracture such as prevalent fracture, low bone mineral density (BMD), age, low body mass index, family history, tendency to falls, smoking, use of SSRIs, glucocorticoid use etc. have been identified. In addition, the further reduction in endogenous estrogens with chemotherapy (CHT), GnRH analoga or aromatase inhibitors (AIs) continuously increases fracture risk. Breast cancer (BC) on the other hand is the most frequent cancer type in women. Recent reports indicate a continuous increased incidence, whereas mortality, due to early diagnosis and treatment improvements, is decreasing. Dependent on specific tumor characteristics, radiation, CHT, antibody treatment as well as endocrine treatment have been included into the adjuvant clinical treatment setting. Some but not all of these cancer-specific treatments interfere with bone turnover, leading to an accelerated bone loss referred to as cancer treatment-induced bone loss (CTIBL). Whereas CHT leads to an unspecific increase in bone resorption, AI reduces residual serum endogenous estrogen level and is associated with a decrease in BMD and increased fracture risk. Independent of the type of AI administered, bone loss is 2-3-fold increased compared with healthy, age-matched postmenopausal controls. Therefore, several guidelines have emerged to help managing CTIBL in women with BC including strategies to identify and treat those at highest risk for fractures. This review summarizes the current knowledge on CTIBL and fracturing risk and indicates preventative strategies.

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Guidance for the management of breast cancer treatment-induced bone loss: A consensus position statement from a UK Expert Group

Cited by 216 publications

References 75 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

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

Cancer Treatment-Induced Bone Loss in women with breast cancer

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