Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know and how can we find out more?

Din, Omar; Dodwell, David; Wakefield, Richard J.; Coleman, Robert E.

doi:10.1007/s10549-010-0757-7

Cited by 68 publications

(57 citation statements)

References 89 publications

(95 reference statements)

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“…However, through their ability to profoundly suppress circulating and tissue based estrogens, AI are associated with musculoskeletal adverse events. These include arthralgia and accelerated bone loss which may lead to fragility fractures [5,6].…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…However, more recent studies of women receiving ais as adjuvant treatment have reported rates of 47% 8 and as high as 61% 16 . Regardless of the incidence, it is clear that ai treatment is associated with a degree of arthralgia requiring medical attention, and this aspect of ai treatment is being evaluated in a number of ongoing studies 3 . In our study, awareness that all women had msk conditions at baseline and regular monitoring of pain symptoms made it possible to keep the symptoms under control.…”

Section: Discussionmentioning

confidence: 99%

“…Slightly higher levels of 1,25(OH) 2 vitamin D 3 were observed at baseline in patients with pain increase, but did not significantly change during treatment; however, average levels of 25(OH) vitamin D 3 increased, likely because of supplementation. Although biochemical markers did not discriminate efficiently between pain groups, a signature of 166 genes in peripheral blood mononuclear cells was identified that could stratify patients into the various groups observed in this pilot study.…”

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confidence: 84%

“…The incidence of musculoskeletal (msk) symptoms in phase iii clinical trials of anastrozole, letrozole, and exemestane has been recently reviewed 3 , and women on those ais have shown significantly higher rates of arthralgia than are seen with tamoxifen ( Table i). In a specific study investigating arthralgia in 200 patients on ais, 47% of patients reported ai-related joint pain, and 44% reported stiffness 8 .…”

Section: Introductionmentioning

confidence: 99%

“…Here, we explored the potential of gene expression profiling studies in pbmcs to stratify patients according to pain groups; our aim was to assess the potential value of profiling as a predictor of arthralgia risk. It has been proposed that women who develop ai-related arthralgia may have an anergic cytokine phenotype with lower baseline levels of some interleukins and colony-stimulating factors 3 . Furthermore, to accurately determine the effect of pain on patient compliance, we measured serum estradiol levels as an indicator of patient adherence to ai treatment.…”

Section: Introductionmentioning

confidence: 99%

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A Prospective Pilot Study Investigating the Musculoskeletal Pain in Postmenopausal Breast Cancer Patients Receiving Aromatase Inhibitor Therapy

et al. 2011

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Background: Although arthralgia is a known adverse effect of aromatase inhibitor (ai) treatment in postmenopausal breast cancer patients, few studies have carried out a comprehensive evaluation of the nature, onset, and incidence of musculoskeletal (msk) pain in these patients. We therefore used a pilot study to identify conditions or markers predictive of pain. Methods: For 24 weeks, we monitored 30 eligible postmenopausal women starting ai therapy. Pre-existing and incident msk conditions and pain were assessed clinically and with ultrasonography of the hands and wrists. In addition, patient questionnaires were used to assess pain before and during ai therapy. Biochemical markers were measured at baseline and at regular intervals after anastrozole therapy began. Gene profiling studies were carried out before and 48 h after the initial ai administration. Results: Over the 24-week study period, 20 participants (67%) showed no pain symptoms; 5 (17%) experienced low or moderate pain at baseline, which did not increase with ai treatment; and during therapy, 5 (17%) showed exacerbation of pain attributable to osteoarthritis of the hand and to finger flexor tenosynovitis. Although all 30 participants had some degree of msk conditions before anastrozole therapy started, the pre-existing conditions did not necessarily predispose the women to increased pain during anastrozole treatment. Higher levels of urinary N-telopeptides of type i collagen were associated with the groups presenting pain, suggesting a higher extent of pre-existing bone resorption, without significant evolution over the 24-week treatment period. Slightly higher levels of 1,25(OH)2 vitamin D3 were observed at baseline in patients with pain increase, but did not significantly change during treatment; however, average levels of 25(OH) vitamin D3 increased, likely because of supplementation. Although biochemical markers did not discriminate efficiently between pain groups, a signature of 166 genes in peripheral blood mononuclear cells was identified that could stratify patients into the various groups observed in this pilot study. The gene signature was enriched in components of inflammatory signalling and chemokine expression, of antitumoural immunity pathways, and of metabolic response to hormones and xenobiotics, although no clinically significant association could be made in the present study, considering the small number of patients. Nevertheless, the observed trend suggests the feasibility of developing surrogate predictive markers of msk pain. Patient compliance was high in this study and was not affected by pain exacerbation. Conclusions: Baseline msk assessment showed pre-existing causes for pain in most of the study patients before initiation of the ai. Exacerbation of existing osteoarthritis pain and tenosynovial symptoms was the primary cause of pain increase. Musculoskeletal pain assessment at baseline and prompt treatment of pain symptoms may help to optimize adherence to ai therapy. The value of routinely assessing inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate was not supported by our pilot study. Gene expression profiles in peripheral blood mononuclear cells may be further explored in larger-scale studies as stratification markers to identify patients at risk of developing arthralgia.

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Light‐intensity and moderate‐to‐vigorous intensity physical activity among older adult breast cancer survivors with obesity: A narrative review

et al. 2022

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Background With an aging population, rising incidence of breast cancer, improved survival rates, and obesity epidemic, there will be a growing population of older adult breast cancer survivors with obesity. This complex population, often with multimorbidity, is at risk for several poor health outcomes, including recurrence, cardiovascular disease, dementia, and diabetes, and a number of deleterious symptoms, including a worsened inflammatory profile, breast cancer‐ related lymphedema, mobility disability, cognitive impairment, anxiety, and depressive symptoms. A wealth of meta‐analytic and randomized controlled trial evidence show that adherence to World Health Organization and 2018 United States Physical Activity guidelines‐based levels of moderate‐to‐vigorous physical activity (MVPA) reduces risk of all‐cause mortality, and improves symptoms. However, few survivors engage in recommended levels of MVPA, and symptoms related to their multimorbidity may preclude engaging in sufficient levels of MVPA. Additional research of MVPA in this population is warranted; however, understudied light‐intensity physical activity (LIPA) may be a more pragmatic target than MVPA among this complex population facing extensive challenges meeting MVPA recommendations. Large benefits are likely to occur from increasing these survivors' total activity, and LIPA prescriptions may be a more pragmatic approach than MVPA to aid this transition. Methods We present a broad, narrative review of the evidence for MVPA and LIPA in this population on an array of health outcomes across the translational science spectrum (clinical, implementation, and public health), and identify a number of directions for future research focused on understanding the potential diverse health effects of LIPA. Conclusion Additional LIPA research is warranted, as LIPA prescriptions may be a pragmatic strategy to effectively promote physical activity to this complex population.

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Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know and how can we find out more?

Cited by 68 publications

References 89 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 Prospective Pilot Study Investigating the Musculoskeletal Pain in Postmenopausal Breast Cancer Patients Receiving Aromatase Inhibitor Therapy

Light‐intensity and moderate‐to‐vigorous intensity physical activity among older adult breast cancer survivors with obesity: A narrative review

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