Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer

Khan, Qamar J.; Reddy, Pavan S.; Kimler, Bruce F.; Sharma, Priyanka; Baxa, S.; O’Dea, Anne; Klemp, Jennifer R.; Fabian, Carol J.

doi:10.1007/s10549-009-0495-x

Cited by 172 publications

(156 citation statements)

References 28 publications

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“…In a previous study of women of different ethnicities starting letrozole, there was a prevalence of vitamin D deficiency of 18/60 and with only 13/60 with concentrations > 100nM [18]. In this study, which measured 25(OH)D using liquid chromatography with mass spectroscopy (LC/MS) , the threshold was approximately 165 nM (equivalent to 66 ng/ml) using disability from joint pain as the outcome.…”

Section: Ai-associated Joint Pain and Vitamin D Status At 3 Monthsmentioning

confidence: 80%

“…The mechanism for this association is unclear, It has been proposed [18] that the AI induced reduction in estrogen may unmask subclinical osteomalacia through the loss of estrogen mediated activation of 1alpha hydroxylase [35], the vitamin D receptor [36,37] and/or vitamin D binding protein. In addition, AI use may attenuate vitamin D metabolism through competition with the hepatic CYP3A4 system [18]. Conversely, the promoter region of the aromatase gene is also activated by vitamin D in a number of tissues [38] hence higher concentrations of vitamin D may attenuate local estrogen deficiency [39].…”

Section: Ai-associated Joint Pain and Vitamin D Status At 3 Monthsmentioning

confidence: 99%

“…Given the potential associations with adverse outcomes it is a concern that biochemical vitamin D insufficiency as defined by the concentration of serum 25OHD <30 ng/ml is being increasing recognized as common [15], with community rates of 67 to 87% in Barcelona, Spain [16,17]. In studies of women with breast cancer, 30% had concentrations of less than <20 ng/ml, and this was in part dependent on the season the sample was taken [18]. The prevalence of vitamin D deficiency among postmenopausal women diagnosed with early breast cancer and candidates for AI treatment in our hospital has been reported elsewhere [19]: 88.1% of them had serum 25(OH)D concentrations <30 ng/ml, and 21.2% had serum 25(OH)D <10ng/ml.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study

Prieto-Alhambra

Javaid

Servitja

et al. 2010

Breast Cancer Res Treat

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Purpose: Aromatase inhibitor (AI) associated arthralgia limits adherence to therapy in breast cancer. The pathophysiology may involve vitamin D status. We wished to establish the optimal concentration of 25(OH)D that prevents or minimizes arthralgia. Methods:We used a prospective cohort of 290 women starting AI in whom baseline vitamin D was measured. All received daily vitamin D3 (800 IU) with calcium. Women with baseline 25(OH)D concentration <30 ng/ml also received 16,000 IU of D3 orally every two weeks. The primary outcome was incident or worsening joint pain derived from baseline and three month VAS for joint pain. Regression models were used to analyse the association between vitamin D concentrations at 3 months and pain adjusting for age, BMI, season when the sample was drawn, aromatase inhibitor (exemestane vs letrozole/anastrozole), prior tamoxifen therapy, baseline NTX, and previous fracture.Results: 90% of women had a 25(OH)D <30 ng/ml at baseline. After supplementation (daily 800 IU and additional additional 16,000 IU every two week), 50% of them still failed to reach adequate concentrations at three months. In the whole cohort, there was an increase in joint pain (mean 1.16 points SD 2.66; p<0.001) and the increase was significantly (p= 0.02) attenuated in those that reached concentrations of 25(OH)D of ≥40 ng/ml, with a lower risk of incident arthralgia (OR 0.12 ** [0.03 to 0.40]).Conclusion: A target concentration of 40ng/ml 25OHD may prevent development of AI arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline.

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Section: Ai-associated Joint Pain and Vitamin D Status At 3 Monthsmentioning

confidence: 80%

Section: Ai-associated Joint Pain and Vitamin D Status At 3 Monthsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study

Prieto-Alhambra

Javaid

Servitja

et al. 2010

Breast Cancer Res Treat

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“…Consequently, recent studies have reported that daily vitamin D supplements may have a protective effect on pathogenesis (Khan et al 2010, Rastelli et al 2011. This observation may represent a promising possibility for maintaining quality of life and for preventing discontinuation of a potentially life-saving adjuvant anticancer treatment.…”

Section: Musculoskeletal Symptomsmentioning

confidence: 99%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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Breast cancer is the most prevalent type of cancer in women and responsible for significant female cancer-related mortality worldwide. In the Western world, over 80% of breast cancers are hormone-receptor positive for which endocrine therapy is administered. The main anti-estrogen treatments in use consist of selective estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review, the focus will lie on exemestane, its clinical use, and its side-effect profile. Exemestane is the only third-generation steroidal AI. Its efficacy as a first-line treatment in metastatic breast cancer has been demonstrated. Therefore, exemestane could be considered a valid first-line therapeutic option, but it also can be used in second-line or further situations. Exemestane is mostly used as part of sequential adjuvant treatment following tamoxifen, but in this setting it is also active in monotherapy. Furthermore, this AI has been studied in the neoadjuvant setting as presurgical treatment, and even as chemoprevention in high-risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such as endometrial changes and thromboembolic disease but may also cause some inconvenient side effects itself. Additionally, there is a lack of total crossresistance between exemestane and nonsteroidal AIs as far as their anti-tumoral efficacy is concerned; moreover the two classes of AIs display a nontotal overlapping toxicity profile. Taking together, exemestane can be considered as a useful treatment option at all stages of breast cancer.

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“…After 16 weeks of letrozole, the absence of joint disability was reported in more women with 25-OHD levels above rather than below 66 ng/ml (52 vs. 19%, P = 0.026). This suggests that there may be a role of vitamin D, although a limitation of this study was that it was not randomised and there was no placebo control [66].…”

Section: Intervention Studiesmentioning

confidence: 99%

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

Din

Dodwell

Wakefield

et al. 2010

Breast Cancer Res Treat

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Aromatase inhibitors (AIs) are a standard of care for the adjuvant treatment of hormone responsive early carcinoma of the breast as demonstrated in a number of large international phase III randomised trials. Arthralgia was a somewhat unexpected side effect of this class of agents and has proven to be potentially problematic in clinical practice. Although rates of up 35% have been reported in the randomised trials, the figure has been much higher in subsequent case series. There is concern that these symptoms are significant and may affect compliance and thus the overall efficacy of treatment. It is therefore extremely important that we evaluate this syndrome with a view to gaining more information regarding its clinical features and possible aetiological mechanism. The potential aetiological mechanisms and evidence for aromatase inhibitor-induced arthralgia (AIA) are reviewed in this article. Looking forward, it is now important that prospective clinical trials are well designed to evaluate this syndrome and potential therapeutic strategies to circumvent it. Radiological imaging and biochemical analyses may help our understanding of AIA and these are discussed.

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Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer

Cited by 172 publications

References 28 publications

Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study

Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

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

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