Musculoskeletal Adverse Events Associated with Adjuvant Aromatase Inhibitors

Khan, Qamar J.; O’Dea, Anne; Sharma, Priyanka

doi:10.1155/2010/654348

Cited by 38 publications

(37 citation statements)

References 46 publications

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“…Arthralgias affect a significant proportion of breast cancer patients and represent one of the leading reasons for the discontinuation of aromatase inhibitor therapy. [51, 52] High-dose vitamin D supplementation in breast cancer patients significantly reduces aromatase inhibitor-induced arthralgia. [37, 45] Falls, usually caused by a loss in balance associated with a decrease in muscular strength, are a major cause of excess morbidity and mortality.…”

Section: Discussionmentioning

confidence: 99%

The Association Between Breast Cancer Prognostic Indicators and Serum 25-OH Vitamin D Levels

et al. 2012

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Purpose Vitamin D deficiency in patients treated for breast cancer is associated with numerous adverse effects (bone loss, arthralgia, and falls). The first aim of this study was to assess vitamin D status, determined by 25-OH vitamin D levels, among women diagnosed with breast cancer according to demographic/clinical variables and bone mineral density (BMD). The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels. Methods This retrospective study included 224 women diagnosed with Stage 0-III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center. Total 25-OH vitamin D levels (D2 + D3) were determined at baseline for all participants. Vitamin D deficiency was defined as a 25-OH vitamin D level < 20 ng/mL, insufficiency as 20-31 ng/mL, and sufficiency as ≥ 32 ng/mL. BMD was assessed during the period between 3 months prior to and 6 months following the baseline vitamin D assessment. Based on the participants’ baseline levels, they received either no supplementation, low-dose supplementation (1,000 IU/day), or high-dose supplementation (≥ 50,000 IU/week), and 25-OH vitamin D was reassessed in the following 8-16 weeks. Results Approx 66.5% had deficient/insufficient vitamin D levels at baseline. Deficiency/insufficiency was more common among non-Caucasians, women with later-stage disease, and those who had previously received radiation therapy (p<0.05). Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD (p=0.03). Compared to the no supplementation group, weekly high-dose supplementation significantly increased 25-OH vitamin D levels, while daily low-dose supplementation did not significantly increase levels. Conclusions Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine. Clinicians should carefully consider vitamin D supplementation regimens when treating vitamin D deficiency/insufficiency in breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

The Association Between Breast Cancer Prognostic Indicators and Serum 25-OH Vitamin D Levels

et al. 2012

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“…Further, about a third of women in clinical trials who are treated with AIs suffer from joint pain (arthralgias) and muscle pain (myalgias) [3] that may affect quality of life as well as treatment adherence. The reason for these musculoskeletal symptoms is uncertain but is often attributed to the estrogen depletion [6]. However, all women treated with AIs have low estrogen levels and only a subset of these women develop symptoms [7].…”

Section: Introductionmentioning

confidence: 99%

Androgens and musculoskeletal symptoms among breast cancer patients on aromatase inhibitor therapy

Gallicchio

MacDonald

Wood

et al. 2011

Breast Cancer Res Treat

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Aromatase inhibitors (AIs), the adjuvant hormonal treatment of choice for postmenopausal estrogen receptor-positive breast cancer, are associated with an increased risk of musculoskeletal symptoms. The underlying cause of the symptoms is often attributed to estrogen depletion, yet all women treated with AIs have low estrogen levels and only a subset develop symptoms. Concentrations of circulating androgens may be mediating factors contributing to these side effects. The purpose of this study was to examine changes in androgen concentrations among women initiating AI therapy and to determine if concentrations are associated with musculoskeletal symptoms. Data were analyzed from a cohort study of 74 breast cancer patients for whom AI therapy was planned. Questionnaire data on symptoms were collected and blood was drawn prior to AI therapy (baseline) and then again at 3 and 6 months after baseline. Blood was assayed for testosterone, androstenedione, dehydroepiandrosterone-sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Free testosterone index (FTI) values were calculated using testosterone and SHBG measurements. The results showed that concentrations of all of the androgens increased over the study period, with statistically significant differences from baseline concentrations observed for the FTI at 3 and 6 months and for DHEAS at 6 months. Additionally, breast cancer patients with new onset or worsening of pain over the study period had a significantly smaller change in mean DHEAS concentration from baseline to 3 months (P = 0.04) and a marginally significant smaller change in mean DHEAS concentration from baseline to 6 months (P = 0.1) compared to those who reported no pain at all time points or no worsening of pain across the study period. Changes in testosterone, androstenedione, and the FTI were not associated with the onset or worsening of pain during the study period. Findings from this study suggest that higher DHEAS concentrations are associated with less AI-associated pain and should be further investigated.

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“…7-11 Unfortunately, since AIs nonselectively deplete estrogen in the whole body, they inevitably lead to severe musculoskeletal pain, reduction of bone density, and increased frequency of fractures and cardiovascular events. 12-16 …”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Norendoxifen Analogues with Dual Aromatase Inhibitory and Estrogen Receptor Modulatory Activities

Liu

Skaar

et al. 2015

J. Med. Chem.

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Both selective estrogen receptor modulators and aromatase inhibitors are widely used for the treatment of breast cancer. Compounds with both aromatase inhibitory and estrogen receptor modulatory activities could have special advantages for treatment of breast cancer. Our previous efforts led to the discovery of norendoxifen as the first compound with dual aromatase inhibitory and estrogen receptor binding activities. To optimize its efficacy and aromatase selectivity versus other cytochrome P450 enzymes, a series of structurally related norendoxifen analogues were designed and synthesized. The most potent compound, 4'-hydroxynorendoxifen (10), displayed elevated inhibitory potency against aromatase and enhanced affinity for estrogen receptors when compared to norendoxifen. The selectivity of 10 for aromatase versus other cytochrome P450 enzymes was also superior to norendoxifen. 4'-Hydroxynorendoxifen is therefore an interesting lead for further development to obtain new anticancer agents of potential value for the treatment of breast cancer.

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Musculoskeletal Adverse Events Associated with Adjuvant Aromatase Inhibitors

Cited by 38 publications

References 46 publications

The Association Between Breast Cancer Prognostic Indicators and Serum 25-OH Vitamin D Levels

The Association Between Breast Cancer Prognostic Indicators and Serum 25-OH Vitamin D Levels

Androgens and musculoskeletal symptoms among breast cancer patients on aromatase inhibitor therapy

Design and Synthesis of Norendoxifen Analogues with Dual Aromatase Inhibitory and Estrogen Receptor Modulatory Activities

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