Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis

Šestak, Ivana; Cuzick, Jack; Sapunar, Francisco; Eastell, Richard; Forbes, John F.; Bianco, Angelo Raffaele; Buzdar, Aman U.

doi:10.1016/s1470-2045(08)70182-7

Cited by 194 publications

(145 citation statements)

References 27 publications

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“…(14,15) Appropriate and specific inhibition of HSD-1 in cancerous tissue deserves further study, because it might be effective in decreasing the intratumoral E2 concentration without decreasing the systemic E1 concentration, which is the main effect of AI, and causes side-effects, such as bone loss and joint symtoms. (35,37) Of the six steroids examined, DHEA was the most abundant, as has been reported in many other studies. (19) The Adione concentration was lower than the DHEA concentration by an order of magnitude, although the premenopausal ⁄ postmenopausal serum ⁄ tumor tissue pattern was quite similar.…”

Section: Discussionsupporting

confidence: 69%

Sex steroid hormones in pairs of tumor and serum from breast cancer patients and pathobiological role of androstene‐3β, 17β‐diol

et al. 2011

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Estrogens play an important role in the pathobiology of breast cancer. In postmenopausal women, peripheral synthesis of estrogens from adrenal/ovarian androgens, dehydroepiandrosterone (DHEA) or androstenedione (Adione), by estrogen-metabolizing enzymes is important. Besides estrone (E1) and estradiol (E2), androgen metabolites, such as androstene-3b, 17b-diol (Aenediol) or 5a-androstane-3b, 17b-diol (Aanediol), are known to have estrogenic functions, although they have been studied much less in breast cancer. To precisely elucidate steroid metabolism in breast cancer patients and to identify the pathobiological role of estrogenic androgen metabolites, concentrations of DHEA, Adione, Aenediol, Aanediol, E1, and E2 in pairs of serum and tumor tissue from patients with primary breast cancer were measured by liquid chromatography-tandem mass spectrometry. Cell proliferation assays using Aenediol were performed for four breast cancer cell lines. Serous E2 concentration was extremely low in postmenopausal women; however, a marked increase in tumor tissue was observed in hormone receptor-positive cases. E1 concentration, in contrast, was sustained at a higher level, even in postmenopausal serum, and did not increase in tumor tissue irrespective of the hormone receptor status. Dehydroepiandrosterone was most abundant in all samples, and exhibited a similar pattern as Adione and Aenediol. 5a-Androstane-3b, 17b-diol was undetectable in most samples. Androstene-3b, 17b-diol proliferated estrogen receptor-apositive breast cancer cells in the absence of E2. The intratumoral increase of E2, but not E1, in hormone receptor-positive postmenopausal breast cancer tissue, as well as the proliferative role of Aenediol, was elucidated. (Cancer Sci 2011; 102: 1848-1854 E strogen plays an important role in the pathobiology of breast cancer.(1,2) In postmenopausal women, in whom ovarian function has decreased, the peripheral metabolism of estrogens via estrogen-metabolizing enzymes is important (Fig. 1). (3,4) Peripheral aromatase converts circulating androgens, such as dehydroepiandrosterone (DHEA) and androstenedione (Adione), from the adrenal gland or ovary into estrogens. Steroid sulfatase (STS) hydrolyzes biologically-inactive sulfates of sex steroids, both estrogens and androgens, producing active steroids. 17b-Hydroxysteroid deydrogenase (HSD)-1 converts estrone (E1) into estradiol (E2), the most potent estrogen. In breast cancer tissue, aromatase, (3-7) STS, (8)(9)(10) and HSD-1 (11) have been reported to be abundant. An increase of E2 concentration in cancerous tissue, compared with the serum in postmenopausal women, has been explained by those enzymes localized in the tumor tissue.(4) Estrone sulfotransferase and HSD-2 play opposite roles to STS and HSD-1, respectively (Fig. 1). Aromatase inhibitors (AI) have been standardized for the treatment of postmenopausal patients with hormone receptor-positive breast cancers, (12) in the expectation of decreasing estrogens. Inhibitors of STS (13) or HSD-1 (14,15) have been also devel...

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Section: Discussionsupporting

confidence: 69%

Sex steroid hormones in pairs of tumor and serum from breast cancer patients and pathobiological role of androstene‐3β, 17β‐diol

et al. 2011

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“…As a consequence of estrogen deprivation, the occurrence of joint pain increases with age and reaches a peak in women aged 50-59 years [8,21,22].…”

Section: Discussionmentioning

confidence: 99%

“…Actually comparisons of results of different studies must take into account the baseline characteristics of the patients: we included only patients who reported pain as a criterion of entry in our trial, in contrast with Sestak et al [22] who studied patients without any pre-existing joint symptoms. Musculoskeletal pain is an adverse event often reported with this class of agent, AIs can trigger symptoms which can be completely resolved after treatment discontinuation [23].…”

Section: Discussionmentioning

confidence: 99%

Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study

Briot

Tubiana-Hulin

Bastit

et al. 2009

Breast Cancer Res Treat

104

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To cite this version:Karine Abstract The objective of the present study was to evaluate the effect of the switch of aromatase inhibitors (AIs) on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer. This was a 6-month, prospective, non-randomized, multicenter study. Patients who had discontinued anastrozole due to musculoskeletal symptoms were eligible to participate in this study, and received letrozole, which was initiated 1 month after anastrozole discontinuation. Musculoskeletal symptoms were systematically assessed for severity, location of the symptoms, presence of swelling and of morning stiffness by the oncologist patients when patients stopped taking their anastrozole, 1 month after the discontinuation of anastrozole, and 1, 3, and 6 months after initiating the letrozole therapy. The primary endpoint was the percentage of patients who discontinued letrozole due to the severe musculoskeletal symptoms. After switching from anastrozole therapy, and at the end of the 6-month letrozole treatment, 128 (71.5%) out of 179 patients (61.3 ± 8.4 years) continued with letrozole. Fifty-one patients (28.5%) discontinued treatment due to severe joint pain. At the end of the 6-month, 116 patients (73.9%) had arthralgia, 33 (21.0%) myalgia, 25 (15.9%) arthritis, 22 (14.0%) tendinitis, and 20 (12.7%) polyalgic syndrome. Bivariate analysis of the factors associated with letrozole discontinuation showed that the duration of a prior anastrozole treatment was a significant predictor (P = 0.04). This study shows that in patients intolerant to one AI, switching to another agent allows a higher proportion of patients to continue the therapy and maximize hormonal adjuvant therapy and disease outcome benefits.

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“…The peak occurrence for joint symptoms was 6 months. There was a higher rate of arthralgia in anastrozole patients who had received prior chemotherapy (41.8% vs. 33.6%) [42]. The median time to symptoms was also shorter in this group (9.1 months vs. 15.9 months).…”

Section: Upfront Usementioning

confidence: 73%

“…In addition, there are limited data regarding the time course and resolution of symptoms. The ATAC trial did show that the highest incidence of joint symptoms occurred in the first year [42].…”

Section: Adverse Event Reportingmentioning

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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Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis

Cited by 194 publications

References 27 publications

Sex steroid hormones in pairs of tumor and serum from breast cancer patients and pathobiological role of androstene‐3β, 17β‐diol

Sex steroid hormones in pairs of tumor and serum from breast cancer patients and pathobiological role of androstene‐3β, 17β‐diol

Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study

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

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