IGF status is altered by tamoxifen in patients with breast cancer

Campbell, Maeli J.; Woodside, Jayne V.; Secker-Walker, Jonathan; Titcomb, Ann; Leathem, Anthony

doi:10.1136/mp.54.5.307

Cited by 27 publications

(19 citation statements)

References 19 publications

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“…Four other studies have examined the effect of soy on IGF status (unpublished observations, Wangen et al, 2000;Aukema and Housini, 2001;Woodside & Campbell, 2001;Khalil et al, 2002). In a rat model of polycystic kidney disease, soy protein feeding resulted in reduced IGF-1 in both normal and affected male animals (Aukema & Housini, 2001).…”

Section: Discussionmentioning

confidence: 99%

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Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study

et al. 2003

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Background: Isoflavones are estrogen-like plant compounds that may protect against cardiovascular disease and endocrineresponsive cancer. Isoflavones may, because of their ability to act as selective estrogen receptor modulators, alter insulin-like growth factor (IGF) status. Objective: The aim of this study was to assess the effect of 1-month isoflavone supplementation (86 mg/day red clover-derived isoflavones) on IGF status. Design and subjects: Healthy pre-(n ¼ 16) and postmenopausal (n ¼ 7) women were invited to take part in a randomised, placebo-controlled crossover study with a minimum 2-month washout period. Results: For premenopausal subjects, the change in IGF-1, IGF-BP1 and IGF-BP3 assessed at different points of the menstrual cycle did not differ between isoflavone and placebo phase. However, the change in IGF-1, when examined pre-and postsupplementation, was nonsignificantly reduced (P ¼ 0.06) on the isoflavone supplement compared to placebo. For postmenopausal subjects, the change in IGF-1, IGF-BP1 and IGFBP-3 concentrations over the supplementation period did not differ between isoflavone or placebo phase. Isoflavones increased HDL in postmenopausal women compared to placebo (P ¼ 0.02) but did not alter either cholesterol or triacylglycerol concentrations, and had no effect on antioxidant status. Conclusions: This study shows that 1-month supplementation with red clover isoflavones has a positive effect on HDL cholesterol, but at most a small effect on IGF status in premenopausal and no effect in postmenopausal subjects. Further studies are required to ascertain the role these dietary compounds may have to play in breast cancer prevention. Sponsorhip: The isoflavone and placebo supplements were kindly supplied by Novogen (North Ryde, Sydney, Australia). This study was supported by Action Against Breast Cancer registered charity number 1020967.

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Section: Discussionmentioning

confidence: 99%

“…Tamoxifen has been shown to lower IGF-1 concentrations in breast cancer patients by up to 30% (Pollak et al, 1990;Campbell et al, 2001). Isoflavones are a class of phytoestrogens that may have a variety of potential health benefits in endocrine-responsive cancers and cardiovascular disease (Bingham et al, 1998;This et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study

et al. 2003

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“…pegvisomant), IGF-IR antibodies and analogs of IGF-I (Khandwala et al 2000). Clinical studies have demonstrated the efficacy of the antiestrogen tamoxifen, which decreases the IGF-I/IGFBP-3 ratio via increased IGFBP-3 (Campbell et al 2001) and reduced IGF-I levels (Osborne 1998), in the treatment and prevention of breast cancer (Fisher et al 1998). Another estrogen receptor modulator, raloxifene (used for the treatment and prevention of osteoporosis in postmenopausal women) was shown to decrease the IGF-1/IGFBP-3 ratio and has been proposed for future studies in breast cancer prevention (Torrisi et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Deregulation of the IGF axis in cancer: epidemiological evidence and potential therapeutic interventions.

Jerome¹,

Shiry²,

Leyland‐Jones³

2003

Endocrine-Related Cancer

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The IGF system performs a fundamental role in the regulation of cellular proliferation, differentiation and apoptosis. These diverse biological actions are mediated primarily by IGF association with the type I IGF receptor (IGF-IR), which is in turn regulated by a group of high-affinity IGF-binding proteins (IGFBP-1 to -6). All of the IGFBPs can have growth-inhibitory effects by competitively binding IGFs and preventing their association with the IGF-IR. IGFBP-3 is the most abundant binding protein in the circulation and controls the actions of the IGFs by regulating their distribution and bioavailability to target tissues. Disruptions in the balance of IGF system components leading to excessive proliferation and survival signals have been implicated in the development of different tumor types. Epidemiological evidence indicates that increased levels of IGF-I, reduced levels of IGFBP-3 or an increased ratio of IGF-I to IGFBP-3 in the circulation are associated with an increased risk for the development of several common cancers, including those of the breast, prostate, lung and colon. The results of preclinical studies indicate that a diversity of interventions which antagonize IGF-IR signaling or augment IGFBP-3 function inhibit tumor cell growth in models of human cancers. A more comprehensive understanding of the interplay between cellular targets of the IGF system and antineoplastic agents will facilitate the development of novel strategies for the prevention and treatment of cancer.

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“…Treatment of breast cancer patients with the antiestrogens tamoxifen or raloxifene decreased the IGF-I/IGFBP-3 molar ratio such that lower amounts of circulating IGF-I were available for mitogenic signaling [122,123]. Somatostatin analogues also reduce IGF signaling by reducing IGF-I levels.…”

Section: Insulin-like Growth Factor-i-receptor-targeted Therapymentioning

confidence: 99%

Growth Factor Receptors in Breast Cancer: Potential for Therapeutic Intervention

2003

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IGF status is altered by tamoxifen in patients with breast cancer

Abstract: Tamoxifen increases IGF-BP3 and IGF-BP1 concentrations. It also decreases the IGF-1 to IGF-BP3 ratio but this effect may be limited after long term use. Longer follow up, with larger numbers of patients, should determine when, and for how long, tamoxifen can reduce circulating IGF-1.

Cited by 27 publications

References 19 publications

Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study

Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study

Deregulation of the IGF axis in cancer: epidemiological evidence and potential therapeutic interventions.

Growth Factor Receptors in Breast Cancer: Potential for Therapeutic Intervention

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