Antiestrogenic tamoxifen and toremifene increase serum leptin levels in postmenopausal breast cancer patients

Marttunen, Merja B.; Andersson, Sture; Hietanen, Päivi; Karonen, Sirkka-Liisa; Koistinen, Hannu; Koivisto, Veikko A.; Tiitinen, Aila; Ylikorkala, Olavi

doi:10.1016/s0378-5122(00)00121-3

Cited by 32 publications

(23 citation statements)

References 24 publications

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“…The negative correlation between baseline serum adiponectin levels and BMI at baseline did not persist throughout the study. These findings were consistent with previous findings reported in the literature [45,46]. Changes in body composition and serum adiponectin levels were similar in both TMX and AI groups.…”

Section: Discussionsupporting

confidence: 93%

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The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study

Akyol¹,

Demir²,

Alacacıoğlu³

et al. 2015

Chemotherapy

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Background: A limited number of studies have been conducted on the effects of hormonal therapy with tamoxifen (TMX) or aromatase inhibitors (AIs) on plasma levels of leptin and adiponectin, as well as body composition in breast cancer (BC) patients. Therefore, we aimed to analyze the relationship between adipocytokines and body composition as well as the effects of TMX and AIs on plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and body composition. Methods: Patients were treated with either TMX or AI according to their menopausal status after adjuvant radiotherapy. Changes in body composition and serum leptin and adiponectin levels were evaluated. We recorded the type of hormonal therapy, BMI, waist/hip ratio (WHR), leptin and adiponectin levels at study entry, and after 6 and 12 months. Results: From baseline to the 6- and 12-month follow-ups, there were statistically significant increases in WHR (p = 0.003), fat mass (p = 0.041), and serum leptin (p < 0.001) and adiponectin levels (p < 0.001). The changes in body composition and serum leptin and adiponectin levels were similar in TMX and AI groups. A statistically significant decrease was found in total body water and LAR (p < 0.001). Although weight and body fat percentage increased, such increases were not statistically significant. A positive correlation was found between baseline BMI and serum leptin levels. This correlation was maintained at 6 and 12 months. The negative correlation found between serum adiponectin levels at baseline and baseline BMI did not last throughout the study. Conclusion: In this study, increased leptin and adiponectin levels and a decreased LAR were found in both AI and TMX groups. These changes might have occurred through both mechanisms of hormonal therapy and body composition changes. Therefore, AIs and TMX may exert their protective effects for BC patients by decreasing LAR rather than affecting leptin or adiponectin alone.

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Section: Discussionsupporting

confidence: 93%

“…[46] randomized 30 postmenopausal women into two treatment groups: TMX 20 mg/day and toremifene 40 mg/day. The patients were found to display increased weight and leptin levels at the 6- and 12-month follow-ups, but no relationship was detected between leptin levels and weight changes.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study

Akyol¹,

Demir²,

Alacacıoğlu³

et al. 2015

Chemotherapy

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“…It is interesting to note how two recent studies have reported increased serum leptin levels in women receiving tamoxifen as a treatment for breast cancer (42,43). On the other hand, leptin was recently reported to increase aromatase activity in woman luteinized granulosa cells (18) FIG.…”

Section: Discussionmentioning

confidence: 99%

Leptin Enhances, via AP-1, Expression of Aromatase in the MCF-7 Cell Line

Catalano

Marsico

Giordano

et al. 2003

Journal of Biological Chemistry

264

203

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Leptin, a product of adipocytes, is involved in the regulation of body weight and results strongly correlated to body fat content. An excess of fat mass represents a breast cancer risk factor particularly in postmenopausal women, where estrogen production by adipose tissue through its own aromatase activity stimulates tumor progression. Leptin stimulates estrogen production through the increase of aromatase expression and activity in human luteinized granulosa cells and adipose stromal cells. In the present study, we have examined the possible link that exists between leptin and breast cancer, focusing our attention on the direct effect of leptin on aromatase activity, which may enhance estrogen production and induce tumor cell growth stimulation. We have shown that leptin enhances aromatase mRNA expression, aromatase content, and its enzymatic activity in MCF-7. Aromatase expression appears to be regulated by tissue-specific promoter. It has been demonstrated that promoters II and 1.3 are the major promoters that drive aromatase expression in MCF-7. Transient transfection experiments using vector containing human aromatase promoters II and 1.3 sequence fused with luciferase reporter gene demonstrated that leptin is able to activate this promoter. In the presence of either mitogen-activated protein kinase inhibitor PD 98059 or ERK2 dominant negative as well as in the presence of STAT3 dominant negative, the stimulatory effects of leptin on aromatase promoter, enzymatic activity, and aromatase protein content were inhibited. Functional studies of mutagenesis and electrophoretic mobility shift assay revealed that the AP-1 motif is important in determining the up-regulatory effects induced by leptin on aromatase expression in MCF-7.

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“…An elevation in the serum leptin levels of tamoxifen-treated postmenopausal breast cancer patients had been reported previously and was considered to represent the well-recognized estrogen-like systemic effects of the antiestrogen (Marttunen et al 2000). However, in general, the patients included in Table 3 were investigated before the initiation of postsurgical treatment and a confounding effect of tamoxifen adjuvant therapy does not account for the observed discrepancies between the results of the individual studies.…”

Section: Adipokines As Circulating Hormones In Breast Cancer Leptinmentioning

confidence: 96%

Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression

Vona-Davis

Rose²

2007

Endocr Relat Cancer

443

359

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Adipokines (leptin, adiponectin, and hepatocyte growth factor (HGF)) secreted from adipose tissue have come to be recognized for their contribution to the mechanisms by which obesity and related metabolic disorders influence breast cancer risk. In this review, we discuss the direct and indirect effects of these protein factors on the biological and clinical aspects of breast cancer biology, and emphasize their distinctive modes of action through endocrine-, paracrine-, and autocrine-mediated pathways. The stimulatory effects of leptin on breast cancer growth were considered to occur primarily via activation of the estrogen receptor; however, new evidence suggests that leptin may be acting on downstream cell signaling pathways in both estrogendependent and -independent cell types. Another secretory adipokine, HGF, may act largely not only to promote tumor cell invasion, but also to enhance tumor growth indirectly by stimulating angiogenesis. In contrast, adiponectin, an endogenous insulin sensitizer, exerts a direct growthinhibitory effect on tumor cells by downregulating cell proliferation and upregulating apoptosis, and also inhibits tumor-related angiogenesis.

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Antiestrogenic tamoxifen and toremifene increase serum leptin levels in postmenopausal breast cancer patients

Cited by 32 publications

References 24 publications

The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study

The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study

Leptin Enhances, via AP-1, Expression of Aromatase in the MCF-7 Cell Line

Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression

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