Extended adjuvant endocrine therapy in hormone-receptor positive early breast cancer: Current and future evidence

Blok, Erik J.; Derks, M.G.M.; Hoeven, J.J.M. van der; Velde, Cornelis J.H. van de; Kroep, Judith R.

doi:10.1016/j.ctrv.2015.02.004

Cited by 34 publications

(14 citation statements)

References 65 publications

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“…One of the major uses of AIs is in risk reduction for recurrence and adjunctive treatment of estrogen receptorpositive breast cancer (8). Ductal breast cancer is currently the most common cancer of women in western Europe/North America, and the use of aromatase inhibitors challenges the current "gold standard" use of the SERM tamoxifen and the lesser used raloxifene (16,146). The theory is that, unlike SERMs, the inhibition or inactivation of aromatase suppresses serum estrogen levels and has no partial agonist activity (143).…”

Section: Aromatase Inhibitorsmentioning

confidence: 99%

Aromatase: Contributions to Physiology and Disease in Women and Men

2016

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Aromatase (estrogen synthetase; EC 1.14.14.1) catalyzes the demethylation of androgens' carbon 19, producing phenolic 18-carbon estrogens. Aromatase is most widely known for its roles in reproduction and reproductive system diseases, and as a target for inhibitor therapy in estrogen-sensitive diseases including cancer, endometriosis, and leiomyoma (141, 143). However, all tissues contain estrogen receptor-expressing cells, the majority of genes have a complete or partial estrogen response element that regulates their expression (61), and there are plentiful nonreceptor effects of estrogens (79); therefore, the effect of aromatase through the provision of estrogen is almost universal in terms of health and disease. This review will provide a brief but comprehensive overview of the enzyme, its role in steroidogenesis, the problems that arise with its functional mutations and mishaps, the roles in human physiology of aromatase and its product estrogens, its current clinical roles, and the effects of aromatase inhibitors. While much of the story is that of the consequences of the formation of its product estrogens, we also will address alternative enzymatic roles of aromatase as a demethylase or nonenzymatic actions of this versatile molecule. Although this short review is meant to be thorough, it is by no means exhaustive; rather, it is meant to reflect the cutting-edge, exciting properties and possibilities of this ancient enzyme and its products.

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Section: Aromatase Inhibitorsmentioning

confidence: 99%

Aromatase: Contributions to Physiology and Disease in Women and Men

2016

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“…Over the course of BrCa management, hormone therapy (such as tamoxifen and/or aromatase inhibitors) is used in combination with DNA damaging protocols [75]. DNA damaging chemotherapeutic drugs or radiation are used sequentially or simultaneously with hormone therapy in NR-positive disease [76].…”

Section: Hormone-dna Repair Crosstalk In Cancer: Clinical Relevancementioning

confidence: 99%

Linking DNA Damage and Hormone Signaling Pathways in Cancer

Schiewer

Knudsen

2016

Trends in Endocrinology & Metabolism

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DNA damage response and repair (DDR) is a tightly controlled process that serves as a barrier to tumorigenesis. Consequently, DDR is frequently altered in human malignancy, and can be exploited for therapeutic gain either through molecularly targeted therapies, or as a consequence of therapeutic agents that induce genotoxic stress. In select tumor types, steroid hormones and cognate receptors serve as major drivers of tumor development/progression, and as such are frequently targets of therapeutic intervention. Recent evidence suggests the existence of crosstalk mechanisms linking the DDR machinery and hormone signaling pathways that cooperate to influence both cancer progression and therapeutic response. These underlying mechanisms and their implications for cancer management will be discussed.

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“…Approximately two-thirds of all breast cancer patients were positive for ER, and could benefit from hormone therapy, but up to 50% of these cases had either de novo resistance or developed resistance during treatment (51,52). Hormone therapy or endocrine therapy, including antiestrogen, aromatase inhibitors, luteinizing hormone-releasing hormone (LH-RH) agonists, and selective estrogen receptor modulators (SERMs), interfere with the production and/or the action of estrogen and its receptors (53,54). Tamoxifen has been the standard endocrine treatment in both pre-and postmenopausal breast cancer patients, although aromatase inhibitors are the preferred option in postmenopausal patients, because aromatase enzymes catalyze estrogen production in adipose tissue, liver, muscle, and adrenal glands after menopause (55,56).…”

Section: Estrogen and Breast Cancermentioning

confidence: 99%

Hormonal regulation of immune modulators in human breast tissue

Morad¹

2015

Linköping University Medical Dissertations

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Breast cancer is the most common form of cancer and the second leading cause of malignancy-associated death in women worldwide. Estrogens are the main sex hormones in women. They are essential for the development and function of normal breast mammary glands; however, prolonged exposure to estrogens increases the risk of breast cancer development and progression. Approximately two-thirds of all breast cancer patients are positive for estrogen receptor (ER), but only 50% of those cases can benefit from antiestrogen therapy. In this thesis we investigated the effects of estrogen, diet modification, and anti-estrogen drugs on several immune modulators in normal human breast tissue. We used the microdialysis technique to sample the immune modulators in situ in normal human breast tissue, in malignant breast tissue, and in tumor tissue from both the immune competent mice with murine breast cancer and immune deficient mice bearing human breast tumors. Furthermore, we also used ex vivo culture of normal breast tissue and in vitro cell culture of breast cancer cell lines. A combined cell culture (co-culture) of breast cancer cell lines, together with the primary mature adipocytes, was also used in this thesis. In Paper I and Paper II, our results suggested that estrogen exerted both proinflammatory and pro-tumorigenic effects in normal human breast tissue. Estradiol increased extracellular interleukin-1β (IL-1β) and leptin levels and decreased IL-1Ra and adiponectin levels in normal human breast tissue. In contrast, tamoxifen decreased IL-1β and leptin levels and increased IL-1Ra and adiponectin levels, shifting the environment towards an antiinflammatory and antitumorigenic state. Diet modification with flaxseed for 30 days also increased IL-1Ra levels, creating an anti-inflammatory environment in normal breast tissue. In the breast cancer tissue, we found that extracellular IL-1β levels and leptin levels were significantly higher, whereas adiponectin levels were significantly lower, compared with normal adjacent breast tissue, which suggested a more proinflammatory state. In the third paper, our in vivo investigation of normal breast tissue revealed significant correlations between vascular endothelial growth factor (VEGF) and leptin, IL-1β and leptin, and between VEGF and IL-1β. No correlations were found in the abdominal subcutaneous (s.c.) fat tissue. Our in vitro inhibition experiments suggested that VEGF was a potent regulator of leptin, but that leptin was not a potent regulator of VEGF. Co-culture per se altered the release of VEGF and leptin and enhanced the effects of estradiol, compared with monocultures of the included cell types. In conclusion, the results presented in this thesis will increase the overall understanding of the role of estrogens in breast cancer, which may be useful in future treatment studies

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Extended adjuvant endocrine therapy in hormone-receptor positive early breast cancer: Current and future evidence

Cited by 34 publications

References 65 publications

Aromatase: Contributions to Physiology and Disease in Women and Men

Aromatase: Contributions to Physiology and Disease in Women and Men

Linking DNA Damage and Hormone Signaling Pathways in Cancer

Hormonal regulation of immune modulators in human breast tissue

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