High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: A renewed role for adrenalectomy

Morris, Katherine T.; Toth-Fejel, Su Ellen; Schmidt, Joshua H.; Fletcher, William S.; Pommier, Rodney F.

doi:10.1067/msy.2001.118378

Cited by 49 publications

(33 citation statements)

References 9 publications

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“…Further studies have also proved that DHEA and Adiol can directly activate the ER and stimulate the proliferation of breast cancer cells [116]. Moreover, recent research has shown that DHEAS, DHEA, and Adiol can stimulate the proliferation of breast cancer cells in vitro and induce mammary tumors in vivo [117] their ability to do so is blocked by the ER antagonist nafoxidene, but not by aromatase inhibitors. These results provide strong evidence that the stimulation of cell growth by DHEAS occurs via an aromatase-independent pathway that can be potentially blocked by an STS inhibitor.…”

Section: Gene Expression and Regulationmentioning

confidence: 98%

Oestrogen producing enzymes and mammary carcinogenesis: a review

Subramanian

Salhab

Mokbel

2007

Breast Cancer Res Treat

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There is a large and compelling body of epidemiological and experimental evidence that oestrogens are instrumental in the aetiology of breast cancer. Their mechanisms of action are varied, including stimulation of cellular proliferation through receptor-mediated hormonal activity, increasing genetic mutation rates through cytochrome P450-mediated metabolic activation, and induction of aneuploidy. The local biosynthesis of oestrogens especially in postmenopausal women is believed to play a very important role in the pathogenesis and development of hormone dependent breast carcinoma and the over-expression of regulatory enzymes seems to be associated with the development of a more aggressive disease and associated with poor outcome and increased local and distant recurrences. In this article we highlight the role of CYP19 gene expression and aromatase activity in mammary carcinogenesis. Other oestrogen producing (17-beta-hydroxysteroid dehydrogenase and steroid sulphatase) and catalyzing enzymes (3-beta-hydroxysteroid dehydrogenase, Oestrogen sulfotransferase, CYP1A1, CYP1B1, and CYP3A4) are also discussed in some detail. Understanding the mechanisms that regulate these enzymes is crucial to the development of new endocrine therapies in post-menopausal females with hormone dependant breast cancer. Currently, third generation aromatase inhibitors has revolutionized the treatment of oestrogen dependant breast cancer. However, the important role of both STS and 17-beta-HSD type 1 in local oestrogen production provides novel potential targets for endocrine therapy. Such endocrine therapy is currently being explored and the development of STS inhibitors, combined aromatase/steroid sulfatase inhibitors and 17-beta-HSD type 1 inhibitors is underway with promising initial results.

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Section: Gene Expression and Regulationmentioning

confidence: 98%

Oestrogen producing enzymes and mammary carcinogenesis: a review

Subramanian

Salhab

Mokbel

2007

Breast Cancer Res Treat

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“…18,24,25 We previously demonstrated that serum levels of DHEA-S of 90 µg/dL or more (Ն2.43 µmol/L) are a risk factor for disease progression in women with stage IV disease treated with third-generation aromatase inhibitors. 26 We subsequently reported that similar DHEA-S levels are a risk factor for disease progression in women treated with adjuvant tamoxifen citrate therapy. 27 Concomitant in vitro work demonstrated that DHEA-S used the ER to induce cell proliferation, an effect that was blocked by tamoxifen in a dose-depen- dent manner.…”

Section: Herapeutic Approachesmentioning

confidence: 98%

Estrogen and Androgen Receptors as Comediators of Breast Cancer Cell Proliferation

Toth-Fejel¹

2004

Arch Surg

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“…What happens to androgens during aromatase inhibition remains to be clarified. Morris and co-workers observed that high levels of an adrenal androgen, dehydroepiandrosterone-sulfate (DHEA-S), predict breast cancer progression during the new aromatase inhibitor therapy with an environment of low estrogen [7]. Estrogenic effects from DHEA-S were observed in tissue culture studies.…”

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confidence: 94%