Aromatase regulation and breast cancer

Reed, Michael J.; Purohit, Atul

doi:10.1046/j.1365-2265.2001.01276.x

Cited by 49 publications

(27 citation statements)

References 70 publications

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“…In our present study, aromatase mRNA was detected in both carcinoma and intratumoral stromal cells and the expression level was significantly higher in IDC than DCIS in these two cellular components (17-and 100-fold respectively). Previous in vitro studies demonstrated that breast carcinoma cells secrete various factors that induce aromatase expression in adipose fibroblasts (Zhou et al 2001), including prostaglandin E2 (Zhao et al 1996), interleukin (IL)-1, IL-6, IL-11, and tumor necrosis factora (Reed & Purohit 2001, Simpson & Davis 2001. On the other hand, it has been also reported that exogenous growth factors such as epidermal growth factor (Ryde et al 1992), transforming growth factor (Ryde et al 1992), and keratinocyte growth factor (Zhang et al 1998) stimulated aromatase activity in MCF-7 breast carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast

Shibuya¹,

Suzuki²,

Miki³

et al. 2008

Endocrine Related Cancer

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It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the intratumoral concentration of sex steroids has not been examined in DCIS. Therefore, in this study, we first examined the intratumoral concentrations of estradiol and 5a-dihydrotestosterone (DHT) using liquid chromatography/electrospray tandem mass spectrometry in DCIS. Intratumoral concentrations of both estradiol and DHT were threefold higher in DCIS than non-neoplastic breast tissues and estrogen-producing enzymes (aromatase, steroid sulfatase, and 17b-hydroxysteroid dehydrogenase type 1 (17bHSD1)), and androgen-producing enzymes (17bHSD5 and 5a-reductase type 1 (5aRed1)) were abundantly expressed in DCIS by real-time PCR and immunohistochemical analyses. The intratumoral concentration of DHT was significantly lower in IDC than DCIS, while the expression of aromatase mRNA in carcinoma cells and intratumoral stromal cells was significantly higher in IDC than those in DCIS. Immunohistochemistry for sex steroid-producing enzymes in DCIS demonstrated that 5aRed1 immunoreactivity was positively correlated with Ki-67 labeling index and histological grade and was also associated with an increased risk of recurrence in patients with DCIS examined. Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids. Therefore, estradiol and DHT may play important roles in the development of DCIS of the human breast.

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Section: Discussionmentioning

confidence: 99%

Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast

Shibuya¹,

Suzuki²,

Miki³

et al. 2008

Endocrine Related Cancer

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“…For example, phytochemicals, such as lignans, can be converted by microflora to enterolactone (7), which has been correlated with reduced breast cancer risk (8,9). Antibiotics could also theoretically decrease breast cancer risk by affecting the ability of microflora to modulate levels of circulating estrogens through deconjugation of bound estrogens in the gut, freeing them for reabsorption and circulation (10)(11)(12)(13). However, the disruption of the microflora by antibiotics is not uniform and may vary by dose and specific drug formulation (8).…”

Section: Antibiotics and Breast Cancer Riskmentioning

confidence: 99%

Use of Common Medications and Breast Cancer Risk

Moysich

Beehler

Zirpoli

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Prescription and over-the-counter medications are widely used in the United States and many western countries. More than two-thirds of women ages >45 years, who are at greatest risk for breast cancer, take prescription medication. In light of the ubiquitous nature of medication use and the fact that breast cancer remains the most common cancer in women, research on the role of medication use in breast cancer etiology is warranted. We summarize the epidemiologic evidence on the association between breast cancer risk and use of common medications, including antibiotics, antidepressants, statins, antihypertensives, and nonsteroidal anti-inflammatory drugs. Overall, there is little evidence that would implicate the use of antibiotics, antidepressants, statins, and antihypertensives in the etiology of breast cancer. Although several prospective studies and a randomized low-dose aspirin chemoprevention trial have not shown lower risk of breast cancer among aspirin users, most studies that have examined the potential chemoprotective effect of nonsteroidal anti-inflammatory drugs have shown significant risk reductions for regular and prolonged use of these drugs. The existing literature on the role of medication use in breast carcinogenesis is complicated. Interpretation of the evidence is hampered due to major methodologic differences across studies, including exposure assessment, exposure classification, and adjustment for potential confounding variables. These differences largely stem from the fact that the majority of articles on this topic represent secondary data analyses from studies with inadequate information on exposure or confounders. Thus, future epidemiologic studies specifically designed to study these ubiquitous and biologically plausible exposures are warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1564 -95)

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“…Reed et al [52] proposed that the sulfatase pathway might be more important than the aromatase route for intratumoral estrogen synthesis in breast carcinomas, because aromatase mRNA expression was reported to have no significant prognostic value. STS inhibitors are currently being developed by several groups, and the results of a phase I study suggested that STS inhibitor may be effective in hormone-dependent breast carcinoma including those that progressed on aromatase inhibitors [53].…”

Section: Estrogen Deprivation Therapies In Breast Carcinoma Patientsmentioning

confidence: 99%

Aromatase in Human Breast Carcinoma as a Key Regulator of Intratumoral Sex Steroid Concentrations

et al. 2008

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Abstract. It is well-known that estrogens are closely involved in the growth of human breast carcinomas, and that the great majority of breast carcinoma express estrogen receptors. Recent studies have demonstrated that estrogens are locally produced and act on the breast carcinoma tissue. Among these pathways, aromatase is a key enzyme for intratumoral production of estrogens in breast carcinomas, and aromatase inhibitors are currently used in the breast carcinoma in postmenopausal women as an estrogen deprivation therapy. This review summarizes the results of recent studies on the expression and regulation of aromatase in breast carcinoma tissues, and discusses the potential biological and/or clinical significance of aromatase. Aromatase is abundantly expressed in various cell types, such as carcinoma cells, intratumoral stromal cells, and adipocytes adjacent to the carcinoma, in breast carcinoma tissues. Further, a key regulator for aromatase expression differed according to cell type. In addition, aromatase suppressed in situ production of bioactive androgen, 5α-dihydrotestosterone (DHT), in breast carcinoma. Aromatase inhibitors may thus have additional antiproliferative effects through increasing local DHT concentration with estrogen deprivation.

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Aromatase regulation and breast cancer

Cited by 49 publications

References 70 publications

Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast

Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast

Use of Common Medications and Breast Cancer Risk

Aromatase in Human Breast Carcinoma as a Key Regulator of Intratumoral Sex Steroid Concentrations

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