Aromatase activity in breast tissue

doi:10.1016/0960-0760(91)90026-2

The Journal of Steroid Biochemistry and Molecular Biology

Volume 39, Issue 5, Part 2, November 1991, Pages 783-790

https://doi.org/10.1016/0960-0760(91)90026-2 Get rights and content

Abstract

Aromatase activity may be detected both in breast adipose tissue and breast cancer in levels similar to or greater than those in other peripheral tissues. Factors influencing such local biosynthesis have been sought. Of 247 primary breast cancers investigated, 178 showed evidence of oestrogen biosynthesis. No significant relationships were found between either the presence or levels of activity and tumour histopathology, patient characteristics (such as age and menopausal status), disease stage and prognosis (determined by disease-free interval and survival after primary treatment). Aromatase was more likely to be found in cellular cancers and those which were oestrogen receptor-positive, but these were not absolute associations, activity being detected in tumours with all degrees of cellularity and both receptor-positive and receptor-negative cancers. However, in a small group of patients with metastatic oestrogen receptor-positive tumours, response to the aromatase inhibitor, aminoglutethimide, seemed confined to tumours with aromatase activity. Oestrogen biosynthesis was detected in all specimens of breast adipose tissue examined. Activities were higher in fat from breast cancer patients compared with that from women with benign breast disease. In breasts with cancer, levels were higher in quadrants bearing tumour compared with those without evidence of malignancy. It is suggested that either enhanced aromatase in breast fat promotes the appearance of overt cancer or tumour factors induce aromatase in surrounding fat. Finally, although no significant correlations were detected in postmenopausal women between local aromatase activity and endogenous oestrogens in breast cancer, perfusion studies show that in situ oestrogen biosynthesis is primarily responsible for oestrogen levels in the majority of breast tissues. These data suggest that local aromatase activity may influence events within the breast and may be associated with the natural history and progression of certain malignancies.

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There are more references available in the full text version of this article.

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The article reviews fundamental principles of bone biology and integrates bone-specific growth factors, cytokines and hormones that regulate bone modeling and remodeling as well as the dynamics and complexity of bone as an organ system. Basic bone biology is underscored to provide a roadmap for designing and developing bone regeneration therapeutics in dentistry, craniomaxillofacial and orthopedic arenas.
Structural and functional characterization of aromatase, estrogen receptor, and their genes in endocrine-responsive and -resistant breast cancer cells
2016, Journal of Steroid Biochemistry and Molecular Biology
Citation Excerpt :
Breast adipose tissues from breast cancer patients show an increase in aromatase expression through promoters II and I.3 [66], also high aromatase activity in the quadrant containing the tumor has been detected [66,72,73]. Therefore, elevated levels of aromatase expression lead to local synthesis of estrogen production in the breast tumor [65,74–79]. Aromatase deficiency is an extremely rare disorder in humans.
Aromatase and estrogen receptor α (ER) are two key proteins for the proliferation of endocrine-responsive and –resistant breast cancers. Aromatase is an enzyme involved in the conversion of androgen (such as testosterone) to estrogen (such as 17β-estradiol). It is also a very effective therapeutic target for the treatment of endocrine-responsive breast cancer. Comparing endocrine-responsive and -resistant breast cancer, aromatase protein levels do not change significantly. Aromatase activity; however, can be increased via PI3K/Akt/IGFR signaling pathways in endocrine resistant cells. The activity of aromatase has been reported to be modulated by phosphorylation. The ER is an important steroid nuclear receptor in the proliferation of both endocrine-responsive and -resistant cells. Although the mutation or amplification of ER can cause endocrine resistance, it is not commonly found. Some point mutations and translocation events have been characterized and shown to promote estrogen-independent growth. Phosphorylation by cross-talk with growth factor pathways is one of the main mechanisms for ligand-independent activation of ER. Taken together, both ER and aromatase are important in ER-dependent breast cancer and the development of endocrine resistance.
Estradiol measurement in translational studies of breast cancer
2015, Steroids
Citation Excerpt :
Much interest has focused on issue estrogen levels since van Landeghem [42] and others three decades ago reported breast cancer tissue E2 levels a magnitude higher as compared to plasma levels in postmenopausal women. Thus, issues have been raised with respect to local estrogen synthesis by aromatization [43] as well as de-conjugation of E1S [44]. Using our sensitive radioimmunoassay’s on tissue samples following HPLC purification (Fig. 2), we were able to detect tissue levels of E2 as well as E1 and E1S with high degree of sensitivity [45].
Plasma estrogen measurement with use of radioimmunoassays has been instrumental in the development of aromatase inhibitors for endocrine therapy of postmenopausal breast cancer. However, due to low plasma estrogen concentrations in postmenopausal women, direct radioimmunoassays lack the sensitivity required. While certain laboratories have developed highly sensitive assays for research purposes revealing plasma estrogen suppression consistent with results from tracer studies, such assays are time and labor-consuming due to need for pre-analytical chromatographic purification, sample concentration and sometimes conversion of precursors to products. While novel chromatographic methods involving mass spectrometry analysis are likely to replace such radioimmunoassays in the future, so far a limited number of laboratories have developed suitable assays with a detection limit (around 1 pM) that is required for analyzing plasma estrogen levels in patients during treatment with potent aromatase inhibitors.
The intracrinology of breast cancer
2015, Journal of Steroid Biochemistry and Molecular Biology
The importance of intracrinology, or in situ production of steroids from circulating precursors, in breast cancer has been firmly established in estrogen actions on postmenopausal patients. Expression levels of various steroid synthesizing and/or metabolizing enzymes have been examined in human breast cancer tissues by a number of groups. The enzymes examined include those capable of converting circulating DHEA-S to sex steroids (STS and 3βHSDΔ4-5 isomerase), the group of enzymes that modulate the strength of both androgens and estrogens (17βHSD family) as well as the androgenic 5αR enzymes and the estrogenic aromatase enzyme. In addition to these DHEA-related metabolism pathways, other intracrine pathways involving progesterone and cholesterol have also been examined. Some risk factors of breast cancer development, including obesity, have also been postulated to interact with steroid metabolising pathways. In this review, we aimed to summarise the current state of knowledge regarding intracrine metabolism including expression levels of various enzymes and receptors, focusing particularly upon the importance of the production of biologically potent steroids from circulating sulfated precursors such as DHEA-S. In addition, we attempted to summarise the factors, both steroidal and non-steroidal, involved in the regulation of these enzymes and propose future directions for research in this particular field. The concept of intracrinology was first proposed over 20 years ago but there still remain many unanswered questions which could open new horizons for the understanding of intracrine metabolism in the breast.
This article is part of a Special Issue entitled ‘Essential role of DHEA’.
Intracardiac extension of intravenous leiomyomatosis in a woman with previous hysterectomy and bilateral salpingo-oophorectomy: A case report and review of the literature
2014, Human Pathology: Case Reports
Citation Excerpt :
Though we do not have serum estrogen levels measured in our patient, taking into consideration the body habitus and age of our patient, it is possible that there was a higher than expected level of estrogen, causing progression of IVL. Similarly, there is evidence suggesting that estrogen produced by adipose tissue has a critical role in breast cancer genesis [19]. The possibility of such extra sources of endogenous estrogen production may explain the rapid course of IVL growth seen in our patient which is remarkable given the characteristic minimal to absent mitotic activity of leiomyomas.
Intravenous leiomyomatosis (IVL) is a rare tumor, characterized by benign smooth muscle growth inside veins. The tumor arises from the uterine venous wall or uterine leiomyomas and is usually confined to the pelvic cavity. However, on rare instances, it may extend into the cardiac cavity (Pathol Annu 1988;23 Pt 2:153–158), and the pulmonary system (Arch Gynecol Obstet 2001;264:209–210). Treatment consists of surgical removal of the tumor, cessation of ovarian function and avoidance of estrogen replacement therapy (Gynecol Obstet Invest 2004;58:168–170). We present a case of intravenous leiomyomatosis with extension from IVC to RA, RV and PA, with an unusually rapid course of progression in the absence of estrogen (TAH-BSO, without concomitant hormonal therapy).
Intracrine oestrogen production and action in breast cancer: An epigenetic focus
2013, Journal of Steroid Biochemistry and Molecular Biology
Epigenome changes have been widely demonstrated to contribute to the initiation and progression of a vast array of cancers including breast cancer. The reversible process of many epigenetic modifications is thus an attractive feature for the development of novel therapeutic measures. In oestrogen receptor α (hereinafter referred to as ER) positive tumours, endocrine therapies have proven beneficial in patient care, particularly in postmenopausal women where two-thirds of tumours are oestrogen dependent. However, resistance to such therapies is a common feature amongst individuals. In the current review, we discuss the influence that epigenetics has on oestrogen dependent breast cancers, in particular (i) the production of intracrine oestrogen in postmenopausal women, (ii) the action of oestrogen on epigenetic processes, and (iii) the links between epigenetics and endocrine resistance and the current advancements in epigenetic therapy that target this process.
This article is part of a Special Issue entitled ‘CSR 2013’.

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The Journal of Steroid Biochemistry and Molecular Biology

Abstract

References (18)

The interconversion and aromatization of androgens by human adipose tissue

J. Steroid Biochem.

Steroid metabolism by human breast and rat mammary carcinoma

Steroids

The importance of local synthesis of estrogen within the breast

Steroids

The conversion of androstenedione to estrone, estradiol and testosterone in breast tissue

J. Steroid Biochem.

Relationship between tumour aromatase activity, tumour characteristics and response to therapy

J. Steroid Biochem. Molec. Biol.

Aromatization of androstenedione by cultured human fibroblasts

J. Clin. Endocr. Metab.

Aromatization of androgens by muscle and adipose tissue in vitro

J. Clin. Endocr. Metab.

Significance of aromatase activity in human breast cancer

Cancer Res.

Oestradiol synthesis from C19 steroids by human breast cancer

Br. J. Cancer

Cited by (123)

6.2 Bone tissue engineering: Growth factors and cytokines

Structural and functional characterization of aromatase, estrogen receptor, and their genes in endocrine-responsive and -resistant breast cancer cells

Estradiol measurement in translational studies of breast cancer

The intracrinology of breast cancer

Intracardiac extension of intravenous leiomyomatosis in a woman with previous hysterectomy and bilateral salpingo-oophorectomy: A case report and review of the literature

Intracrine oestrogen production and action in breast cancer: An epigenetic focus