Influence of Intratumoral Estradiol Biosynthesis on Estrogen Receptors

Carlström, Kjell

doi:10.1007/978-3-642-82188-2_20

Cited by 15 publications

(4 citation statements)

References 16 publications

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“…6 Furthermore, it is worth noting that, in our study, reverse causation, that is, changes in estrogen receptor status by factors generated by the tumor itself, can safely be excluded, since no biopsy from breast cancer was included in the study. 18 Even though, as indicated, the results are only in the margin of significance, they acquire credibility from the fact that the working hypothesis explicitly postulated a higher expression of estrogen receptor ␣ among women at higher risk for breast cancer. The hypothesis is also supported by the results of several independent investigations that have shown an increase in the level of estrogen receptor ␣ expression as mammary histology progresses from normal to proliferative to carcinoma in situ and eventually invasive carcinoma 6,7 and by a report from a case-control study that the likelihood of breast cancer increases when there is overexpression of estrogen receptors in the normal epithelium.…”

Section: Discussionmentioning

confidence: 94%

Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii

Lawson

Field

Tran

et al. 2001

Intl Journal of Cancer

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We have undertaken a study to examine whether the difference in breast cancer incidence between 2 populations of similar genetic background is reflected in a similar pattern of estrogen receptor ␣ expression in normal mammary gland. Study participants were 92 Japanese women from Sapporo, Japan (mean age 48.2 years) and 49 Japanese women from Honolulu, Hawaii (mean age 45.4 years), who underwent biopsy indicating normal breast tissue or benign, nonproliferative breast disease in hospitals in Sapporo, Japan and Honolulu, Hawaii. The breast tissue samples were formalin-fixed and paraffin-embedded. The estrogen receptor immunohistochemistry assays were conducted using Dako kits. Japanese women in Hawaii, who have a higher incidence of breast cancer compared with Japanese women in Sapporo, also had, as predicted, higher mean percentage of estrogen receptor ␣-positive normal mammary cells (2-tailed test, p ϳ 0.09). The results of our study are compatible with the hypothesis that estrogen receptor ␣ expression in normal mammary tissue increases breast cancer risk and they also indicate that the expression of these receptors is dependent, at least in part, on nongenetic factors. © 2002 Wiley-Liss, Inc. Key words: breast cancer; estrogen receptors; epidemiology; Japanese Endogenous estrogens are central in the etiology of breast cancer in women. [1][2][3][4] Nevertheless, no aspect of estrogen production, metabolism and physiologic effects can fully explain the higher incidence of the disease among Caucasian women in North America, northern Europe or Oceania in comparison with Japanese and Chinese women in their home countries. 5 Because estrogen receptors are mandatory for estrogen response, it has been hypothesized that expression of these receptors in normal breast tissue could be as important as estrogen levels for the determination of breast cancer risk. 6 -9 In a recent paper, we have reported that expression of estrogen receptor ␣ is much higher among Australian Caucasian women than among Japanese women in Japan, in parallel with the much higher breast cancer incidence among the former compared with the latter. 10 The incidence of breast cancer among Japanese women in Hawaii is at least twice as high as that among Japanese living in Japan, although not quite as high as the incidence of breast cancer among Caucasians. 5 This is a well-established pattern for migrants from low to high breast cancer risk countries and their descendants. 11-13 Indeed, this pattern has been used to argue that a large fraction of the variation of breast cancer incidence in women is of exogenous, rather than genetic, etiology. We undertook a study to examine whether the higher breast cancer incidence of Japanese in Hawaii in comparison with Japanese in Japan is reflected in a similar pattern of estrogen receptor ␣ expression in normal mammary gland. This, if detected, would support the hypothesis that the expression of these receptors in normal breast is a risk factor for breast cancer and would also indicate that the expression of t...

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Section: Discussionmentioning

confidence: 94%

Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii

Lawson

Field

Tran

et al. 2001

Intl Journal of Cancer

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“…Although the main estrogenic activity in postmenopausal women has been attributed to estrone [25] and estrone sulfate [26], and A4-dione is considered the main precursor of these estrogens, no information was previously available on the action of this steroid in estrogen-sensitive breast cancer models. The present data show that A4-dione, at concentrations within the range of those found in adult women, is also a potent stimulus of DMBAinduced tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Androstenedione and androst-5-ene-3β,17β-diol stimulate DMBA-induced rat mammary tumors — role of aromatase

Dauvois

Labrie

1989

Breast Cancer Res Tr

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The effect of the adrenal steroids androst-5-ene-3 beta,17 beta-diol (delta 5-diol) and androstenedione (delta 4-dione) was studied on the growth of mammary carcinoma induced in the rat by dimethylbenz[a]anthracene (DMBA). The plasma levels of the two steroids were maintained at values within the range of those found in the circulation of post-menopausal women by constant release from osmotic pumps in ovariectomized animals. delta 5-diol and delta 4-dione, at the daily release rate of 500 micrograms, led to plasma levels of 1.26 +/- 0.19 and 1.72 +/- 0.75 ng/ml, respectively. At these physiologically relevant plasma concentrations, both delta 5-diol and delta 4-dione caused a marked stimulation of tumor growth while having minimal or no effect on uterine weight or on plasma prolactin and LH levels. Concomitant treatment with the aromatase inhibitor aminoglutethimide completely blocked the stimulatory effect of delta 4-dione released from silastic implants on tumor growth, while simultaneous administration of the antiandrogen flutamide had no significant effect. On the other hand, when aminoglutethimide was administered with delta 5-diol, the stimulatory effect of the adrenal steroid on tumor growth was not affected. Such data indicate that, under the present experimental conditions, transformation of delta 4-dione into androgens plays a minor role, the predominant effect of the adrenal steroid being stimulation of tumor growth through conversion into estrogens, while delta 5-diol exerts a direct estrogenic effect independent from aromatase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…There is considerable work indicating that there are differences in enzymatic (aromatase, sulfatase, and dehy drogenase) activity in tumor-bearing regions of the breast [25][26][27][28][29][30], There are two possible explanations for these Regional Proliferation and Steroid Receptors in the Macaque Breast findings: either tumors secrete factors capable of enhanc ing enzymatic activity, or conversely increased enzymatic activity in a particular quadrant results in a local environ ment which encourages tumor development at that site. The present data indicate that these changes are likely to be secondary to tumor development rather than being preexisting differences.…”

Section: Discussionmentioning

confidence: 99%

Regional Distribution of Proliferating Cells and Hormone Receptors in the Mammary Gland of Surgically Postmenopausal Macaques

Söderqvist

et al. 1997

Gynecol Obstet Invest

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Objective: To define the relative proliferative response and hormone receptors status in ten sites in the mammary gland of surgically postmenopausal cynomolgus macaques given hormone replacement therapy. Methods: Surgical postmenopausal cynomolgus macaques were given either no treatment (n = 4), conjugated equine estrogens (CEE, n = 4), or combined therapy with CEE and medroxyprogesterone acetate (n = 4). The drugs were administered in the diet, at doses equivalent on a caloric basis to 0.625 mg/woman/day for CEE and 2.5 mg/woman/day for medroxyprogesterone acetate. Immunostaining of mammary sections was done for estrogen receptor, progesterone receptor, and the proliferation marker Ki-67 MIB-1 (MIB). Comparisons were made between central and peripheral gland, by quadrant, left versus right, and with respect to distance from the nipple within each quadrant. Result: There were no significant differences in hormone receptor or MIB expression within different sites within the gland. Conclusions: In the surgically postmenopausal, hormone-treated macaque, regional differences in estrogen and progesterone receptors and MIB staining are not apparent. The assumption of homogeneity throughout the gland makes aspiration cytology and multiple biopsy studies feasible in this species.

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Influence of Intratumoral Estradiol Biosynthesis on Estrogen Receptors

Cited by 15 publications

References 16 publications

Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii

Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii

Androstenedione and androst-5-ene-3β,17β-diol stimulate DMBA-induced rat mammary tumors — role of aromatase

Regional Distribution of Proliferating Cells and Hormone Receptors in the Mammary Gland of Surgically Postmenopausal Macaques

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