Estrogen Profiles of Oriental and Caucasian Women in Hawaii

Dickinson, L; MacMahon, Brian; Cole, Philip; Brown, J. B.

doi:10.1056/nejm197412052912302

Cited by 87 publications

(15 citation statements)

References 6 publications

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“…This may explain the protective effect of early pregnancy. Consistent with this observation are also the higher rates of urinary oestriol excretion in healthy premenopausal Asiatic women with their lower risk of breast cancer compared to Caucasians [38].…”

Section: Endogenous Oestrogensupporting

confidence: 66%

Endocrine management of breast cancer—biology and current practice

Schneider

Jackisch

2005

Eur Clinics Obstet Gynaecol

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Breast cancer frequency is related to age. There are impressive advances in the diagnostic armament and surgical techniques of breast cancer, and yet, it has continued its deadly impact. In women with operable breast cancer, the histologic status of the axillary lymphnodes remains the most useful prognostic information. Today, breast cancer is viewed as a systemic disease with spreads to local and distant sites at the same time. There is a high rate of occult disease. Factors of major influence on breast cancer include reproductive experience, ovarian activity, benign breast disease, familial tendency, genetic differences, dietary considerations and specific endocrine factors. Tamoxifen still is the standard endocrine treatment for hormone-receptorpositive breast cancer both in the adjuvant and metastatic settings. Because of its weak oestrogenicity, tamoxifen may not be optimally effective and can increase the risk of endometrial cancer and stroke. Patients may also be refractory or become resistant to tamoxifen treatment. Aromatase inhibitors block the synthesis of oestrogen, have low intrinsic oestrogenic activity and, thereby, offer the potential of being more effective than tamoxifen. The challenge of the coming years is to identify women who are best treated with an aromatase inhibitor upfront rather than a tamoxifen-toaromatase inhibitor sequence. Third-generation aromatase inhibitors offer greater benefits in oestrogen receptor (ER)-positive, progesterone-negative and HER-2 overexpressing tumours. Overall, no more than 2-3% of breast cancer occurrences can be attributed to the inherited mutation of either maternal or paternal origin. Autocrine and paracrine regulation of local oestrogen biosynthesis in normal and tumour breast tissue is via growth factors acting upon aromatase activity, which is preferably expressed in the tumourbearing quadrant. Aromatase regulation operates against a concentration gradient of oestrogens, comparing peripheral plasma to local tissue levels in both premenopausal and postmenopausal women. Clinical observations suggest to routinely determine both ER subtypes and its variants, by which, the prediction of the response of the breast tumours to endocrine therapy may improve. Polymorphisms of cytochrome CYP-17, CYP-1A1 and COMT are found to be associated with an increased risk of breast cancer. To identify high-risk genotypes in women may delineate the individual at increased risk of breast cancer. Arguments in favour of an impact of postmenopausal oestrogen-progestin therapy on pre-existing tumours derive from observations in epidemiologic studies showing no increase in non-invasive breast cancer with hormone therapy; on the other hand, several studies point to a lower grade and earlier stage of disease in hormone users, with subsequently better survival rates. The older a postmenopausal woman, the greater her risk of developing an increase in breast density with hormone therapy. This is considered a good reason to recommend discontinuation of hormone therapy for at least 2 week...

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Section: Endogenous Oestrogensupporting

confidence: 66%

Endocrine management of breast cancer—biology and current practice

Schneider

Jackisch

2005

Eur Clinics Obstet Gynaecol

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“…In contrast, two studies reported lower plasma estradiol in Chinese living in Asia compared with British premenopausal women (and no racial differences in SHBG levels), although the use of age-pooled blood samples may have resulted in the inclusion of some postmenopausal women in the analyses (38,44). Finally, in three early studies, Asian women were found to have lower luteal-phase urinary estradiol levels (46)(47)(48).…”

Section: Discussionmentioning

confidence: 94%

Racial Differences in Premenopausal Endogenous Hormones

Pinheiro

Holmes

Pollak

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

104

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Differences in breast cancer incidence across racial groups are well documented. African Americans have the highest rates of premenopausal breast cancer and Asians have lower breast cancer rates across all age groups. We hypothesized that levels of premenopausal endogenous hormones and growth factors, risk factors that have been predictive of breast cancer, would differ by race. Using a cross-sectional study design, we tested this hypothesis in the Nurses' Health Study II. We assayed estradiol, progesterone, prolactin, sex hormone binding globulin (SHBG), insulin-like growth factor-I (IGF-I), and IGFBP-3 in 111 African American and 111 Asian American women, matched to 111 Caucasian women on age, day of luteal phase, and day, time, and fasting status at blood collection. We analyzed the association between race and hormone levels using robust linear regression methods. In multivariate models, compared with Caucasians, African Americans had 18% higher levels of estradiol (P < 0.01), 17% higher free estradiol (P < 0.01), 11% lower SHBG (P = 0.05), 11% higher IGF-I (P < 0.01), 25% higher free IGF-I (P < 0.01), and 9% lower IGFBP-3 (P < 0.01) levels. In multivariate models, compared with Caucasian women, Asian Americans had 22% higher calculated free estradiol (P < 0.01), 31% lower SHBG (P < 0.01), and 25% higher free IGF-I (P < 0.01) levels. No racial differences were found in progesterone and prolactin levels. Our study showed hormone differences consistent with breast cancer risk between Caucasians and African Americans but inconsistent with breast cancer risk between Asian Americans and Caucasians. Further research is needed to explore differences across racial groups and the link between endogenous hormones and breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2005;14(9):2147 -53)

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“…This hypothesis, which states that an increase in estriol formation relative to estrone and estradiol is associated with a decreased risk for the disease, was formulated both on the basis of the established protective effect of early pregnancy, a condition characterized by elevated estriol levels, and the fact that estriol was regarded as an impeded estrogen (7,29). Although some investigators provided epidemiological evidence to support this theory (30)(31)(32)(33), others reported contradictory results (10,(34)(35)(36). Moreover, a recent evaluation of estriol pharmacology has established that this steroid behaves as a potent estrogen agonist under physiological conditions (12,13,25).…”

Section: Resultsmentioning

confidence: 99%

Abnormal oxidative metabolism of estradiol in women with breast cancer.

Schneider¹,

Kinne²,

Fracchia³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

215

106

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The three dominant oxidative biotransformations of estradiol were examined in 10 normal women and 33 females with breast cancer by using a recently devised radiometric method. Estradiol tracers, labeled with 3H specifically in the 17a, C-2, or 16a position, were used to measure both the rate and extent of 17P-ol oxidation (the initial metabolic step) and the subsequent 2-and 16a-oxidative reactions. The mean ± SEM values for the extent of estradiol metabolism at these three specific sites were 76.9 ± 5.3%, 31.1 ± 4.0%, and 9.3 ± 0.8%, respectively, in normal subjects. Corresponding data in patients with breast cancer-i.e., 73.0 ± 4.2%, 32.7 ± 2.7%, and 14.9 ± 1.5%-revealed a significantly greater extent of 16a-hydroxylation in the latter population. Because the 16a-hydroxylated compounds (including estriol) are themselves potent estrogens, these changes may have important hyperestrogenic consequences that could have a bearing on the etiology of the disease.Endocrine factors have been implicated in the initiation or promotion, or both, of mammary tumorigenesis based on data collected from several sources. These include both experimental studies using animal models and epidemiological and clinical investigations in human subjects (1). Thus, certain features of the menstrual history and age at parity, which can lengthen the period ofexposure to estrogens secreted by the ovaries, appear to be associated with an increased risk for the disease (2, 3). On the other hand, oophorectomy prior to age 35 can lessen the risk of breast cancer (3). Because an augmentation in estrogen secretion could be implicated in the etiology of the human disease, numerous studies have been conducted to detect such an increase in women with, or at high risk to develop, breast cancer (4). Although some investigators have reported significant differences in urinary or plasma estrogen levels, or both, between these subjects and normal individuals (5-7), these findings have not been consistent and have been challenged by others (8, 9). An alternative and possibly more viable hypothesis that an alteration in estrogen metabolism is associated with breast cancer (4, 10) has also been the subject of extensive investigations.The metabolism of estradiol, which is primarily oxidative, consists ofan initial oxidation ofthe 17/3-hydroxy group to yield estrone. This steroid is subsequently metabolized mainly through either of two alternate hydroxylative pathways; namely, hydroxylation at the C-2 or the 16a position (11). These hydroxylations are of particular interest in that they constitute competing reactions whose products are themselves active compounds characterized by markedly different biological properties. The 16a-hydroxyestrogens-estriol and 16a-hydroxyestrone-demonstrate uterotropic activity comparable to that of the parent hormone, estradiol (12, 13). On the other hand, the principal 2-hydroxyestrogens-2-hydroxyestrone and 2-methoxyestrone exhibit virtually no peripheral estrogenic effects but appear to play a regulatory role in neur...

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Estrogen Profiles of Oriental and Caucasian Women in Hawaii

Cited by 87 publications

References 6 publications

Endocrine management of breast cancer—biology and current practice

Endocrine management of breast cancer—biology and current practice

Racial Differences in Premenopausal Endogenous Hormones

Abnormal oxidative metabolism of estradiol in women with breast cancer.

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