Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition

Kaaks, Rudolf; Rinaldi, Sabina; Key, Timothy J.; Berrino, Franco; Peeters, Petra H.M.; Biessy, Carine; Dossus, Laure; Lukanova, Annekatrin; Bingham, Sheila; Khaw, K-T; Allen, Naomi E.; Bueno‐de‐Mesquita, H. Bas; Gils, Carla H. van; Grobbee, Diederick E.; Boeing, Heiner; Lahmann, Petra H.; Nagel, Gabriële; Chang‐Claude, Jenny; Clavel‐Chapelon, Françoise; Fournier, Agnès; Thiébaut, Anne C. M.; González, Carlos; Quiŕos, J. Ramón; Tormo, MJ; Ardanáz, Eva; Amiano, Pilar; Krogh, Vittorio; Palli, Domenico; Panico, Salvatore; Tumino, Rosario; Víneis, Paolo; Trichopoulou, Antonia; Kalapothaki, V.; Trichopoulos, D.; Ferrari, Pietro; Norat, Teresa; Saracci, Rodolfo; Riboli, Elio

doi:10.1677/erc.1.01038

Cited by 468 publications

(385 citation statements)

References 49 publications

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“…An analysis of worldwide prospective studies showed strong associations of testosterone and DHEAS with breast cancer risk in postmenopausal women (58). Similar conclusions were obtained from a casecontrol study (59) and a large multicentric cohort study (60). A recent study has shown that high circulating levels of total and free testosterone are associated with the risk of developing breast cancer in postmenopausal women, while circulating estradiol level is not associated with the risk of breast cancer (61).…”

Section: Endogenous Androgen and Breast Cancer In Womensupporting

confidence: 77%

Androgen in postmenopausal women

et al. 2012

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Dynamic changes in circulating estradiol level, including increase at menarche and decrease at menopause, occur in a woman's lifetime. Circulating estradiol levels decrease drastically during the menopausal transition, though the levels differ among races. It has been reported that estradiol levels in both Japanese and Chinese women were lower than those in Caucasians, Hispanic and AfricanAmericans (1).Based on data obtained in a previous study (2), we re-analyzed data for 169 healthy men and 252 healthy women aged from 40 to 85 years in the population-based study with addition of data for premenopausal women. Change in circulating estradiol in women from the menopausal transition to postmenopause is characterized as follows : high estradiol level in premenopausal women is drastically decreased and estradiol level in postmenopausal women is significantly lower than that in agematched men. Mean estradiol levels were shown to be 20.1 pg/ml in men and 6.1 pg/ml in postmenopausal women (Figure 1). This dynamic decrease in REVIEW Androgen in postmenopausal women

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Section: Endogenous Androgen and Breast Cancer In Womensupporting

confidence: 77%

Androgen in postmenopausal women

et al. 2012

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“…Although the associations of endogenous sex hormone levels with the risk of breast cancer overall, all subtypes combined, are well established (9,10), only few prospective studies have thus far investigated this association by hormone receptor status (2,(11)(12)(13)(14)(15). In the latter studies, estradiol and testosterone levels have shown direct relationships with ER-positive, PR-positive, and joint ERþPRþ tumors (14,15).…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, prospective studies investigating associations with hormone receptor-negative or HER2-positive breast cancer have been limited by relatively small numbers of ER-negative tumors (14,15). Previously, the relationship between postmenopausal sex steroid hormone and sex hormone binding-globulin (SHBG) levels with breast cancer risk overall was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (10). The current analysis expands on this nested case-control study with additional breast cancer cases, with a particular focus on receptor status and with oversampling of ER-negative cases.…”

Section: Introductionmentioning

confidence: 99%

Postmenopausal Serum Sex Steroids and Risk of Hormone Receptor–Positive and -Negative Breast Cancer: a Nested Case–Control Study

James

Lukanova

Dossus

et al. 2011

Cancer Prevention Research

116

113

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Prediagnostic endogenous sex steroid hormone levels have well established associations with overall risk of breast cancer. While evidence toward the existence of distinct subtypes of breast cancer accumulates, few studies have investigated the associations of sex steroid hormone levels with risk of hormone receptor [estrogen receptor (ER) and/or progesterone receptor (PR)] defined breast cancer. In a case-control study nested within the EPIC cohort (European Prospective Investigation into Cancer and Nutrition), estradiol, testosterone, and sex hormone-binding globulin levels were measured in prediagnostic serum samples from postmenopausal women not using hormone replacement therapy at blood donation. A total of 554 women who developed invasive breast cancer with information on receptor status were matched with 821 control subjects. Conditional logistic regression models estimated breast cancer risk with hormone concentrations according to hormone receptor status of the tumor. Sex steroid hormones were associated with risks of not only ERþPRþ breast cancer [estradiol OR for highest vs. lowest tertile ¼ 2.91 (95% CI: 1.62-5.23), P trend ¼ 0.002; testosterone OR ¼ 2.27 (95% CI: 1.35-3.81), P trend ¼ 0.002] but also of ER-PR-breast cancer [estradiol OR ¼ 2.11 (95% CI: 1.00-4.46), P trend ¼ 0.05; testosterone OR ¼ 2.06 (95% CI: 0.95-4.46), P trend ¼ 0.03], with associations appearing somewhat stronger in the receptor-positive disease. Serum androgens and estrogens are associated with risks of both hormone receptor-negative as well as receptor-positive breast tumors. Further research is needed to establish through which molecular pathways, and during which evolutionary stages of development, androgens and estrogens can promote the occurrence of both receptor-positive and -negative clinical breast tumors. Cancer Prev Res; 4(10); 1626-35. Ó2011 AACR.

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“…[2][3][4][5][6][7] Prolactin levels have also been found to be positively associated with breast cancer risk among postmenopausal women, 8,9 while high sex hormone binding globulin (SHBG) levels have been associated with a decreased risk of breast cancer. 2,6 Mammographic density is one of the strongest independent risk factors for breast cancer, [10][11][12] and possibly an intermediate marker for breast cancer. 13 Women with high mammographic density have a 4-to 6-fold increase in breast cancer risk compared with women with low mammographic density.…”

mentioning

confidence: 99%

Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women

Bremnes

Ursin

Bjurstam

et al. 2007

Intl Journal of Cancer

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The associations between endogenous sex hormone levels and breast cancer risk in postmenopausal women are well established. Mammographic density is a strong risk factor for breast cancer, and possibly an intermediate marker. However, the results from studies on the associations between endogenous sex hormones and mammographic density are conflicting. The authors examined the associations between circulating levels of sex hormones, sex hormone binding globulin (SHBG) and prolactin and mammographic densities among postmenopausal women not currently using postmenopausal hormone therapy (HT). The authors also examined if insulin-like growth factor-I (IGF-I) levels influenced the association between estrogen and mammographic density. Altogether, 722 postmenopausal participants in the Norwegian governmental mammographic screening program had endogenous hormone concentrations measured. Mammograms were classified according to percent and absolute mammographic density using a previously validated computer-assisted method. After adjustment for age, number of children, age at menopause, body mass index and HT use, both plasma concentrations of SHBG (p-trend 5 0.003) and estrone (p-trend 5 0.07) were positively associated with percent mammographic density. When the analyses were stratified according to median IGF-I concentration, the weak association between estrone and mammographic density was strengthened among women with IGF-I levels below median, while the association disappeared among women with over median IGF-I levels (p for interaction 5 0.02). In summary, the authors found a positive association between plasma SHBG levels and mammographic densities among 722 postmenopausal Norwegian women not currently using HT. Further, the authors found a positive but weak association between plasma estrone concentration and mammographic density, which appeared to be modified by IGF-I levels. ' 2007 Wiley-Liss, Inc.Key words: mammography; breast density; sex hormones; prolactin; postmenopausal; breast cancer Several breast cancer risk factors (e.g., age, age at menarche, parity, age at menopause) are believed to be related to the cumulative exposure of the breast tissue to endogenous hormonal substances. 1 Prospective studies have shown that circulating levels of sex hormones are associated with an increased risk of breast cancer in postmenopausal women not currently using postmenopausal hormone therapy (HT). 2-7 Prolactin levels have also been found to be positively associated with breast cancer risk among postmenopausal women, 8,9 while high sex hormone binding globulin (SHBG) levels have been associated with a decreased risk of breast cancer. 2,6 Mammographic density is one of the strongest independent risk factors for breast cancer, 10-12 and possibly an intermediate marker for breast cancer. 13 Women with high mammographic density have a 4-to 6-fold increase in breast cancer risk compared with women with low mammographic density. [10][11][12] The 6 studies published so far on the association between endogenous sex hormones a...

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Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition

Cited by 468 publications

References 49 publications

Androgen in postmenopausal women

Androgen in postmenopausal women

Postmenopausal Serum Sex Steroids and Risk of Hormone Receptor–Positive and -Negative Breast Cancer: a Nested Case–Control Study

Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women

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