This summary table contains detailed information about research studies. While viewing summary tables offers an informative glimpse at the science behind many breast cancer guidelines and recommendations, they should be viewed with some caution. There are a number of concepts you must understand to be able to successfully read and interpret research tables. To get some background information about understanding research tables, please see How to Read a Research Table.
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Introduction: Estrogens are natural hormones that are important in sexual development and other body functions. Estrogens are produced mainly in the ovaries in premenopausal women, and mainly in fat tissue in postmenopausal women. Higher amounts of estrogen in the blood are linked to an increased risk of breast cancer in postmenopausal women. Researchers are studying a possible link to breast cancer among premenopausal women as well.
Because of the different sources (and different levels) of estrogen in premenopausal and postmenopausal women, it is important to look at studies of blood estrogen and breast cancer risk by menopausal status. The studies listed below show that higher blood levels of the estrogen, estradiol, increase the risk of breast cancer in postmenopausal women. Notably, all of these studies excluded women who were using postmenopausal hormones at the time of blood collection. Certain postmenopausal hormones might mask the full effect that natural blood estrogen levels have on breast cancer risk. By looking only at women who are not taking (or who have never taken) postmenopausal hormones, researchers may see more clearly how blood estrogen levels affect breast cancer risk.
In postmenopausal women, higher body weight is related to higher levels of estrogen in the body [1]. It appears that among heavier women the link between body weight and breast cancer is at least in part due to these higher estrogen levels [2]. While this biological process is still under study, changes in body weight can affect blood estrogen levels, which may in turn affect breast cancer risk. Maintaining a healthy weight may lower breast cancer risk through several mechanisms in the body.
Few studies have looked at blood estrogen levels and breast cancer risk in premenopausal women. In the only two large studies to date, findings were mixed. Studies in premenopausal women are more difficult to do because estrogen levels vary so much over the menstrual cycle. For example, estrogen levels are much lower in the early phase (follicular) than the late phase (luteal) of the menstrual cycle.
Find more information on the strengths and weaknesses of different types of studies.
See how this risk factor compares with other risk factors for breast cancer.
Study selection criteria: Available prospective nested case-control studies and pooled analyses with at least 75 cases.
Table note: Odds ratios above 1 indicate increased risk. Odds ratios below 1 indicate decreased risk. Risks related to total estradiol levels are shown in this table. Although free estradiol may more strongly related to breast cancer risk than total estradiol, many studies did not measure free estradiol. Therefore, data on free estradiol levels and breast cancer risk are more limited at this time.
Study
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Study Population
(number of participants)
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Risk of Breast Cancer in Women with Higher Estradiol Levels Compared to Women with Lower Estradiol Levels,
Odds Ratio (95%CI)
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Premenopausal
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Postmenopausal
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Nested case-control studies
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Cases
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Controls
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Nurses' Health Study [3,4]
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322
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643
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2.1 (1.5-3.2)*
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New York University Women's Health Study [5]
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297
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563
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2.06 (1.18-3.60)
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EPIC [6,7]
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285
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555
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1.00 (0.66-1.52)†
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2.28 (1.61-3.23)
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Nurses' Health Study II [8]
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197
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394
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2.7 (1.3-5.4)
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Study of Osteoporosis Fractures Research Group [9,10]
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196
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378
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1.8 (0.9-3.6)‡
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97
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242
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2.9 (1.2-7.2)
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Pooled analyses
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Cases
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Controls
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EHBCCG [11]
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663
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1,765
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2.00 (1.47-2.71)
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Manjer et al. [12]
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173
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438
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1.73 (1.04-2.88)
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* Among women using postmenopausal hormones, there was no increase in overall risk of breast cancer for women with higher blood estrogen levels. However, among postmenopausal hormone users with higher estrogen levels, there was a modest increase in the risk of ER+/PR+ breast cancers.
† High versus low levels of estradiol in women at the same point in their menstrual cycle. Results for follicular estradiol levels. Results for luteal estradiol levels were not statistically significant.
‡ Relative risk for ER+ cancers only. Authors noted a significant increase in risk before adjustment for blood testosterone levels.
References
1. van den Brandt PA, Spiegelman D, Yan SS. Et al. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 152(6):514-27, 2000.
2. Key TJ, Appleby PN, Reeves GK, et al. for the Endogenous Hormones Breast Cancer Collaborative Group. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst. 95(16):1218-26, 2003.
3. Missmer SA, Eliassen AH, Barbieri RL, Hankinson SE. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J Natl Cancer Inst. 96(24):1856-65, 2004.
4. Tworoger SS, Missmer SA, Barbieri RL, Willett WC, Colditz GA, Hankinson SE. Plasma sex hormone concentrations and subsequent risk of breast cancer among women using postmenopausal hormones. J Natl Cancer Inst. 97(8):595-602, 2005.
5. Zeleniuch-Jacquotte A, Shore RE, Koenig KL, Akhmedkhanov A, Afanasyeva Y, Kato I, Kim MY, Rinaldi S, Kaaks R, Toniolo P. Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study. Br J Cancer. 90(1):153-9, 2004.
6. Kaaks R, Berrino F, Key T, et al. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst. 97(10):755-65, 2005.
7. Kaaks R, Rinaldi S, Key TJ, et al. Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer. 12(4):1071-82, 2005.
8. Eliassen AH, Missmer SA, Tworoger SS, et al. Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst. 98(19):1406-15, 2006.
9. Cummings SR, Lee JS, Lui LY, Stone K, Ljung BM, Cauleys JA, for the Study of Osteoporosis Fractures Research Group. Sex hormones, risk factors, and risk of estrogen receptor-positive breast cancer in older women: a long-term prospective study. Cancer Epidemiol Biomarkers Prev. 14(5):1047-51, 2005.
10. Cauley JA, Lucas FL, Kuller LH, et al. Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Ann Intern Med. 130(4):270-277, 1999.
11. The Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 94(8): 606-616, 2002.
12. Manjer J, Johansson R, Berglund G, Janzon L, Kaaks R, Agren A, Lenner P. Postmenopausal breast cancer risk in relation to sex steroid hormones, prolactin and SHBG (Sweden). Cancer Causes Control. 14(7):599-607, 2003.
Updated 09/04/09
