Research table: Blood estrogen levels and breast cancer risk

This summary table contains detailed information about research studies. Summary tables are a useful way to look at the science behind many breast cancer guidelines and recommendations. However, to get the most out of the tables, it’s important to understand some key concepts. Learn how to read a research table.

Introduction: Estrogens are natural hormones. They are important in sexual development and other body functions. Before menopause, they are produced mainly in the ovaries. After menopause, they are produced mainly in fat tissue.

Women have different sources (and different levels) of estrogen before and after menopause. So, it’s important to look at studies of estrogen and breast cancer risk by menopausal status.

Breast cancer risk after menopause

Studies show higher blood levels of the estrogen called estradiol are linked to an increased risk of breast cancer in postmenopausal women.

Menopausal hormone therapy

The studies below excluded women taking menopausal hormone therapy (MHT) at the time of blood collection. MHT is FDA-approved for the short-term relief of menopausal symptoms. MHT is also called postmenopausal hormone therapy or hormone replacement therapy (HRT).

Women who use MHT have an increased risk of breast cancer. This increased breast cancer risk related to MHT may make it difficult to see a link between natural blood estrogen levels and breast cancer risk in study data. By looking only at women who don’t take (or who have never taken) MHT, researchers may see more clearly how blood estrogen levels are related to breast cancer risk.

Breast cancer risk before menopause

A pooled analysis of data from 7 studies found higher blood estrogen levels are linked to an increased risk of breast cancer in premenopausal women [1].

Learn more about blood estrogen levels and breast cancer risk.

Learn about 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: Prospective nested case-control studies with at least 100 breast cancer cases, pooled analyses and meta-analyses.

Table note: Relative risks above 1 indicate increased risk. Relative risks below 1 indicate decreased risk.

This table shows breast cancer risk related to total estradiol levels.

Study	Study Population (number of participants)		Risk of Breast Cancer in Women with Higher Estradiol Levels Compared to Women with Lower Estradiol Levels Relative Risk (95%CI)
			Before Menopause	After Menopause
Nested case-control studies
	Cases	Controls
Nurses’ Health Study [2]	707	1,414		2.1 (1.6-2.7)*
EPIC cohort [3-4]	554	821		2.58 (1.69-3.93)†
	285	555	1.00 (0.66-1.52)‡
New York University Women’s Health Study [5]	297	563		2.06 (1.18-3.60)
PLCO [6]	277	423		1.75 (1.03-2.98)
Nurses’ Health Study II [7]	221	677	1.2 (1.0-1.4)§
Falk et al. [8]	215	215		1.13 (0.63-2.01)
UK Collaborative Trial of Ovarian Cancer Screening [9]	200	400		1.15 (0.67-2.00)
Melbourne Collaborative Cohort Study [10]	197	857		1.44 (0.89-2.35)||
Study of Osteoporosis Fractures Research Group [11-12]	196	378		1.8 (0.9-3.6)¶
	97	242		2.9 (1.2-7.2)
ORDET cohort [13-14]	165	642		1.50 (0.88-2.54)
	104	225	0.69 (0.35-1.35)**
Pooled and meta-analyses
	Cases	Controls
EHBCCG [1,15]	767	1,699	1.41 (1.02-1.95)
	663	1,765		2.00 (1.47-2.71)
Walker et al. [16]	693	1,609	1.14 (0.98-1.32)
Manjer et al. [17]	173	438		1.73 (1.04-2.88)

* Relative risk for estrogen receptor-positive and progesterone receptor-positive breast cancers was 2.8 (2.0-4.0). Relative risk for estrogen receptor-negative and progesterone receptor-negative (ER-negative/PR-negative) breast cancers was 1.1 (0.6-2.1).

† Relative risk for estrogen receptor-positive cancers. Relative risk for estrogen receptor-negative breast cancers was 1.65 (0.91-2.98).

‡ Results are for estradiol blood levels measured in the follicular phase of the menstrual cycle. Results for estradiol levels measured in the luteal phase of the menstrual cycle were not statistically significant.

§ Results are for estradiol blood levels measured in the follicular phase of the menstrual cycle. Results for estradiol levels measured in the luteal phase were similar with a relative risk of 1.2 (1.0-1.6).

|| Relative risk for women with higher levels of free estradiol compared to women with lower levels of free estradiol was 1.75 (1.06-2.89).

¶ Relative risk for estrogen receptor-positive cancers. Authors noted an increase in risk before adjustment for blood testosterone levels.

** Results are for estradiol blood levels measured in the luteal phase of the menstrual cycle.

References

1. Endogenous Hormones and Breast Cancer Collaborative Group. Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies. Lancet Oncol. 14(10):1009-19, 2013.
2. Zhang X, Tworoger SS, Eliassen AH, Hankinson SE. Postmenopausal plasma sex hormone levels and breast cancer risk over 20 years of follow-up. Breast Cancer Res Treat. 137(3):883-92, 2013.
3. James RE, Lukanova A, Dossus L, et al. Postmenopausal serum sex steroids and risk of hormone receptor-positive and -negative breast cancer: a nested case-control study. Cancer Prev Res (Phila). 4(10):1626-35, 2011.
4. 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.
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. Fuhrman BJ, Schairer C, Gail MH, et al. Estrogen metabolism and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 104(4):326-39, 2012.
7. Fortner RT, Eliassen AH, Spiegelman D, Willett WC, Barbieri RL, Hankinson SE. Premenopausal endogenous steroid hormones and breast cancer risk: results from the Nurses’ Health Study II. Breast Cancer Res. 15(2):R19, 2013.
8. Falk RT, Brinton LA, Dorgan JF, et al. Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested case-control study. Breast Cancer Res. 15(2):R34, 2013.
9. Fourkala EO, Zaikin A, Burnell M, et al. Association of serum sex steroid receptor bioactivity and sex steroid hormones with breast cancer risk in postmenopausal women. Endocr Relat Cancer. 19(2):137-47, 2012.
10. Baglietto L, Severi G, English DR, et al. Circulating steroid hormone levels and risk of breast cancer for postmenopausal women. Cancer Epidemiol Biomarkers Prev. 19(2):492-502, 2010.
11. 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.
12. 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.
13. Sieri S, Krogh V, Bolelli G, et al. Sex hormone levels, breast cancer risk, and cancer receptor status in postmenopausal women: the ORDET cohort. Cancer Epidemiol Biomarkers Prev. 18(1):169-76, 2009.
14. Schernhammer ES, Sperati F, Razavi P, et al. Endogenous sex steroids in premenopausal women and risk of breast cancer: the ORDET cohort. Breast Cancer Res. 15(3):R46, 2013.
15. Walker K, Bratton DJ, Frost C. Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis. Br J Cancer. 105(9):1451-7, 2011.
16. 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.
17. 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.