Abstract
High levels of serum estrogens and androgens have been convincingly linked with an increased risk of breast cancer among postmenopausal women. By contrast, the role of blood levels of these hormones in the etiology of premenopausal breast cancer is not well understood. In a case–control study, we sought to examine associations between levels of serum estradiol, sex-hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), testosterone, androstenedione and progesterone and risk of premenopausal breast cancer. Cases of breast cancer under age 45 were identified using rapid ascertainment systems in Seattle/Puget Sound, Washington and control subjects were identified from the same area through random digit dialing methods. A total of 169 eligible breast cancer cases and 195 control subjects donated blood (either before or six or more weeks after surgery) and were interviewed using a standardized questionnaire. The fully adjusted risk ratios and 95% confidence intervals for the highest versus lowest tertiles of estradiol, according to menstrual cycle phase, were 3.10 (0.8–12.7) for early follicular, 0.54 (0.2–1.7) for late follicular and 0.60 (0.3–1.4) for luteal. Risks for highest versus lowest quartiles of SHBG and androgens were 0.81 (0.4–1.6) for SHBG, 2.42 (1.1–5.2) for DHEA, 1.12 (0.6–2.5) for testosterone, and 1.33 (0.6–2.8) for androstenedione. For luteal progesterone, the RR for the highest versus lowest tertile was 0.55 (0.2–1.4). In summary, we did not find a convincing association between serum SHBG, estradiol, testosterone or androstenedione and premenopausal breast cancer risk. Observed differences between cases and controls subjects in serum levels of DHEA and luteal phase progesterone should be investigated further in large prospective studies.
Similar content being viewed by others
References
The Endogenous Hormones and Breast Cancer Collaborative Study (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective cohort studies. J Natl Cancer Inst 94: 606-616.
Key TJ, Verkasalo PK (1999) Endogenous hormones and the aetiology of breast cancer. Breast Cancer Res 1: 18-21.
Key TJA, Pike MC (1988) The role of oestrogens and progestagen. Epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 24: 29-43.
Wysowski DK, Comstock GW, Helsing KJ, Lau HL (1987) Sex hormone levels in serum in relation to the development of breast cancer. Am J Epidemiol 125: 791-799.
Helzlsouer KJ, Alberg AJ, Bush TL, Longcope C, Gordon GB, Comstock GW (1994) A prospective study of endogenous hormones and breast cancer. Cancer Detect Prev 18: 79-85.
Rosenberg CR, Pasternack BS, Shore RE, Koenig KL, Toniolo PG (1994) Premenopausal estradiol levels and the risk of breast cancer: a new method of controlling for day of the menstrual cycle. Am J Epidemiol 140: 518-525.
Thomas HV, Key TJ, Allen DS, et al. (1997) A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey. Br J Cancer 75: 1075-1079.
The Ango-Egyption Health Agreement Collaborative Study (1988) Serum hormone levels in breast cancer patients in Egypt and Great Britain. Eur J Cancer Clin Oncol 21: 1329-1335.
Bernstein L, Yuan JM, Ross RK, et al. (1990) Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles: results from two breast cancer case-control studies. Cancer Causes Control 1: 51-58.
Zaridze D, Kushlinskii, Moore JW, Lifanova Y, Bassalyk L,Wang DY (1992) Endogenous plasma sex hormones in pre-and postmenopausal women with breast cancer: results from a case-control study in Moscow. Eur J Cancer Prev 1: 225-230.
Malarkey WB, Schroeder LL, Sevens VC, James AG, Lanese RR (1977) Twenty-four-hour preoperative endocrine profiles in women with benign and malignant breast disease. Cancer Res 37: 3655-4639.
Helzlsouer KJ, Gordon GB, Alberg AJ, Bush TL, Comstock GW (1992) Relationship of prediagnostic serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing premenopausal breast cancer. Cancer Res 52: 1-4.
Secreto G, Toniolo P, Berrino F, et al. (1984) Increased androgenic activity and breast cancer risk in premenopausal women. Cancer Res 44: 5902-5905.
Secreto G, Toniolo P, Pisani P, et al. (1989) Androgens and breast cancer in premenopausal women. Cancer Res 49: 471-476.
Secreto G, Recchione C, Fariselli G, DiPietro S (1984) High testosterone and low progesterone circulating levels in premenopausal patients with hyperplasia and cancer of the breast. Cancer Res 44: 841-844.
Zumo. B, Levin J, Rosenfeld RS, Markham M, Strain GW, Fukushima DK (1981) Abnormal 24-hr mean plasma concentrations of dehydroisoandrosterone and dehydroisoandrosterone sulfate in women with primary operable breast cancer. Cancer Res 41: 3360-3363.
Weiss HA, Brinton LA, Brogan D, et al. (1996) Epidemiology of in situ and invasive breast cancer in women aged under 45. Br J Cancer 73: 1298-1305.
Abraham GE, Odell WD, Swerdloff RS, Hopper K (1972) Simultanoues radioimmunoassay of plasma FSH, LH, progesterone, 17-hydroxyproigesterone, and estradiol-17 beta during the menstrual cycle. J Clin Endocrinol Metab 34: 312-318.
Erickson GF (1987) The ovary: basic principles and concepts. In: Felig P, Baxter JD, Broadus AE, Frohman LA, eds. Endocrinology and Metabolism, 2nd edn. New York (NY): McGraw-Hill Book Company, pp. 905-983.
Van Cauter E, Copinschi G, Turek FW (2001) Endocrine and other biologic rhythms. In: De Groot LJ, Jameson JL, eds. Endocrinology, 4th edn. Philadelphia: WB Saunders, pp. 235-256.
Michaud DS, Manson JE, Spiegelman D, et al. (1999) Reproducibility of plasma and urinary sex hormone levels in premenopausal women over a one-year period. Cancer Epidemiol Biomar Prev 8: 1059-1064.
Boccuzzi G, Aragno M, Brignardello E et al. (1992) Opposite effects of dehydroepandrosterone on the growth of 7,12-dimethylbenz( a)anthracene-induced rat mammary carcinomas. Anticancer Res 12: 1479-1484.
Adams J, Garcia M, Rochefort H (1990) Estrogenic effect of physiological concentrations of 5-androstene-3 B,17 B-diol and its metabolism in MCF7 human breast cancer cells. Oncology 47: 269-274.
Najid A, Habrioux G (1990) Biological effects of adrenal androgens on MCF-7 and BT-20 human breast cancer cells. Oncology 47: 269-274.
Boccuzzi G, Brignardello E, Di Monaco M, Forte C, Leonardi L, Pizzini A (1992) Influence of dehydroepiandrosterone and 5-enandrostene-3-beta,17 beta-diol on the growth of MCF-7 human breast cancers induced by 17 beta-estradiol. Anticancer Res 12: 79-803.
Boccuzzi G, Bridnardello E, DiMonaco M, et al. (1997) 5-ENandrostene-3b,17B-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol Br J Cancer 70: L1035-L1039.
Lindh A, Carlstrom K, Eklund J, Wilking N (1992) Serum steroids and prolactin during and after major surgical trauma. Acta Anaesthesiol Scand 36: 119-124.
Stoll BA (1999) Dietary supplements of dehydroepiandrosterone in relation to breast cancer risk. Eur J Clin Nutr 53: 771-775.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sturgeon, S.R., Potischman, N., Malone, K.E. et al. Serum levels of sex hormones and breast cancer risk in premenopausal women: a case–control study (USA). Cancer Causes Control 15, 45–53 (2004). https://doi.org/10.1023/B:CACO.0000016574.79728.11
Issue Date:
DOI: https://doi.org/10.1023/B:CACO.0000016574.79728.11