Abstract
Between 1961 and 1967 a cohort of over 5000 women volunteered for a prospective study to determine the relationship between the urinary androgen metabolites, androsterone (A) and aetiocholanolone (E), and risk of breast cancer. During the first 10 years of the study the concentration of urinary A and E was determined in 1887 of the urine specimens. In 1971 we reported that subnormal amounts of urinary A and E were associated with a significantly increased risk of breast cancer. The cohort has been followed regularly during the 37 years since inception of the study and, by May 1998, 248 women had been diagnosed with breast cancer. Urinary androgen metabolites had been measured in 116 of these cases. Analysis of these data confirmed that women diagnosed in the first decade of the study were more likely to have low levels of urinary androgen metabolites. In the following decades, however, those who developed breast cancer were more likely to have manifested an increased A and E excretion. The reversal in the relationship between androgen metabolite excretion and risk suggests that age, or probably more importantly, menopausal status at diagnosis is an important modifying factor. Dichotomizing at age 50 it was found that in the younger age group (predominantly premenopausal) the rate ratios in the lowest tertile of A or E excretion were two- to threefold greater than for those in the highest tertile (χ2 1= 3.57; P = 0.06: χ2 1= 4.70; P = 0.03 for A and E respectively). In contrast, in the older age group comprising predominantly post-menopausal women, the rate ratios associated with the lowest tertile of A or E were half that of those in the highest tertile (χ2 1= 4.10; P = 0.04; χ2 1= 8.72; P = 0.003 for A and E respectively). This suggests that there may be different endocrine promotional factors for pre-and post-menopausal breast cancer. Hormonal risk factors may vary during the lifetime of an individual woman and this may have profound consequences for prevention strategies. © 2000 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Aalen O (1978) Non-parametric inference for a family of counting processes. Ann Stat 6: 701–726
Adami HO, Johansson ED, Vegelius J and Victor A (1979) Serum concentration of estrone, androstenedione, testosterone and sex-hormone-binding globulin in postmenopausal women with breast cancer in age-matched controls. Upsala J Med Sci 84: 259–274
Adams JB (1983) Hermaphrodiol: a ‘new’ estrogen and its role in the etiology of human breast cancer. In: Commentaries on Research in Breast Diseases, Bulbrook RD, Taylor DJ (eds), pp. 131–161, Alan R. Liss: New York
Adams JB (1998) Adrenal androgens and human breast cancer: a new appraisal. Breast Cancer Res Treat 51: 183–188
Bonney RC, Scanlon MJ, Reed MJ, Jones DL, Beranek PA and James VHT (1984) Adrenal androgen concentrations in breast tumours and in normal breast tissue. The relationship to oestradiol metabolism. J Steroid Biochem 20: 501–504
Bulbrook RD and Hayward JL (1967) Abnormal urinary steroid excretion and subsequent breast cancer. A prospective study in the Island of Guernsey. Lancet i: 519–522
Bulbrook RD, Hayward JL and Spicer CC (1971) Relation between urinary androgen and corticoid excretion and subsequent breast cancer. Lancet ii: 395–398
Clayton B and Mills M (1993) Statistical Models in Epidemiology, Oxford University Press: Oxford
De Waard F (1969) The epidemiology of breast cancer: review and prospects. Int J Cancer 40: 577–586
De Waard F, deLaive JWJ and Baanders van Halewjin EA (1960) On bimodal age distribution of mammary carcinoma. Br J Cancer 14: 437–448
De Waard F, Baanders van Halewjin EA and Huizinga J (1964) The bimodal age distribution of patients with mammary carcinoma. Cancer 17: 141–151
Dorgan JF, Longcope C, Stephenson HE, Falk RT, Miller R and Sciajno R (1996) Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol Biomarkers Prevent 5: 533–539
Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L and Wolmark N (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 90: 13712–13788
Grattarola R, Secreto G, Recchione C and Castellini W (1974) Androgens in breast cancer II. Endometrial adenocarcinoma and breast cancer in married postmenopausal women. Am J Obstet 118: 173–178
Hayward JL, Greenwood FC, Glober G, Stemmerman G, Bulbrook RD, Wang DY and Kumaoka S (1978) Endocrine status in normal British, Japanese and Hawaiian-Japanese women. Eur J Cancer 14: 1221–1228
Hill P, Garbaczewski L and Kasumi F (1985) Plasma testosterone and breast cancer. Eur J Cancer Clin Oncol 21: 1265–1266
Hsieh C-C, Trichopoulos D, Katsouyanni K and Yuasa S (1990) Age at menarche, age at menopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case–control study. Int J Cancer 46: 796–800
Huggins C, Jensen CV and Cleveland AS (1954) Chemical structure of steroids in relation to promotion of growth of the vagina and uterus of the hypophysectomized rat. J Exp Med 100: 225–240
Kellie AE and Wade AP (1957) The analysis of urinary 17-oxosteroids by gradient elution. Biochem J 66: 196–206
Key TJA and Pike MC (1988) The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 24: 29–43
Key TJA, Wang DY, Brown JB, Allen DS, Moore JW, Bulbrook RD, Fentiman IS and Pike MC (1996) A prospective study of oestrogen excretion and breast cancer risk. Br J Cancer 73: 1615–1619
Lynch HT and Lynch JF (1986) Breast cancer genetics in an oncology clinic: 328 consecutive patients. Cancer Genet Cytogenet 23: 369–372
Manton KG and Stallard E (1980) A two-disease model of female breast cancer: mortality in 1969 among white females in the United States. J Natl Cancer Inst 64: 9–16
McFadyen IJ, Forrest AP, Prescott RJ, Golder MP, Groom GV, Fahmy DR and Griffiths K (1976) Circulating hormone concentrations in women with breast cancer. Lancet i: 1100–1102
Powles T, Eeles R, Ashley S, Easton D, Chang J, Dowsett M, Tidy A, Viggers J and Davey J (1998) Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 352: 98–101
Reed MJ (1995) The discriminant-function test: a marker of Th1/Th2 cell cytokine secretion and breast tumour oestrogen synthesis. Mol Med Today 1: 98–103
Salber EJ, Trichopoulos D and MacMahon B (1969) Lactation and reproductive histories of breast cancer patients in Boston, 1965–66. J Natl Cancer Inst 43: 1013–1024
Secreto G and Zumoff B (1994) Abnormal production of androgens in women with breast cancer. Anticancer Res 14: 2113–2118
Secreto G, Recchione C, Cavalleri A, Miraglia M and Dati V (1993) Circulating levels of testosterone, 17-beta-oestradiol, luteinising hormone and prolactin in postmenopausal breast cancer patients. Br J Cancer 47: 269–275
Secreto G, Toniolo P, Berrino F, Recchione C, Cavalleri A, Pisani P, Totis A, Fariselli G and Di Pietro S (1991) Serum and urinary androgens and risk of breast cancer in postmenopausal women. Cancer Res 51: 2572–2576
Seymour-Munn K and Adams JB (1983) Estrogenic effects of 5-androsterone-3β-17β-diol and its possible implication in the etiology of breast cancer. Endocrinology 112: 486–491
Thomas BS and Bulbrook RD (1966) Routine assay of urinary dehydroepiandrosterone, androsterone, and aetiocholanolone in urine by gas-liquid chromatography. In: Vermeulen A (ed.), Androgens in Normal and Pathological Conditions, pp. 49–53, Excerpta Medica Foundation: Amsterdam
Thomas BS and Walton DRM (1968) Chloromethyldimethylsilyl ethers in the routine assay of urinary 11-deoxy-17-oxosteroids by gas-liquid chromatography. J Endocr 41: 203–211
Thomas HV, Key TJ, Allen DS, Moore JW, Dowsett M, Fentiman IS and Wang DY (1997a) 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
Thomas HV, Key TJ, Allen DS, Moore JW, Dowsett M, Fentiman IS and Wang DY (1997b) A prospective study of endogenous serum hormone concentrations and breast cancer risk in postmenopausal women on the island of Guernsey. Br J Cancer 76: 401–405
Thomas HV, Reeves GK and Key TJ (1997c) Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 8: 922–928
Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, Banerjee S, Koenig KL, Shore RE, Strax P and Pasternack BS (1995) A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Cancer Inst 87: 190–197
van Doorn LG, Poortman J, Thijssen JHH and Schwarz F (1981) Action and interactions of 5-androstene-3β,17β-diol and estradiol-17β in the immature rat uterus. Endocrinology 108: 1587–1593
Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C, Rotmensz N and Boyle P (1998) Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Lancet 352: 93–97
Wang DY, Moore JW, Thomas BS, Bulbrook RD, Hayward JL, Abe O, Utsunomiye J, Kumaoka S, Greenwood FC, Glober G and Stemmerman G (1979) Plasma and urinary androgens in women with varying degrees of risk of breast cancer. Eur J Cancer 15: 1269–1274
Wang DY, De Stavola BL, Bulbrook RD, Allen DS, Kwa HG, Fentiman IS, Hayward JL and Millis RR (1992) Relationship of blood prolactin levels and the risk of subsequent breast cancer. Int J Epidemiol 21: 214–221
Wang DY, De Stavola BL, Allen DS, Fentiman IS, Hayward JL and Bulbrook RD (1997) Breast cancer risk is positively associated with height. Breast Cancer Res Treat 43: 123–128
Zeleniuch-Jacquotte A, Bruning PF, Bonfrer JMG, Koenig KL, Shore RE and Kim MY (1997) Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to risk of breast cancer in postmenopausal women. Am J Epidemiol 145: 1030–1038
Zhang Y, Kiel DP, Kreger BF, Cupples LA, Ellison RC, Dorgan JF, Schatzkin A, Levy D and Felson DT (1997) Bone mass and the risk of breast cancer among postmenopausal women. N Engl J Med 336: 611–617
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Wang, D., Allen, D., Stavola, B. et al. Urinary androgens and breast cancer risk: results from a long-term prospective study based in Guernsey. Br J Cancer 82, 1577–1584 (2000). https://doi.org/10.1054/bjoc.1999.1180
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.1999.1180
Keywords
This article is cited by
-
γ-Glutamyl transferase and breast cancer risk
British Journal of Cancer (2010)
-
Lifetime cumulative number of menstrual cycles and serum sex hormone levels in postmenopausal women
Breast Cancer Research and Treatment (2008)
-
Endocrine management of breast cancer—biology and current practice
European Clinics in Obstetrics and Gynaecology (2005)