Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Dehydroepiandrosterone concentration in breast cancer tissue is related to its plasma gradient across the mammary gland

  • 17 Accesses

  • 11 Citations


Dehydroepiandrosterone (DHEA) has been shown to affect the growth of mammary carcinomas bothin vitro andin vivo. In humans, very high levels of DHEA and/or dehydroepiandrosterone sulfate (DHEAS) have been found in breast tissues and secretions, and epidemiological studies suggest a role of these steroids in the modulation of breast cancer growth. An uptake from plasma and a transformation from precursors can be both postulated, but the main source of the adrenal C19 steroids found within the breast is debated.

Attempting to clarify this point, in ten patients undergoing surgery for breast cancer we studied: a) DHEAS and DHEA concentrations in tumor tissue; b) the differences between DHEAS (or DHEA) concentration in peripheral venous plasma and that draining the affected breast, that we assume to reflect the arteriovenous gradient of these steroids; c) DHEA sulfatase activity in tumor tissue.

Results show that DHEA sulfatase activity is not related to DHEAS or DHEA concentrations in breast cancer tissue. A negative DHEA plasma gradient across the breast is unveiled, whereas DHEAS levels are not different in blood supplying and draining the breast with cancer. The DHEA plasma gradient across the breast is positively related to DHEA concentration in tumor tissue.

Data are consistent with the hypothesis that the plasma source contributes remarkably to DHEA found within breast cancer tissue.

This is a preview of subscription content, log in to check access.


  1. 1.

    Najid A, Habrioux G: Biological effects of adrenal androgens on MCF-7 and BT-20 human breast cancer cells. Oncology 47: 269–274, 1990

  2. 2.

    Boccuzzi G, Brignardello E, Di Monaco M, Forte C, Leonardi L, Pizzini A: Influence of dehydroepiandrosterone and 5-en-androstene-3β,17β-diol on the growth of MCF-7 human breast cancer cells induced by 17β-estradiol. Anticancer Res 12: 799–804, 1992

  3. 3.

    Boccuzzi G, Aragno M, Brignardello E, Tamagno E, Conti G, Di Monaco M, Racca S, Danni O, Di Carlo F: Opposite effects of dehydroepiandrosterone on the growth of 7,12-dimethylbenz(a)-anthracene-induced rat mammary carcinomas. Anticancer Res 12: 1479–1484, 1992

  4. 4.

    Spinola PG, Marchetti B, Labrie F: Adrenal steroids stimulate growth and progesterone receptor levels in rat uterus and DMBA-induced mammary tumors. Breast Cancer Res Treat 8: 241–248, 1986

  5. 5.

    Secreto G, Toniolo P, Berrino F, Recchione C, Cavalleri A, Pisani P, Totis A, Fariselli G, Di Pietro S: Serum and urinary androgens and risk of breast cancer in postmenopausal women. Cancer Res 51: 2572–2576, 1991

  6. 6.

    Gordon GB, Bush TL, Helzlsouer KJ, Miller SR, Comstock GW: Relationship of serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulphate to the risk of developing post-menopausal breast cancer. Cancer Res 50: 3859–3862, 1990

  7. 7.

    Van Landeghem AAJ, Poortman J, Nabuurs M, Thijssen JHH: Endogenous concentrations and subcellular distribution of androgens in normal and malignant human breast tissue. Cancer Res 45: 2907–2912, 1985

  8. 8.

    Miller WR, Humeniuk V, Kelly RW: Dehydroepiandrosterone sulphate in breast secretions. J Steroid Biochem 137: 145–151, 1980

  9. 9.

    Boccuzzi G, Brignardello E, Massobrio M, Bonino L: Breast duct fluid dehydroepiandrosterone sulphate in fibrocystic disease. Eur J Cancer Clin Oncol 23: 1099–1102, 1987

  10. 10.

    Bradlow HL, Fukushima DK, Rosenfeld RS, Boyer RM, Kream J, Fleisher M, Schwartz MK: Hormone levels in breast cyst fluid. Clin Chem 22: 1213, 1976

  11. 11.

    Boccuzzi G, Brignardello E, Daniele D, Giorda C, Agrimonti F: Concentrations intrakystiques des androgenes surrenaliens dans la maladie fibro-kystique du sein. Senologia 6: 193–198, 1981

  12. 12.

    Vermeulen A, Deslypere JP: Biosynthesis of active oestrogens in the breast. Proc R Society of Edinburgh 95B: 195–201, 1989

  13. 13.

    Van Landeghem AAJ, Poortman J, Deshpande N, Di Martino L, Tarquini A, Thijssen JHH, Schwarz F: Plasma concentration gradient of steroid hormones across human mammary tumorsin vivo. J Steroid Biochem 14: 741–747, 1981

  14. 14.

    Adams JB: Steroid hormones and human breast carcinoma: an hypothesis. Cancer 40: 325–333, 1977

  15. 15.

    Adams JB, Archibald L, Clarke C: Adrenal dehydroepiandrosterone and human mammary cancer. Cancer Res 38: 4036–4040, 1978

  16. 16.

    Prost O, Turrel MO, Dahan N, Craveur C, Adessi GL: Estrone and dehydroepiandrosterone sulphatase activities and plasma estrone sulphate levels in human breast carcinoma. Cancer Res 44: 661–664, 1984

  17. 17.

    Schacterle GR, Pollock RL: A simplified method for the quantitative assay of small amounts of protein in biological material. Analyt Biochem 51: 654–655, 1973

  18. 18.

    Burstein S, Dorfman RI: Determination of mammalian steroid sulfatase with [7-3H]β-hydroxy-androst-5-en-17-one sulfate. J Biol Chem 238: 1656–1660, 1963

  19. 19.

    Migliardi M, Cenderelli G, Cassoni P, Menzaghi C, Spinnato MR, Camanni M, De Filippis V, Massobrio M, Zoppetti G: Adrenal androgens dynamics in breast cancer (Abstract). J Steroid Biochem 33: 24, 1989

  20. 20.

    Shao TC, Castaneda E, Rosenfield RL, Liao S: Selective retention and formation of Δ5-androstenediol-receptor complex in cell nuclei of the rat vagina. J Biol Chem 250: 3095–3100, 1975

  21. 21.

    Adams JB: Enzymic synthesis of steroid sulphates. II. Presence of steroid sulphokinase in human mammary carcinoma extracts. J Clin Endocrinol Metab 24: 988–996, 1964

  22. 22.

    Vermeulen A, Deslypere JP, Paridaens R, Leclercq G, Roy F, Heuson JC: Aromatase, 17β-hydroxysteroid dehydrogenase, and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women. Eur J Cancer Clin Oncol 22: 515–525, 1986

  23. 23.

    Brignardello E, Pizzini A, Caliendo V, Magliona G, Massobrio M, Boccuzzi G: Breast tissue and breast duct fluid DHAS concentrations in premenopausal mammary cancer and fibrocystic disease. Ann NY Acad Sci 595: 467–472, 1990

  24. 24.

    Bradlow HL, Schwartz MK, Fleisher M, Rosenfeld RS, Kream J, Schwartz D, Breed CN, Fracchia AA: Hormone levels in human breast cyst fluid. In: Angeli A, Bradlow HL, Dogliotti L (eds) Endocrinology of Cystic Breast Disease, Raven Press, New York, 1983, pp 59–75

  25. 25.

    Gower DB, Cooke GM: Regulation of steroid-transforming enzymes by endogenous steroids. J Steroid Biochem 19: 1527–1556, 1983

  26. 26.

    Adams JB: Human breast cancer: concerted role of diet, prolactin and adrenal C195-steroids in tumorigenesis. Int J Cancer 50: 854–858, 1992

Download references

Author information

Correspondence to Enrico Brignardello.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Brignardello, E., Cassoni, P., Migliardi, M. et al. Dehydroepiandrosterone concentration in breast cancer tissue is related to its plasma gradient across the mammary gland. Breast Cancer Res Tr 33, 171–177 (1995). https://doi.org/10.1007/BF00682724

Download citation

Key words

  • breast cancer
  • dehydroepiandrosterone
  • DHEA-sulfatase