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Relation of serum levels of estrogen and dehydroepiandrosterone sulfate to hormone receptor status among postmenopausal women with breast cancer

Breast Cancer volume 14, pages 269–276 (2007)Cite this article

Abstract

Background: It is hypothesized that breast cancer may consist of heterogeneous diseases with different hormonal environments classified by hormone receptor status. Epidemiologic studies evaluating risk factors for breast cancer by hormone receptor status have supported the hypothesis. However, there are inconsistencies in the risk factor profiles by estrogen receptor (ER) and progesterone receptor (PR) across the studies. To clarify the heterogeneity of the disease, it is necessary to understand not only risk factor profiles but also the biologic characteristics such as the relationships among endogenous sex hormone levels and hormone receptors.

Methods: We measured serum levels of estrone (E1), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) in 142 postmenopausal women aged 50 and over with primary breast cancer who had undergone surgical treatment, and investigated the heterogeneity in the relations of endogenous sex hormone levels to hormone receptor status, using the case-series study method. Subjects were categorized into 3 classes based on tertiles of each hormone level in receptor-negative subjects, and odds ratios (ORs) for receptor-positive status compared with receptor-negative status were computed, taking the lowest category as a reference category.

Results: There were clear trends toward higher serum levels of E1, E2, and DHEAS in women with PR+ cancer. The case-series approach revealed that PR+ status might be strongly associated with serum sex hormone levels. In particular, the OR of PR+ was large for a high DHEAS level (OR for the highest category = 4.28). No significant association between serum hormone levels and ER status was observed.

Conclusion: The association of serum sex hormone levels with hormone receptor status may differ by PR status, but not by ER status. This finding suggests that PR status may be related to the heterogeneity in hormonal environments associated with breast cancer risk.

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Abbreviations

ER:

Estrogen receptor

PR:

Progesterone receptor

E1:

Estrone

E2:

Estradiol

DHEAS:

Dehydroepiandrosterone sulfate

SHBG:

Sex hormone-binding globulin

OR:

Odds ratio

CI:

Confidence interval

References

  1. Bernstein L, Ross RK: Endogenous hormones and breast cancer risk.Epidemiol Rev 15:48–65, 1993.

    PubMed  CAS  Google Scholar 

  2. Rayter Z: Steroid receptors in breast cancer.Br J Surg 78:528–535,1991.

    PubMed  Article  CAS  Google Scholar 

  3. Habel LA, Stanford JL: Hormone receptors and breast cancer.Epidemiol Rev 15:209–219, 1993.

    PubMed  CAS  Google Scholar 

  4. Nomura Y, Miura S, Koyama H, Enomoto K, Kasumi F, Yamamoto H, Kimura M, Tominaga T, Iino H, Morimoto T, Tashiro H: Relative effects of steroid hormone receptors on the prognosis of patients with operable breast cancer.Cancer 69:153–164, 1992.

    PubMed  Article  CAS  Google Scholar 

  5. Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thürlimann B, Senn H-J: Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer.J Clin Oncol 65:3357–3365, 2003.

    Article  Google Scholar 

  6. Hildreth NG, Kelsey JL, Eisenfeld AJ, LiVolsi VA, Holford TR, Fischer DB: Differences in breast cancer risk factors according to the estrogen receptor level of the tumor.J Natl Cancer Inst 70:1027–1031,1983.

    PubMed  CAS  Google Scholar 

  7. Hislop TG, Coldman AJ, Elwood JM, Skippen DH, Kan L: Relationship between risk factors for breast cancer and hormonal status.Int J Epidemiol 15:469–476, 1986.

    PubMed  Article  CAS  Google Scholar 

  8. Kreiger N, King WD, Rosenberg L, Clarke EA, Palmer JR, Shapiro S: Steroid receptor status and epidemiology of breast cancer.Ann Epidemiol 1:513–523, 1991.

    PubMed  CAS  Google Scholar 

  9. Potter JD, Cerhan JR, Sellers TA, McGovern PG, Drinkard C, Kushi LR, Folsom AR: Progesterone and estrogen receptors and mammary neoplasia in the Iowa Women’s Health Study: how many kinds of breast cancer are there?Cancer Epidemiol Biomarkers Prev 4:319–326, 1995.

    PubMed  CAS  Google Scholar 

  10. Yoo K-Y, Tajima K, Miura S, Takeuhi T, Hirose K, Risch H, Dubrow R: Breast cancer risk factors according to combined estrogen and progesterone receptor status: a case-control analysis.Am J Epidemiol 146:307–314, 1997.

    PubMed  CAS  Google Scholar 

  11. Huang W-Y, Newman B, Millikan RC, Schell MJ, Hulka BS, Moorman PG: Hormone-related factors and risk of breast cancer in relation to estrogen receptor and progesterone receptor status.Am J Epidemiol 151:703–714, 2000.

    PubMed  CAS  Google Scholar 

  12. Yoo K-Y, Tajima K, Park S-K, Kang D, Kim S-U, Hirose K, Takeuchi T, Miura S: Postmenopausal obesity as a breast cancer risk factor according to estrogen and progesterone receptor status (Japan).Cancer Lett 167:57–63, 2001.

    PubMed  Article  CAS  Google Scholar 

  13. Colditz GA, Rosner BA, Chen WY, Holmes MD, Hankinson SE: Risk factors for breast cancer according to estrogen and progesterone receptor status.J Natl Cancer Inst 96:218–228, 2004.

    PubMed  CAS  Google Scholar 

  14. Begg CB, Zhang ZF: Statistical analysis of molecular epidemiology studies employing case-series.Cancer Epidemiol Biomarkers Prev 3:173–175, 1994.

    PubMed  CAS  Google Scholar 

  15. Minami Y, Ohuchi N, Fukao A, Hisamichi S: Risk factors for breast cancer: a case-control study of screen- detected breast cancer in Miyagi Prefecture, Japan.Breast Cancer Res Treat 44:225–233, 1997.

    PubMed  Article  CAS  Google Scholar 

  16. Swede H, Moysich KB, Freudenheim JL, Quirk JT, Muti PC, Hurd TC, Edge SB, Winston JS, Michalek AM: Breast cancer risk factors and HER2 over-expression in tumors.Cancer Detect Prev 25:511–519, 2001.

    PubMed  CAS  Google Scholar 

  17. Tavassoli FA: Pathology of The Breast, 2nd ed, McGraw-Hill, New York, pp52–53, 1992.

    Google Scholar 

  18. Fletcher RH, Fletcher SW, Wagner EH: Clinical Epidemiology: the essentials, 2nd ed, Williams & Wilkins, Baltimore, pp42–75, 1988.

    Google Scholar 

  19. Minami Y, Tateno H: Associations between cigarette smoking and the risk of four leading cancers in Miyagi Prefecture, Japan: a multi-site case-control study.Cancer Sci 94:540–547, 2003.

    PubMed  Article  CAS  Google Scholar 

  20. Breslow NE, Day NE: Statistical methods in cancer research, vol. 1. The analysis of case-control studies, International Agency for Research on Cancer, Lyon, ppl92-246, 1980.

  21. SAS/STAT User’s Guide, release 6.03 ed, SAS Institute Inc., Cary, 1988.

  22. Thomas HV, Reeves GK, Key TJA: Endogenous estrogen and postmenopausal breast cancer: a quantitative review.Cancer Causes Control 8:922–928, 1997.

    PubMed  Article  CAS  Google Scholar 

  23. Kabuto M, Akiba S, Stevens RG, Neriishi K, Land CE: A prospective study of estradiol and breast cancer in Japanese women.Cancer Epidemiol Biomarkers Prev 9:575–579, 2000.

    PubMed  CAS  Google Scholar 

  24. 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 94:606–616, 2002.

    Google Scholar 

  25. Zeleniuch-Jacquotte A, Toniolo P, Levitz M, Shore RE, Koenig KL, Banerjee S, Strax P, Pasternack BS: Endogenous estrogens and risk of breast cancer by estrogen receptor status: a prospective study in postmenopausal women.Cancer Epidemiol Biomarker Prev 4:857–860, 1995.

    CAS  Google Scholar 

  26. Miyoshi Y, Tanji Y, Taguchi T, Tamaki Y, Noguchi S: Associations of serum estrone levels with estrogen receptor-positive breast cancer risk in postmenopausal Japanese women.Clin Cancer Res 9:2229–2233, 2003.

    PubMed  CAS  Google Scholar 

  27. Missmer SA, Eliassen H, Barbieri RL, Hankinson SE: Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women.J Natl Cancer Inst 96:1856–1865, 2004.

    PubMed  CAS  Article  Google Scholar 

  28. Cummings SR, Lee JS, Lui L-Y, Stone K, Ljung BM, Cauleys JA: Sex hormones, risk factors, and risk of estrogen receptor-positive breast cancer in older women: a long-term prospective study.Cancer Epidemiol Biomarker Prev 14:1047–1051, 2005.

    Article  CAS  Google Scholar 

  29. Marshall RJ, Chisholm EM: Hypothesis testing in the polychotomous logistic model with an application to detecting gastrointestinal cancer.Stat Med 4:337–344, 1985.

    PubMed  Article  CAS  Google Scholar 

  30. Dubin N, Pasternack BS: Risk assessment for case- control subgroups by polychotomous logistic regression.Am J Epidemiol 123:1101–1117,1986.

    PubMed  CAS  Google Scholar 

  31. 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, Wolmark N: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.J Natl Cancer Inst 90:1371–1388, 1998.

    PubMed  Article  CAS  Google Scholar 

  32. Cummings SR, Duong T, Kenyon E, Cauley JA, Whitehead M, Krueger KA: Serum estradiol level and risk of breast cancer during treatment with raloxifene.JAMA 287:216–220, 2002.

    PubMed  Article  CAS  Google Scholar 

  33. Judd HL, Shamonki IM, Frumar AM, Lagasse LD: Origin of serum estradiol in postmenopausal women.Obstet Gynecol 59:680–686, 1982.

    PubMed  CAS  Google Scholar 

  34. Siiteri PK: Adipose tissue as a source of hormones.Am J Clin Nutr 45:277–282, 1987.

    PubMed  CAS  Google Scholar 

  35. Thijssen JHH, van Landeghem AAJ, Poortman J: Uptake and concentration of steroid hormones in mammary tissues.Ann N Y Acad Sci 464:106–116, 1986.

    PubMed  Article  CAS  Google Scholar 

  36. Larionov AA, Berstein LM, Miller WR: Local uptake and synthesis of oestrone in normal and malignant postmenopausal breast tissues.J Steroid Biochem Mol Biol 81:57–64, 2002.

    PubMed  Article  CAS  Google Scholar 

  37. Nakata T, Takashima S, Shiotsu Y, Murakata C, Ishida H, Akinaga S, Li P-K, Sasano H, Suzuki T, Saeki T: Role of steroid sulfatase in local formation of estrogen in postmenopausal breast cancer patients.J Steroid Biochem Mol Biol 86:455–460, 2003.

    PubMed  Article  CAS  Google Scholar 

  38. Lapidus RG, Nass SJ, Davidson NE: The loss of estrogen and progesterone receptor gene expression in human breast cancer.J Mammary Gland Biol Neoplasia 3:85–94, 1998.

    PubMed  Article  CAS  Google Scholar 

  39. McGuire WL, Horwitz KB: A role for progesterone in breast cancer.Ann N Y Acad Sci 286:90–100,1977.

    PubMed  Article  CAS  Google Scholar 

  40. Savouret JF, Perrot-Applanet M, Lescop P, Guiochon-Mantel A, Chauchereau A, Milgrom, E: Mechanisms controlling the cellular traffic and the concentration of the progesterone receptor.Ann N Y Acad Sci 684:11–18, 1993.

    PubMed  Article  CAS  Google Scholar 

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Author information

Affiliations

  1. Division of Surgery, Miyagi Cancer Center Hospital, 2-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan

    Yoichiro Kakugawa, Hiroko Inoue & Tsuneaki Fujiya

  2. Division of Community Health, Tohoku University School of Health Sciences, 2-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan

    Yuko Minami

  3. Division of Epidemiology, Miyagi Cancer Center Research Institute, 2-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan

    Yuko Minami

  4. Division of Pathology, Miyagi Cancer Center Research Institute, 2-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan

    Hiroo Tateno

Authors
  1. Yoichiro Kakugawa
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  2. Yuko Minami
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  3. Hiroo Tateno
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  4. Hiroko Inoue
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  5. Tsuneaki Fujiya
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Corresponding author

Correspondence to Yuko Minami.

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Kakugawa, Y., Minami, Y., Tateno, H. et al. Relation of serum levels of estrogen and dehydroepiandrosterone sulfate to hormone receptor status among postmenopausal women with breast cancer. Breast Cancer 14, 269–276 (2007). https://doi.org/10.2325/jbcs.14.269

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  • DOI: https://doi.org/10.2325/jbcs.14.269

Key words

  • Breast cancer
  • Dehydroepiandrosterone sulfate
  • Estrogen
  • Estrogen receptor
  • Progesterone receptor