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Endogenous estrogen and postmenopausal breast cancer: a quantitative review

Abstract

This paper systematically reviews the results from epidemiologic studies investigating the hypothesis that breast cancer risk inpostmenopausal women increases with increasing concentrations of estradiol in blood and with increasing urinary estrogen excretion rates. Data from 29epidemiologic studies of endogenous hormones and postmenopausal breast cancer were used. The ratio of the average estrogen concentration in the women with breast cancer to that in the women without breast cancer (and its 95 percent confidence interval [CI]) was calculated for each study, and the results were summarized by calculating weighted averages of the log ratios. In six prospective studies of serum estradiol concentration, 329 women who subsequently developed breast cancer had, overall, a 15 percent (CI = 6-24percent, P = 0.0003) higher mean concentration of estradiol in their blood than the 1,105 women who remained free of cancer. The results of these prospective studies did not differ significantly from each other(chi-squared for heterogeneity = 8.7; degrees of freedom = 5; P > 0.1).Similar differences in mean estrogen levels were seen in the case-control studies which reported either estradiol concentrations in the blood or urinary estrogen excretion. However, the case-control studies showed significant heterogeneity among their results. The data from the prospective studies strongly suggest that breast cancer risk in postmenopausal women is associated with relatively high concentrations of endogenous estradiol.

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References

  1. 1.

    Pike MC, Spicer DV, Dahmoush L, Press MF. Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 1993; 15: 17–35.

    PubMed  CAS  Google Scholar 

  2. 2.

    Key TJ, Pike MC. The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 1988; 24: 29–43.

    PubMed  CAS  Article  Google Scholar 

  3. 3.

    Forrest APM. Concluding remarks. Proc Royal Soc Edinburgh 1989; 95B: 305–7.

    Google Scholar 

  4. 4.

    Bernstein L, Ross RK, Pike MC, Brown JB, Henderson BE. Hormone levels in older women: a study of post-menopausal breast cancer patients and healthy population controls. Br J Cancer 1990; 61: 298–302.

    PubMed  CAS  Google Scholar 

  5. 5.

    Lemon HM, Wotiz HH, Parsons L, Mozden PJ. Reduced estriol excretion in patients with breast cancer prior to endocrine therapy. JAMA 1966; 196: 1128–36.

    Article  Google Scholar 

  6. 6.

    Krishnamoorthy G, Govindarajulu P, Ramalingam V. Serum hormones in human breast cancer subjects. Neoplasma 1989; 36: 221–31.

    PubMed  CAS  Google Scholar 

  7. 7.

    Ota DM, Jones LA, Jackson GL, Jackson PM, Kemp K, Bauman D. Obesity, non-protein-bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients. Cancer 1986; 57: 558–62.

    PubMed  CAS  Article  Google Scholar 

  8. 8.

    McFadyen IJ, Forrest AP, Prescott RJ, et al. Circulating hormone concentrations in women with breast cancer. Lancet 1976; i: 1100–2.

    Article  Google Scholar 

  9. 9.

    Argüelles AE, Poggi UL, Saborida C, Hoffman C, Chekherdemian M, Blanchard O. Endocrine profiles and breast cancer. Lancet 1973; i: 165–8.

    Article  Google Scholar 

  10. 10.

    Marmorston J, Crowley LG, Myers SM, Stern E, Hopkins CE. II. Urinary excretion of estrone, estradiol, and estriol by patients with breast cancer and benign breast disease. Am J Obst & Gynec 1965; 92: 460–7.

    CAS  Google Scholar 

  11. 11.

    Grönroos M, Aho AJ. Estrogen metabolism in postmenopausal women with primary and recurrent breast cancer. Eur J Cancer 1968; 4: 523–7.

    PubMed  Google Scholar 

  12. 12.

    England PC, Skinner LG, Cottrell KM, Sellwood RA. Serum oestradiol-17 beta in women with benign and malignant breast disease. Br J Cancer 1974; 30: 571–6.

    PubMed  CAS  Google Scholar 

  13. 13.

    Morreal CE, Dao TL, Nemoto T, Lonergan PA. Urinary excretion of estrone, estradiol, and estriol in postmenopausal women with primary breast cancer. JNCI 1979; 63: 1171–4.

    PubMed  CAS  Google Scholar 

  14. 14.

    Reed MJ, Cheng RW, Noel CT, Dudley HA, James VH. Plasma levels of estrone, estrone sulfate, and estradiol and the percentage of unbound estradiol in postmenopausal women with and without breast disease. Cancer Res 1983; 43: 3940–3.

    PubMed  CAS  Google Scholar 

  15. 15.

    Bruning PF, Bonfrer JM, Hart AA. Non-protein bound oestradiol, sex hormone binding globulin, breast cancer and breast cancer risk. Br J Cancer 1985; 51: 479–84.

    PubMed  CAS  Google Scholar 

  16. 16.

    El-Aaser AA, El-Merzabani MM, Abu-Bedair FA. Serum estrogen level in Egyptian breast cancer patients. Tumori 1985; 71: 293–5.

    PubMed  CAS  Google Scholar 

  17. 17.

    Siiteri PK, Simberg N, Murai J. Estrogens and breast cancer. Ann N Y Acad Sci 1986; 464: 100–5.

    PubMed  CAS  Google Scholar 

  18. 18.

    The Anglo-Egyptian Health Agreement Collaborative Study. Serum hormone levels in breast cancer patients and controls in Egypt and Great Britain. The Anglo-Egyptian Health Agreement Collaborative Study. Eur J Cancer Clin Oncol 1988; 24: 1329–35.

    Article  Google Scholar 

  19. 19.

    Bennett IC, McCaffrey JF, McCaffrey E, Wyatt B. Serum oestradiol in women with and without breast disease [published erratum appears in Br J Cancer1990; 6: 336]. Br J Cancer1990; 61: 142–6.

    PubMed  CAS  Google Scholar 

  20. 20.

    Blankenstein MA, Szymczak J, Daroszewski J, Milewicz A, Thijssen JH. Estrogens in plasma and fatty tissue from breast cancer patients and women undergoing surgery for non-oncological reasons.Gynecol Endocrinol 1992; 6: 13–7.

    PubMed  CAS  Google Scholar 

  21. 21.

    Persson BH, Risholm L. Oophorectomy and cortisone treatment as a method of eliminating oestrogen production in patients with breast cancer. Acta Endocrinologica 1964; 47: 15–26.

    CAS  Google Scholar 

  22. 22.

    Pearce S, Dowsett M, McKinna JA. Albumin-bound and non-protein-bound oestradiol and testosterone in postmenopausal breast disease.Eur J Cancer 1991; 27: 259–63.

    PubMed  CAS  Article  Google Scholar 

  23. 23.

    Wysowski DK, Comstock GW, Helsing KJ, Lau HL. Sex hormone levels in serum in relation to the development of breast cancer. Am J Epidemiol 1987; 125: 791–9.

    PubMed  CAS  Google Scholar 

  24. 24.

    Garland CF, Friedlander NJ, Barrett-Connor E, Khaw KT. Sex hormones and postmenopausal breast cancer: a prospective study in an adult community. Am J Epidemiol 1992; 135: 1220–30.

    PubMed  CAS  Google Scholar 

  25. 25.

    Helzlsouer KJ, Alberg AJ, Bush TL, Longcope C, Gordon GB, Comstock GW. A prospective study of endogenous hormones and breast cancer. Cancer Detect Prev 1994; 18: 79–85.

    PubMed  CAS  Google Scholar 

  26. 26.

    Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, et al. A prospective study of endogenous estrogens and breast cancer in postmenopausal women.JNCI 1995; 87: 190–7.

    PubMed  CAS  Google Scholar 

  27. 27.

    Berrino F, Muti P, Micheli A, et al. Serum sex hormone levels after menopause and subsequent breast cancer. JNCI 1996; 88: 291–6.

    PubMed  CAS  Google Scholar 

  28. 28.

    Dorgan JF, Longcope C, Stephenson HE, et al. Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol Biomark Prev 1996; 5: 533–9.

    CAS  Google Scholar 

  29. 29.

    Thomas HV, Key TJ, Allen DS, et al. A prospective study of endogenous serum hormone concentrations and breast cancer risk in postmenopausal women on the island of Guernsey. Br J Cancer 1997; 76: 401–5.

    PubMed  CAS  Google Scholar 

  30. 30.

    Moore JW, Clark GM, Bulbrook RD, et al. Serum concentrations of total and non-protein-bound oestradiol in patients with breast cancer and in normal controls. Int J Cancer 1982; 29: 17–21.

    PubMed  CAS  Google Scholar 

  31. 31.

    Jones LA, Ota DM, Jackson GA, et al. Bioavailability of estradiol as a marker for breast cancer risk assessment. Cancer Res 1987; 47: 5224–9.

    PubMed  CAS  Google Scholar 

  32. 32.

    Zaridze D, Kushlinskii N, Moore JW, Lifanova YE, Bassalyk L, Wang DY. Endogenous plasma sex hormones in pre-and postmenopausal women with breast cancer: results from a case-control study in Moscow. Eur J Cancer Prev 1992; 1: 225–30.

    PubMed  CAS  Google Scholar 

  33. 33.

    Grattarola R, Secreto G, Recchione C, Castellini W. Androgens in breast cancer. II. Endometrial adenocarcinoma and breast cancer in married postmenopausal women. Am J Obstet Gynecol 1974; 118: 173–8.

    PubMed  CAS  Google Scholar 

  34. 34.

    Key TJA, Wang DY, Brown JB, et al. A prospective study of urinary oestrogen excretion and breast cancer risk. Br J Cancer 1996; 73: 1615–9.

    PubMed  CAS  Google Scholar 

  35. 35.

    Thijssen JH, Poortman J, Schwarz F. Androgens in postmenopausal breast cancer: excretion, production and interaction with estrogens. J Steroid Biochem 1975; 6: 729–34.

    PubMed  CAS  Article  Google Scholar 

  36. 36.

    Kuller LH, Gutai JP. Re: A prospective study of endogenous estrogens and breast cancer in postmenopausal women. JNCI 1995; 87: 1414–5.

    PubMed  CAS  Google Scholar 

  37. 37.

    Malarkey WB, Schroeder LL, Stevens VC, James AG, Lanese RR. Twenty-four-hour preoperative endocrine profiles in women with benign and malignant breast disease. Cancer Res 1977; 37: 4655–9.

    PubMed  CAS  Google Scholar 

  38. 38.

    Drafta D, Schindler AE, Milcu SM, et al. Plasma hormones in pre-and postmenopausal breast cancer. J Steroid Biochem 1980; 13: 793–802.

    PubMed  CAS  Article  Google Scholar 

  39. 39.

    Bird CE, Cook S, Owen S, Sterns EE, Clark AF. Plasma concentrations of C-19 steroids, estrogens, FSH, LH and prolactin in post-menopausal women with and without breast cancer. Oncology 1981; 38: 365–8.

    PubMed  CAS  Article  Google Scholar 

  40. 40.

    Secreto G, Recchione C, Cavalleri A, Miraglia M, Dati V. Circulating levels of testosterone, 17 beta-oestradiol, luteinising hormone and prolactin in postmenopausal breast cancer patients. Br J Cancer 1983; 47: 269–75.

    PubMed  CAS  Google Scholar 

  41. 41.

    Reed MJ, Beranek PA, Cheng RW, Ghilchik MW, James VH. The distribution of oestradiol in plasma from postmenopausal women with or without breast cancer: relationships with metabolic clearance rates of oestradiol. Int J Cancer1985; 35: 457–60.

    PubMed  CAS  Google Scholar 

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Correspondence to Hollie V. Thomas.

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Thomas, H.V., Reeves, G.K. & Key, T.J. Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 8, 922 (1997). https://doi.org/10.1023/A:1018476631561

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  • Breast cancer
  • estrogen
  • postmenopausal
  • review
  • women