Hormone Replacement Therapy and Breast Cancer: Still More Questions Than Answers

  • Susan Love
Part of the Medical Science Symposia Series book series (MSSS, volume 17)


Estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) have been suspected of increasing breast cancer risk for decades. Despite many observational studies the topic is still unsettled [1].


Breast Cancer Breast Cancer Risk Hormone Replacement Therapy Estrogen Replacement Therapy Increase Breast Cancer Risk 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bush TL, Whiteman M, Flaws JA. Hormone replacement therapy and breast cancer: A qualitative review. Obstet Gynecol 2001;98:498–508.PubMedCrossRefGoogle Scholar
  2. 2.
    Hulley S, Grady D, Bush TL, et al. Randomized trial of estrogen plus progestin for the secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280:605–13.PubMedCrossRefGoogle Scholar
  3. 3.
    Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, et al. A prospective study of endogenous estrogens and breast cancer in potmenopausal women. J Natl Cancer Inst 1995;87:190–97.PubMedCrossRefGoogle Scholar
  4. 4.
    Pike MC, Krailo MD, Henderson BE, Casagrande JT, Hoel DG. “Hormonal” risk factors, “breast tissue age” and the age-incidence of breast cancer. Nature 1983;303:767–70.PubMedCrossRefGoogle Scholar
  5. 5.
    Rebbeck TR, Levin AM, Eisen A, et al Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst 1999;91(17);1475–79.PubMedCrossRefGoogle Scholar
  6. 6.
    Cauley JA, et al. Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Ann Intern Med 1999;130:270–77.PubMedGoogle Scholar
  7. 7.
    Lambe M, Hsieh C, Trichopoulos D, et al. Transient increase in risk of breast cancer after giving birth. N Engl J Med 1994;331:5–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Cauley J, Lucas F, Kuller L, et al. Bone mineral density and the risk of breast cancer in older women. The study of osteoporotic fractures. JAMA 1996;276:1404–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Zhang Y, Kiel D, Kreger B, et al. Bone mass and the risk of breast cancer among postmenopausal women. N Engl J Med 1997;336:611–17.PubMedCrossRefGoogle Scholar
  10. 10.
    Verbeek ALM, Hendricks, JHCL, Peeters PHM, Sturmans F. Mammographic breast pattern and the risk of breast cancer. Lancet 1984;1:591–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Stomper PC, Van Voorhis BJ, Ravnikar VA, Meyer JE. Mammographic changes associated with postmenopausal hormone replacement therapy: A longitudinal study. Radiology 1990;174:487–90.PubMedGoogle Scholar
  12. 12.
    Atkinson C, Warren R, Bingham SA, Day NE. Mammographic patterns as a predictive biomarker of breast cancer risk: effect of tamoxifen. Can Epid Bio Prev 1999;8:863–66.Google Scholar
  13. 13.
    Huang Z, Hankinson SE, Colditz GA, et al. Dual effects of weight and weight gain on breast cancer risk. JAMA 1997;278:1407–11.PubMedCrossRefGoogle Scholar
  14. 14.
    Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996;347:1713–27.CrossRefGoogle Scholar
  15. 15.
    Titus-Ernstoff L, Hatch EE, Hoover RN, et al. Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy. Br J Cancer 2001;84:126–33.PubMedCrossRefGoogle Scholar
  16. 16.
    Fisher B, Constantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P1 Study. J Natl Cancer Inst. 1998;90:1371–88.PubMedCrossRefGoogle Scholar
  17. 17.
    Cummings SR, Eckert S, Krueger KA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: Results from the MORE trial. JAMA 1999;281:2189–97.PubMedCrossRefGoogle Scholar
  18. 18.
    Cummings SR, et al. Estradiol level in postmenopausal women may indicate who benefits most from treatment to reduce risk of breast cancer. Annual Meeting of the American Society for Bone and Mineral Research, Toronto Sept 11, 2000.Google Scholar
  19. 19.
    Dupont WD, Page DL. Menopausal estrogen replacement therapy and breast cancer. Arch Intern Med 1991;151:67–72.PubMedCrossRefGoogle Scholar
  20. 20.
    Steinberg KK, Thacker SB, Smith SJ, et al. A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. JAMA 1991;262(15): 1985–90.CrossRefGoogle Scholar
  21. 21.
    Grady D, Ernster V. Invited commentary: Does hormone replacement therapy cause breast cancer? Am J Epidemiol 1991;134:1396–1400.Google Scholar
  22. 22.
    Sillero-Arenas M, Delgado-Rodriguez M, Rodigues-Canteras R, Bueno-Cavanillas A, Galvez-Vargas R. Menopausal hormone replacement therapy and breast cancer: A metaanalysis. Obstet Gynecol 1992;79:286–94.PubMedGoogle Scholar
  23. 23.
    Colditz GA, Egan KM, Stampfer MJ. Hormone replacement therapy and risk of breast cancer: Results from epidemiologic studies. Am J Obstet Gynecol 1993;168:1473–80.PubMedGoogle Scholar
  24. 24.
    Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: Collaborative reanalysis from SI epidemiological studies of 52705 women with breast cancer and 108411 women without breast cancer. Lancet 1997;350;1047–1060.CrossRefGoogle Scholar
  25. 25.
    Slujimer AV, Heineman MJ, DeJong FH, Evers JL. Endocrine activity of the postmenopausal ovary. Horm Res 1995;72:631.Google Scholar
  26. 26.
    Ettinger B, Pressman A, Sklarin P, Bauer DC, Cauley JA, Cummings SR. Associations between low levels of serum estradiol, bone density and fractures among elderly women: The study of osteoporotic fractures. J Clin Endocrinol Metab 1998;83:2239–43.PubMedCrossRefGoogle Scholar
  27. 27.
    Colditz GA, Hankinson SE, Hunter DJ, et al The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 1995;332:1589–93.PubMedCrossRefGoogle Scholar
  28. 28.
    Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA;283:485–91.Google Scholar
  29. 29.
    Ross RK, Paganini-Hill A, Wan PC, Pike MC. Effect of hormone replacement therapy on breast cancer risk:estrogen versus estrogen plus progestin. J Natl Cancer Inst 2000;92:328–32.PubMedCrossRefGoogle Scholar
  30. 30.
    Brinton LA, Brogan DR, Coates RJ, et al. Breast cancer risk among women under 55 years of age by joint usage of oral contraceptives and hormone replacement therapy. Menopause 1998;5:145–51.PubMedGoogle Scholar
  31. 31.
    Early Breast Cancer Trialists’ Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 1992;339:1–15.Google Scholar
  32. 32.
    Klijn JG, Blarney RW, Boccardo F, et al. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol 2001;19: 343–53.PubMedGoogle Scholar
  33. 33.
    Kuerer HM, Buzdar AU, Singletary SE. Biological basis and evolving role of aromatase inhibitors in the management of invasive carcinoma of the breast. J Surg Oncol 2001;77: 139–47.PubMedCrossRefGoogle Scholar
  34. 34.
    Beral V, Reeves G. Childbearing, oral contraceptive use, and breast cancer. Lancet 1993;341:1102.PubMedGoogle Scholar
  35. 35.
    Lethaby AE, O’Neill MA, Mason KE, et al. Overall survival from breast cancer in women pregnant or lactating at or after diagnosis. Int J Cancer 1996;67:751–55.PubMedCrossRefGoogle Scholar
  36. 36.
    Gelber S, Coates AS, Goldhirsch A, et al. Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer. J Clin Oncol 19:1671–75.Google Scholar
  37. 37.
    Bergkvist L, Adami HO, Persson I, et al Prognosis after breast cancer diagnosis in owmen exposed to estrogen and estrogen-progestin replacement therapy. Am J Epi 1980;130:221–27.Google Scholar
  38. 38.
    Col NF, Hirota LK, Orr RK, Erban JK, Wong JB, Lau J. Hormone replacement therapy after breast cancer: a systemic review and quantitative assessment of risk. J Clin Oncol 2001;19:2357–63.PubMedGoogle Scholar
  39. 39.
    O’Meara ES, Rossing MA, Daling JR, Elmore JG, Barlow WE, Weiss NS. Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality. J Natl Cancer Inst 2001;93:754–62.PubMedCrossRefGoogle Scholar
  40. 40.
    Fisher B, Dignam J, Bryant J, et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 1996;88:1529–42.PubMedCrossRefGoogle Scholar
  41. 41.
    Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: An overview of the randomized trials. Lancet 1998;351:1451–67.CrossRefGoogle Scholar
  42. 42.
    Byrne C, Connolly JL, Colditz GA, Schnitt SJ. Biopsy confirmed benign breast disease postmenopausal use of exogenous female hormones and breast cancer risk. Cancer 2000; 89:2046–52.PubMedCrossRefGoogle Scholar
  43. 43.
    Jernstrom H, Lerman C, Ghadirian P, et al. Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2. Lancet 1999;354:1846–50.PubMedCrossRefGoogle Scholar
  44. 44.
    King, MC, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-Pl)Breast Cancer Prevention Trial. JAMA 2001;286:2251–56.PubMedCrossRefGoogle Scholar
  45. 45.
    Kuiper GG, Enmark E, Pelto-Huikko M, Nillson S, Gutafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci 1996;93:5925–30.PubMedCrossRefGoogle Scholar
  46. 46.
    Horwitz KB, Sartorius CA, Hovland AR, et al. Surprises with anti porgestins: Novel mechanisms of progesterone receptor action. Ciba Foundation Symposium 1995;191:235–49; (discussion) 250–53.PubMedGoogle Scholar
  47. 47.
    McKenna NJ, O’Malley BW. An issue of tissues: Divining the split personalities of selective estrogen receptor modulators. Nat Med 2000;6:960–62.PubMedCrossRefGoogle Scholar
  48. 48.
    Chetrite GS, Cortes-Prieto J, Phillippe JC, et al. Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol 2000;72:23–27.PubMedCrossRefGoogle Scholar
  49. 49.
    Bhatnagar AS, Brodie AM, Long BJ, Evans DB, Miller WR. Intracellular aromatase and its relevance to the pharmacological efficacy of aromatase inhibitors. J Steroid Biochem Mol Biol 2001;76:199–202.PubMedCrossRefGoogle Scholar
  50. 50.
    Petrakis NL, Wrensch MR, Ernster VL, et al. Influence of pregnancy and lactation on serum and breast fluid estrogen levels: Implications for breast cancer risk. In J Cancer 1987:40(5):587–91.Google Scholar
  51. 51.
    Veronesi U, Luini A, Mariani L, et al. Effect of menstrual phase on surgical treatment of breast cancer. Lancet 1994;343:1545–47.PubMedCrossRefGoogle Scholar
  52. 52.
    Rajkumar L, Guzman RC, Yang J, Thordarson G, Talamantes F, Nandi S. Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis. Proc Natl Acad Sci 2001;98(20):11755–59.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Susan Love

There are no affiliations available

Personalised recommendations