Advertisement

Response and Resistance to the Endocrine Prevention of Breast Cancer

  • Anthony Howell
  • Nigel J. Bundred
  • Jack Cuzick
  • D. Craig Allred
  • Robert Clarke
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Current endocrine approaches to breast cancer (BC) prevention are targeted mainly at the estrogen receptor alpha (ERα) (1). Endocrine prevention depends upon either reducing the concentration of estrogen reaching ERα+ breast epithelial cells [estrogen deprivation (ED)] by, for example, ovarian suppression in premenopausal women, or aromatase inhibition in postmenopausal women, or by blocking the interaction of estrogen with ERα by selective estrogen receptor modulators (SERMs) such as tamoxifen (Tarn) and raloxifene (Ral). Observational studies (2–11) and randomised controlled trials (12–25) indicate that treatment by ED and SERMS reduces the risk of subsequent BC by approximately 50% and that this effect is prolonged (16, 18, 20, 26). In the human breast, ERα is detectable in epithelial cells of lobules and ducts and not in the stroma (27). However, it is not clear whether normal, premalignant or malignant epithelial cells are the targets for endocrine prevention. In this chapter, we summarise the results of endocrine prevention trials to date and what is known about the response of the three types of potential target structures to estrogen stimulation and inhibition by ED and SERMS.

Keywords

Breast Cancer Breast Cancer Contralateral Breast Cancer Premalignant Lesion Endocrine Prevention 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Howell A, Clarke RB, Evans G, et al. Estrogen deprivation for breast cancer prevention. Recent Results Cancer Res (in press).Google Scholar
  2. 2.
    Feinleib M (1968) Breast cancer and artificial menopause: a cohort study. J Natl Cancer Inst 41: 315–329.PubMedGoogle Scholar
  3. 3.
    Hirayama T, Wynder EL (1962) A study of the epidemiology of cancer of the breast II. The influence of hysterectomy, Cancer 5: 28–38.PubMedCrossRefGoogle Scholar
  4. 4.
    Trichopoulos D, MacMahon B, Cole P (1972) Menopause and breast cancer risk. J Natl Cancer Inst 48: 605–613.PubMedGoogle Scholar
  5. 5.
    Narod SA, Brunet JS, Ghadirian P, et al. (2000) Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case control study. Hereditary Breast Cancer Clinical Study Group, Lancet 356: 1876–1881.Google Scholar
  6. 6.
    Gronwald J, Tung N, Foulkes WD, et al. (2006) Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer 118: 2281–2284.PubMedCrossRefGoogle Scholar
  7. 7.
    Rebbeck TR, Lynch HT, Neuhausen SL (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346: 1616–1622.PubMedCrossRefGoogle Scholar
  8. 8.
    Kauff ND, Satagopan JM, Robson ME, et al. (2002) Risk reducing salpino-oophorectomy in women with a BRCA1 and BRCA2 mutation. N Engl J Med 346: 1609–1615.PubMedCrossRefGoogle Scholar
  9. 9.
    Metcalfe K, Lynch HT, Ghadirian P, et al. (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 22: 2328–2335.PubMedCrossRefGoogle Scholar
  10. 10.
    Olson JE, Sellers TA, Iturria SJ, et al. (2004) Bilateral oophorectomy and breast cancer risk reduction among women with a family history. Cancer Detect Prev 28: 357–360.PubMedCrossRefGoogle Scholar
  11. 11.
    Eisen A, Lubinski J, Klijn J, et al. (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case control study. J Clin Oncol 23: 7491–7496.PubMedCrossRefGoogle Scholar
  12. 12.
    Cuzick J, Baum M (1985) Tamoxifen and contralateral breast cancer. Lancet 2: 282.PubMedCrossRefGoogle Scholar
  13. 13.
    Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15 year survival: an overview of the randomised trials. Lancet 365: 1687–1717.CrossRefGoogle Scholar
  14. 14.
    Cuzick J (2005) Aromatase inhibitors for breast cancer prevention. J Clin Oncol 23: 1636–1643.PubMedCrossRefGoogle Scholar
  15. 15.
    Powles TJ, Eeles R, Ashley S, et al. (1998) Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 352: 98–101.PubMedGoogle Scholar
  16. 16.
    Powles TJ, Ashley S, Tidy VA, et al. 20 year follow up of the Royal Marsden tamoxifen breast cancer prevention trial. JNCI (in press).Google Scholar
  17. 17.
    Cuzick J, Forbes J, Edwards R, et al. (2002) First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet 360: 817–824.PubMedCrossRefGoogle Scholar
  18. 18.
    Cuzick J, Sestak I, Forbes J, et al. Long-term results of tamoxifen prophylaxis for breast cancer–96 month follow up of the IBIS-I study, JNCI (in press).Google Scholar
  19. 19.
    Fisher B, Costantino JP, Wickerham DL, et al. (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. JNCI 90: 1371–1388.PubMedCrossRefGoogle Scholar
  20. 20.
    Fisher B, Costantino JP, Wickerham DL, et al. (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. JNCI 97: 1652–1662.PubMedGoogle Scholar
  21. 21.
    Cummings SR, Eckert S, Krueger KA (1999) The effect of Raloxifene on risk of breast cancer in postmenopausal women. Results from the MORE randomised trial. JAMA 281: 2189–2197.PubMedCrossRefGoogle Scholar
  22. 22.
    Martino S, Cauley JA, Barrett-Connor E, et al. (2004) Continuing outcomes relevant to evista: breast cancer incidence in postmenopausal osteoporotic women in a randomised trial of raloxifene. JNCI 96: 1751–1761.PubMedGoogle Scholar
  23. 23.
    Barrett-Connor E, Mosca L, Collins P, et al. (2006) Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 355: 125–137.PubMedCrossRefGoogle Scholar
  24. 24.
    Vogel VG, Costantino JP, Wickerham DL, et al. (2006) Effects of tamoxifen v raloxifene on the risk of developing invasive breast cancer and other disease outcomes. The NSABP study of tamoxifen and raloxifene (STAR) P-2 trial, JAMA 295: 2727–2741.PubMedCrossRefGoogle Scholar
  25. 25.
    Cuzick J, Powles T, Veronesi U, et al. (2003) Overview of the main outcomes in breast cancer prevention trials. Lancet 361: 296–300.PubMedCrossRefGoogle Scholar
  26. 26.
    Pike MC, Spicer DV (1993) The chemoprevention of breast cancer by reducing sex steroid exposure: perspectives from epidemiology. J Cell Biochem Suppl 17G: 26–36.PubMedCrossRefGoogle Scholar
  27. 27.
    Clarke RB, Howell A, Potten CS, et al. (1997) Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res 57: 4987–4991.PubMedGoogle Scholar
  28. 28.
    Shaaban AM, Sloane JP, West CR, et al. (2002) Breast cancer risk in usual ductal hyperplasia is defined by estrogen receptor-α and Ki-67 expression. Am J Pathol 160: 597–604.PubMedGoogle Scholar
  29. 29.
    Dessauvagie BF, Zhao W, Heel-Miller KA, et al. (2006) Characterisation of columnar cell lesions of the breast: immunophenotypic analysis of columnar alteration of lobules with prominent apical snouts and secretions. Hum Pathol 38: 284–292.PubMedCrossRefGoogle Scholar
  30. 30.
    Bramley M, Clarke RB, Howell A, et al. (2006) Effects of oestrogens and anti-oestrogens on normal breast tissue from women bearing BRCA1 and BRCA2 mutations. Br J Cancer 94: 1021–1028.PubMedCrossRefGoogle Scholar
  31. 31.
    Shoker BS, Jarvis C, Clarke RB, et al. (1999) Estrogen receptor-positive proliferating cells in the normal and precancerous breast. Am J Pathol 155: 1811–1815.PubMedGoogle Scholar
  32. 32.
    Lee S, Mohsin SK, Mao S, et al. (2005) Hormones, receptors and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer. Breast Cancer Res 8: 1–9.Google Scholar
  33. 33.
    Zavagno G, Meggiolaro F, Pluchinotta A, et al. (2000) Influence of age and menopausal status on pathologic and biologic features of breast cancer. Breast 9: 320–328.PubMedCrossRefGoogle Scholar
  34. 34.
    Wellings SR (1980) A hypothesis of the origin of human breast cancer from the terminal ductal lobular unit. Pathol Res Pract 515–535.Google Scholar
  35. 35.
    Wellings SR, Jensen HM, Marcum RG (1975) An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. JNCI 55: 231–273.PubMedGoogle Scholar
  36. 36.
    Kim H-J, Jung W-H, Kim D-Y, et al. (2000) Expression of cyclins in ductal hyperplasia, atypical ductal hyperplasia and ductal carcinoma in-situ of the breast. Yonsei Med J 41: 345–353.PubMedGoogle Scholar
  37. 37.
    Allred DC, Mohsin SK, Fuqua SAW (2001) Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer 8: 47–61.PubMedCrossRefGoogle Scholar
  38. 38.
    Potten CS, Watson RJ, Williams GT, et al. (1988) The effect of age and menstrual cycle upon proliferative activity of the normal human breast. Br J Cancer 58: 163–170.PubMedGoogle Scholar
  39. 39.
    Laidlaw IJ, Clarke RB, Howell A, et al. (1995) The proliferation of normal human breast tissue implanted into athymic nude mice is stimulated by estrogen but not progesterone. Endocrinology 136: 164–171.PubMedCrossRefGoogle Scholar
  40. 40.
    Battersby S, Anderson T (1988) Proliferative and secretory activity in the pregnant and lactating human breast. Virchows Archiv A Pathol Anat 413: 189–196.CrossRefGoogle Scholar
  41. 41.
    Feuerhake F, Sigg W, Hofter EA, et al. (2003) Cell proliferation, apoptosis and expression of bcl-2 and Bax in non-lactating human breast epithelium in relation to the menstrual cycle and reproductive history. Breast Cancer Res Treat 77: 37–48.PubMedCrossRefGoogle Scholar
  42. 42.
    Williams G, Anderson E, Howell A, et al. (1991) Oral contraceptive (OCP) use increases proliferation and decreases oestrogen receptor content of epithelial cells in the normal human breast. Int J Cancer 48: 206–210.PubMedCrossRefGoogle Scholar
  43. 43.
    Hargreaves DF, Knox F, Swindell R, et al. (1998) Epithelial proliferation and hormone receptor status in the normal postmenopausal breast and the effects of hormone replacement therapy. Br J Cancer 78: 945–949.PubMedGoogle Scholar
  44. 44.
    Dobson RRH, Chan CK, Knox F, et al. (2000) The effects of prolonged HRT treatment in normal postmenopausal breast epithelium. Breast Cancer Res Treat 64: 106.Google Scholar
  45. 45.
    Hofseth LJ, Raafat AM, Osuch JR, et al. (1999) Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast. J Clin Endo Metab 84: 4559–4565.CrossRefGoogle Scholar
  46. 46.
    Harper-Wynne C, Ross G, Sacks N, et al. (2002) Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention. Cancer Epidemiol Biomarkers Prev 11: 614–621.PubMedGoogle Scholar
  47. 47.
    Walker KJ, Price-Thomas JM, Candlish W, et al. (1991) Influence of the antioestrogen tamoxifen on normal breast tissue. Br J Cancer 64: 764–768.PubMedGoogle Scholar
  48. 48.
    de Lima GR, Facina G, Shida JY, et al. (2003) Effects of low dose tamoxifen on normal breast tissue from premenopausal women. Eur J Cancer 39: 891–898.PubMedCrossRefGoogle Scholar
  49. 49.
    Bernardes JR Jr, Nonogaki S, Seixas MT, et al. (1999) Effect of a half dose of tamoxifen on proliferative activity in normal breast tissue. Int J Gynaecol Obstet 67: 33–38.PubMedCrossRefGoogle Scholar
  50. 50.
    Borges da Silva B, Lopes IMS, Gebrim LH (2006) Effects of raloxifene on normal breast tissue from premenopausal women. Breast Cancer Res Treat 95: 99–103.CrossRefGoogle Scholar
  51. 51.
    Holland PA, Knox WF, Potten CS, et al. (1997) Assessment of hormone dependence of comedo ductal carcinoma in-situ of the breast. JNCI 89: 1059–1064.PubMedCrossRefGoogle Scholar
  52. 52.
    Gandhi A, Holland PA, Knox WF, et al. (2000) Effects of a pure antiestrogen on apoptosis and proliferation within human breast ductal carcinoma in-situ. Cancer Res 60: 4284–4288.PubMedGoogle Scholar
  53. 53.
    Boland GP, McKeown A, Chan KC, et al. (2003) Biological response to hormonal manipulation in oestrogen receptor positive ductal carcinoma in-situ of the breast. Br J Cancer 89: 277–283.PubMedCrossRefGoogle Scholar
  54. 54.
    Mohsin SK, Allred DC, Osborne CK, et al. (2005) Morphological and immunophenotypic markers as surrogate endpoints of tamoxifen effect for prevention of breast cancer. Breast Cancer Res Treat 94: 205–211.PubMedCrossRefGoogle Scholar
  55. 55.
    Prasad R, Boland GP, Cramer A, et al. (2003) Short term biologic response to withdrawal of hormone replacement therapy in patients with invasive breast carcinoma. Cancer 98: 2539–2546.PubMedCrossRefGoogle Scholar
  56. 56.
    Geisler J (2003) Breast cancer tissue estrogens and their manipulation with aromatase inhibitors and inactivators. J Steroid Biochem Mol Biol 86: 245–253.PubMedCrossRefGoogle Scholar
  57. 57.
    Geisler J, Detre S, Berntsen H, et al. (2001) Influence of neoadjuvant anastrozole (arimidex) on intratumoral estrogen levels and proliferation markers in patients with locally advanced breast cancer. Clin Cancer Res 7: 1230–1236.PubMedGoogle Scholar
  58. 58.
    Miller WR, White S, Dixon JM, et al. (2006) Proliferation, steroid receptor and clinical/pathological response in breast cancer treated with letrozole. Br J Cancer 94: 1051–1056.PubMedCrossRefGoogle Scholar
  59. 59.
    Dowsett M, Ebbs SR, Dixon JM, et al. (2005) Biomarker changes during neoadjuvant anastrozole, tamoxifen or the combination: influence of hormonal status and HER-2 in breast cancer – a study from the IMPACT trialists. J Clin Oncol 23: 2477–2492.PubMedCrossRefGoogle Scholar
  60. 60.
    Dowsett M, Bundred NJ, Decensi A, et al. (2001) Effect of raloxifene on breast cancer cell Ki-67 and apoptosis: a double-blind, placebo-controlled, randomised clinical trial in postmenopausal patients. Cancer Epidemiol Biomarkers Prev 10: 961–966.PubMedGoogle Scholar
  61. 61.
    Robertson JF, Nicholson RI, Bundred NJ, et al. (2001) Comparison of the short term biological effects of 7α-[9-(4, 4, 5, 5, 5-pentafluoropentylsulfinyl)-nonyl]estra-1, 3, 5, (10)-triene-3, 17β-diol (faslodex) versus tamoxifen in postmenopausal women with primary breast cancer. Cancer Res 61: 6739–6746.PubMedGoogle Scholar
  62. 62.
    Stefanick ML, Anderson GL, Margolis KL, et al. (2006) Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 295: 1647–1657.PubMedCrossRefGoogle Scholar
  63. 63.
    Kotsopoulos J, Lubinski J, Neuhausen SL, et al. (2006) Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Gynecol Oncol 100: 83–88.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Anthony Howell
    • 1
  • Nigel J. Bundred
  • Jack Cuzick
    • 2
  • D. Craig Allred
  • Robert Clarke
    • 3
  1. 1.CRC Department Medical OncologyUniversity of Manchester Christie Hospital and Holt Radium Inst.ManchesterUK
  2. 2.Cancer Research UK Centre for Epidemiol., Mathematics, and StatisticsWolfson Institute of Preventive MedicineLondonUK
  3. 3.Breast Biology Group Division of Cancer StudiesUniversity of Manchester Christie Hospital (NHS) TrustManchester

Personalised recommendations