American Journal of Cancer

, Volume 1, Issue 3, pp 173–178

Breast Cancer Prevention

The Risks and Benefits of Drug Therapy
Leading Article


Although screening recommendations have been long established, more than 40 000 women died of breast cancer in the US in the year 2001. Risk factors for developing breast cancer have been identified, leading to the possibility of breast cancer prevention. Adjuvant tamoxifen for 5 years decreases the incidence of contralateral breast cancer by 50%. This finding and the favorable safety profile of tamoxifen led to the NSABP P-1 trial, which demonstrated a 50% reduction of breast cancer in a high-risk population. The benefit was seen only in estrogen receptor (ER)-positive breast cancers, but was seen in all age groups. Furthermore, tamoxifen was found to reduce the overall rate of osteoporotic fractures. Endometrial cancer in the tamoxifen arm of the NSABP P-l trial was increased 3- to 4-fold in women >50 years, similar to the increased risk seen with adjuvant tamoxifen therapy. Other agents that are currently under study for breast cancer chemoprevention include raloxifene and retinoids. The STAR trial is under way and compares raloxifene to tamoxifen for breast cancer chemoprevention in high-risk women. Tamoxifen is currently the only agent approved by the US Food and Drug Administration (FDA) for chemoprevention in breast cancer but has not produced a survival advantage to date.


  1. 1.
    Greenlee RT, Hill-Hamon MB, Murray T, et al. Cancer Statistics, 2001. CA Cancer J Clin 2001; 51: 15–36PubMedCrossRefGoogle Scholar
  2. 2.
    Tokunaga M, Land CE, Yamamoto T, et al. Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950–1980. Radiat Res 1987; 112: 243–72PubMedCrossRefGoogle Scholar
  3. 3.
    Hildreth NG, Shore RE, Dvoretsky PM. The risk of breast cancer after irradiation of the thymus in infancy. N Engl J Med 1989; 321: 1281–4PubMedCrossRefGoogle Scholar
  4. 4.
    Miller AB, Howe GR, Sherman GJ, et al. Mortality from breast cancer after irradiation during fluoroscopic examinations in patients being treated for tuberculosis. N Engl J Med 1989; 321: 1285–9PubMedCrossRefGoogle Scholar
  5. 5.
    Jordan VC, Costa AF. Chemoprevention. In: Harris JR, editor. Diseases of the Breast. 2nd ed. Philadelphia (PA): Lippincott Williams & Wilkins, 2000Google Scholar
  6. 6.
    Wickerham DL, Tan-Chiu E. Breast cancer chemoprevention: current status and future directions. Semin Oncol 2001; 28: 253–9PubMedCrossRefGoogle Scholar
  7. 7.
    Rose DP. Dietary Fat, Fatty Acids and Breast Cancer. Breast Cancer 1997; 4: 7–16PubMedCrossRefGoogle Scholar
  8. 8.
    Schairer C, Lubin J, Troisi R, et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 2000; 283: 485–91PubMedCrossRefGoogle Scholar
  9. 9.
    Dorgan JF, Baer DJ, Albert PS, et al. Serum hormones and the alcohol-breast cancer association in postmenopausal women. J Natl Cancer Inst 2001; 93: 710–5PubMedCrossRefGoogle Scholar
  10. 10.
    Hunter DJ, Spiegelman D, Adami HO, et al. Cohort studies of fat intake and the risk of breast cancer: a pooled analysis. N Engl J Med 1996; 334: 356–61PubMedCrossRefGoogle Scholar
  11. 11.
    Gail MH, Brinton LA, Byar DP, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989; 81: 1879–86PubMedCrossRefGoogle Scholar
  12. 12.
    Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999; 340: 77–84PubMedCrossRefGoogle Scholar
  13. 13.
    Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2001; 345: 159–64PubMedCrossRefGoogle Scholar
  14. 14.
    Meijers-Heijboer EJ, Verhoog LC, Brekelmans CT, et al. Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation. Lancet 2000; 355: 2015–20PubMedCrossRefGoogle Scholar
  15. 15.
    Schairer C, Persson I, Falkeborn M, et al. Breast cancer risk associated with gynecologic surgery and indications for such surgery. Int J Cancer 1997; 70: 150–4PubMedCrossRefGoogle Scholar
  16. 16.
    Meijer WJ, van Lindert AC. Prophylactic oophorectomy. Eur J Obstet Gynecol Reprod Biol 1992; 47: 59–65PubMedCrossRefGoogle Scholar
  17. 17.
    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: 1475–9PubMedCrossRefGoogle Scholar
  18. 18.
    Early Breast Cancer Trialists’ Collaborative Group. Ovarian ablation in early breast cancer: overview of the randomised trials. Lancet 1996; 348: 1189–96CrossRefGoogle Scholar
  19. 19.
    Lotan R. Retinoids in cancer chemoprevention. FASEB J 1996; 10: 1031–9PubMedGoogle Scholar
  20. 20.
    Jordan VC, Lababidi MK, Mirecki DM. Anti-oestrogenic and anti-tumour properties of prolonged tamoxifen therapy in C3H/OUJ mice. Eur J Cancer 1990; 26: 718–21PubMedCrossRefGoogle Scholar
  21. 21.
    Jordan VC, Lababidi MK, Langan-Fahey S. Suppression of mouse mammary tumorigenesis by long-term tamoxifen therapy. J Natl Cancer Inst 1991; 83: 492–6PubMedCrossRefGoogle Scholar
  22. 22.
    O’Regan RM, Jordan VC. Tamoxifen to raloxifene and beyond. Semin Oncol 2001; 28: 260–73PubMedCrossRefGoogle Scholar
  23. 23.
    Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998; 351: 1451–67CrossRefGoogle Scholar
  24. 24.
    Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90: 1371–88PubMedCrossRefGoogle Scholar
  25. 25.
    King M. Special Presentation. American Society of Clinical Oncology (ASCO) Annual Meeting; 2001 May 12–15; San Francisco. San Francisco (CA): American Society of Clinical Oncology, 2001Google Scholar
  26. 26.
    Robson M, Gilewski T, Haas B, et al. BRCA-associated breast cancer in young women. J Clin Oncol 1998; 16: 1642–9PubMedGoogle Scholar
  27. 27.
    Powles T, Eeles R, Ashley S, et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 1998; 352: 98–101PubMedGoogle Scholar
  28. 28.
    Veronesi U, Maisonneuve P, Costa A, et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet 1998; 352: 93–7PubMedGoogle Scholar
  29. 29.
    Turner RT, Wakley GK, Hannon KS, et al. Tamoxifen prevents the skeletal effects of ovarian hormone deficiency in rats. J Bone Miner Res 1987; 2: 449–56PubMedCrossRefGoogle Scholar
  30. 30.
    Love RR, Mazess RB, Barden HS, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992; 326: 852–6PubMedCrossRefGoogle Scholar
  31. 31.
    Kristensen B, Ejlertsen B, Dalgaard P, et al. Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: a randomized study. J Clin Oncol 1994; 12: 992–7PubMedGoogle Scholar
  32. 32.
    Love RR, Wiebe DA, Feyzi JM, et al. Effects of tamoxifen on cardiovascular risk factors in postmenopausal women after 5 years of treatment. J Natl Cancer Inst 1994; 86: 1534–9PubMedCrossRefGoogle Scholar
  33. 33.
    Bruning PF, Bonfrer JM, Hart AA, et al. Tamoxifen, serum lipoproteins and cardiovascular risk. Br J Cancer 1988; 58: 497–9PubMedCrossRefGoogle Scholar
  34. 34.
    Grey AB, Stapleton JP, Evans MC, et al. The effect of the anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women. J Clin Endocrinol Metab 1995; 80: 3191–5PubMedCrossRefGoogle Scholar
  35. 35.
    Saarto T, Blomqvist C, Ehnholm C, et al. Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer. J Clin Oncol 1996; 14: 429–33PubMedGoogle Scholar
  36. 36.
    Early Breast Cancer Trialists’ Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Lancet 1992; 339: 1–15Google Scholar
  37. 37.
    Rutqvist LE, Mattsson A. Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen: the Stockholm Breast Cancer Study Group. J Natl Cancer Inst 1993; 85: 1398–406PubMedCrossRefGoogle Scholar
  38. 38.
    McDonald CC, Stewart HJ. Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial: the Scottish Breast Cancer Committee. BMJ 1991; 303: 435–7PubMedCrossRefGoogle Scholar
  39. 39.
    Costantino JP, Kuller LH, Ives DG, et al. Coronary heart disease mortality and adjuvant tamoxifen therapy. J Natl Cancer Inst 1997; 89: 776–82PubMedCrossRefGoogle Scholar
  40. 40.
    Bernstein L, Deapen D, Cerhan JR, et al. Tamoxifen therapy for breast cancer and endometrial cancer risk. J Natl Cancer Inst 1999; 91: 1654–62PubMedCrossRefGoogle Scholar
  41. 41.
    Paganini-Hill A, Clark LJ. Eye problems in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat 2000; 60(2): 167–72PubMedCrossRefGoogle Scholar
  42. 42.
    Gottardis MM, Jordan VC. Antitumor actions of keoxifene and tamoxifen in the N-nitrosomethylurea-induced rat mammary carcinoma model. Cancer Res 1987; 47: 4020–4PubMedGoogle Scholar
  43. 43.
    Anzano MA, Peer CW, Smith JM, et al. Chemoprevention of mammary carcinogenesis in the rat: combined use of raloxifene and 9-cis-retinoic acid. J Natl Cancer Inst 1996; 88: 123–5PubMedCrossRefGoogle Scholar
  44. 44.
    Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337: 1641–7PubMedCrossRefGoogle Scholar
  45. 45.
    Cummings SR, Eckert S, Krueger KA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 1999; 281: 2189–97PubMedCrossRefGoogle Scholar
  46. 46.
    Jordan VC, Glusman JE, Eckert S, et al. Incident primary breast cancers are reduced by raloxifene: Integrated data fom multicenter, double-blind, randomized trials in ∼12,000 postmenopausal women [abstract 466]. Proc Am Soc Clin Oncol 1998; 17: 122aGoogle Scholar
  47. 47.
    Black LJ, Sato M, Rowley ER, et al. Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J Clin Invest 1994; 93: 63–9PubMedCrossRefGoogle Scholar
  48. 48.
    O’Regan RM, Gajdos C, Dardes R, et al. Effects of raloxifene after tamoxifen on breast and endometrial cancer growth [abstract]. Proc Am Soc Clin Oncol 2001; 20: 95Google Scholar
  49. 49.
    Jordan VC, Morrow M. Tamoxifen, raloxifene, and the prevention of breast cancer. Endocr Rev 1999; 20(3): 253–78PubMedCrossRefGoogle Scholar
  50. 50.
    Moon RC, Grubbs CJ, Sporn MB. Inhibition of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis by retinyl acetate. Cancer Res 1976; 36: 2626–30PubMedGoogle Scholar
  51. 51.
    Nabholtz JM, Buzdar A, Pollak M, et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol 2000; 18: 3758–67PubMedGoogle Scholar
  52. 52.
    Mouridsen H, Gershanovich M, Sun Y, et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001; 19: 2596–606PubMedGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  1. 1.Division of Hematology/OncologyNorthwestern UniversityChicagoUSA

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