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Risk reduction of distant metastasis in hormone-sensitive postmenopausal breast cancer

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Abstract

Adjuvant endocrine therapy remains the principle strategy to reduce recurrence risk in postmenopausal women with early breast cancer. Studies of the natural history of breast cancer have shown that, while not reaching zero at any time point, the risk of recurrence is highest in the first 5 years following initial diagnosis and treatment. Within this initial 5 years, there is a peak of recurrence at the 2- to 3-year mark. Among the types of breast cancer recurrences observed at this early peak, distant metastasis (DM) predominates over local or contralateral relapse. DM recurrences are most strongly linked to breast-cancer-related death, and it has been suggested that adjuvant endocrine therapies that are most effective in minimizing the early peak of DM recurrence may have the most favorable impact on survival in women with early breast cancer. Aromatase inhibitors (AIs) including anastrozole, letrozole, and exemestane have gained popularity in the past few years as alternatives to 5 years of adjuvant tamoxifen, the previous standard of care. However, clinicians have not yet resolved how best to integrate AIs into breast cancer treatment; both upfront therapy (i.e., in lieu of tamoxifen) and a sequential/switch strategy (i.e., after some period of prior tamoxifen) have been proposed. The benefits and drawbacks of these approaches to AI treatment, particularly with respect to reducing early DM recurrences, are reviewed.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.

    Article  PubMed  Google Scholar 

  2. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle Pl. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007;8:581–92.

    Google Scholar 

  3. Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J, editors. Cancer incidence in five continents, vol VII. International Agency for Research on Cancer Scientific Publications No. 143. New York: Oxford University Press; 1999.

  4. Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S, Japan Public Health Center-Based Prospective Study on Cancer Cardiovascular Diseases Group. Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst. 2003;95:906–13.

    PubMed  CAS  Google Scholar 

  5. Ueda K, Tsukuma H, Tanaka H, Ajiki W, Oshima A. Estimation of individualized probabilities of developing breast cancer for Japanese women. Breast Cancer. 2003;10:54–62.

    Article  PubMed  Google Scholar 

  6. Minami Y, Tsubono Y, Nishino Y, Ohuchi N, Shibuya D, Hisamichi S. The increase of female breast cancer incidence in Japan: emergence of birth cohort effect. Int J Cancer. 2004;108:901–6.

    Article  PubMed  CAS  Google Scholar 

  7. Research Group for Population-Based Cancer Registration in Japan. Cancer incidence and incidence rates in Japan in 1995: estimates based on data from nine population-based cancer registries. Jpn J Clin Oncol. 2000;30:318–21.

    Article  Google Scholar 

  8. Adlercreutz CH, Goldin BR, Gorbach SL, Höckerstedt KA, Watanabe S, Hämäläinen EK, et al. Soybean phytoestrogen intake and cancer risk. J Nutr. 1995;125(3 Suppl):757S–70S (Erratum in: J Nutr. 1995;125:1960).

    PubMed  CAS  Google Scholar 

  9. Ueno M, Kiba T, Nishimura T, Kitano T, Yanagihara K, Yoshikawa K, et al. Changes in survival during the past two decades for breast cancer at the Kyoto University Hospital. Eur J Surg Oncol. 2007;33:696–9.

    PubMed  CAS  Google Scholar 

  10. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.

    Article  CAS  Google Scholar 

  11. Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol. 1996;14:2738–46.

    PubMed  CAS  Google Scholar 

  12. Lamerato L, Havstad S, Gandhi S, Jones D, Chlebowski R. Breast cancer recurrence and related mortality in US patients with early breast cancer. J Clin Oncol. 2005;23(16S):62s (Abstract 738).

    Google Scholar 

  13. Doughty JC, Wilson CR, Monypenny IJ, Skene AI, Abram P, Gattuso J, et al. Distant metastasis: the most common type of early recurrence with adjuvant tamoxifen therapy. Breast Cancer Res Treat. 2007;106(Suppl 1):S145 (Abstract 3057).

    Google Scholar 

  14. Aiello EJ, Buist DS, Wagner EH, Tuzzio L, Greene SM, Lamerato LE, et al. Diffusion of aromatase inhibitors for breast cancer therapy between 1996 and 2003 in the Cancer Research Network. Breast Cancer Res Treat. 2008;107:397–403.

    Article  PubMed  CAS  Google Scholar 

  15. Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, et al. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007;369:559–70 (Erratum in: Lancet. 2007;369:906).

    Article  PubMed  CAS  Google Scholar 

  16. Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, et al. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007;25:2664–70.

    Article  PubMed  CAS  Google Scholar 

  17. Hortobagyi GN, Kau S-W, Buzdar AU, Theriault RL, Booser DJ, Gwyn K, et al. What is the prognosis of patients with operable breast cancer (BC) five years after diagnosis? J Clin Oncol. 2004;22(14S):23 (Abstract 585).

    Google Scholar 

  18. Azria D, Tubiana-Hulin M, Spielmann M, Coudert B, Monnier A, Serin D, et al. Prognostic factor for early versus late relapse in non metastatic hormonodependent breast cancers (HBC) treated by tamoxifen. Breast Cancer Res Treat. 2006;100(Suppl 1):S272 (Abstract 6047).

    Google Scholar 

  19. Dignam JJ, Dukic VM, Anderson SJ, Mamounas EP, Jeong JH, Costantino JP. Time-dependent patterns of recurrence after early stage breast cancer: preliminary observations and methodological issues. J Clin Oncol. 2007;25(18S):11a (Abstract 536).

    Google Scholar 

  20. Lawrence G, Pritchard MG, Kearins O, Casey M. An analysis of breast cancer recurrences for screen detected and symptomatic breast cancers diagnosed in the West Midlands in 1996 and 1997. Breast Cancer Res Treat. 2005;94(Suppl 1):S211 (Abstract 5019).

    Google Scholar 

  21. Thames HD, Buchholz TA, Smith CD. Frequency of first metastatic events in breast cancer: implications for sequencing of systemic and local-regional treatment. J Clin Oncol. 1999;17:2649–58.

    PubMed  CAS  Google Scholar 

  22. Viale G, Biobbie-Hurder A, BIG Collaborative Group and International Breast Cancer Study Group (IBCSG). Value of centrally-assessed Ki-67 labeling index as a marker of prognosis and predictor of response to adjuvant endocrine therapy in the BIG 1–98 trial of postmenopausal women with estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2007;106(Suppl 1):S17 (Abstract 64).

    Google Scholar 

  23. Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell’Orto P, Del Curto B, Henriksen KL, et al. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1–98 randomised trial. Lancet Oncol. 2008;9:23–8.

    Article  PubMed  CAS  Google Scholar 

  24. Habel LA, Achacoso N, Maddala T, Alexander C, Baehner FL, Shak S, et al. Estrogen receptor and breast cancer survival in a Kaiser Permanente population-based study: comparison of quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Breast Cancer Res Treat. 2007;106(Suppl 1):S216 (Abstract 5029).

    Google Scholar 

  25. Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989;320:479–84.

    PubMed  CAS  Google Scholar 

  26. Rutqvist LE, Johansson H, Stockholm Breast Cancer Study Group. Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among postmenopausal patients with early stage breast cancer. Acta Oncol. 2007;46:133–45.

    Article  PubMed  CAS  Google Scholar 

  27. Debled M, MacGrogan G, Brouste V, Mathoulin-Pelissier S, Durand M, Mauriac L. Prognostic factors of early distant recurrence in hormone receptor-positive, postmenopausal breast cancer patients receiving adjuvant tamoxifen therapy: results of a retrospective analysis. Cancer. 2007;109:2197–204.

    Article  PubMed  CAS  Google Scholar 

  28. Kryj M, Maciejewski B, Withers HR, Taylor JM. Incidence and kinetics of distant metastases in patients with operable breast cancer. Neoplasma. 1997;44:3–11.

    PubMed  CAS  Google Scholar 

  29. Goetz MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW, et al. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol. 2005;23:9312–8.

    Article  PubMed  CAS  Google Scholar 

  30. Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee K-H, et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005;97:30–9.

    PubMed  CAS  Google Scholar 

  31. Goetz MP, Knox SK, Suman VJ, Rae JM, Safgren SL, Ames MM, et al. The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat. 2007;101:113–21.

    Article  PubMed  CAS  Google Scholar 

  32. Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thürlimann B, Senn HJ, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol. 2007;18:1133–44 (Erratum in: Ann Oncol. 2007;18:1917).

    Google Scholar 

  33. Melisko M, Lin A, Rugo H. Adjuvant therapy for early stage breast cancer (EBC): distant disease-free survival (DDFS) as a predictor of overall survival (OS). J Clin Oncol. 2007;25(18S):23s (Abstract 583).

    Google Scholar 

  34. Baum M, Buzdar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002;359:2131–9 (Erratum in: Lancet. 2002;360:1520).

    Article  PubMed  CAS  Google Scholar 

  35. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005;365:60–2.

    Article  PubMed  CAS  Google Scholar 

  36. Howell A, On Behalf of the ATAC Trialists’ Group. ATAC (‘Arimidex’, Tamoxifen, Alone or in Combination) completed treatment analysis: anastrozole demonstrates superior efficacy and tolerability compared with tamoxifen. Breast Cancer Res Treat. 2004;Suppl 1, Abstract 1.

  37. Houghton J, On Behalf of the ATAC Trialists’ Group. Initial adjuvant therapy with anastrozole (S) reduced rates of early breast cancer recurrent and adverse events compared with tamoxifen (T)-data reported on behalf of the ATAC (‘Arimidex’, Tamoxifen, Alone or in Combination) Trialists’ group. Ann Oncol. 2006;17(Suppl 9):ix94 (Abstract 243PD).

    Google Scholar 

  38. Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008;9:45–53.

    Article  PubMed  CAS  Google Scholar 

  39. Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353:2747–57.

    Article  PubMed  Google Scholar 

  40. Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1–98. J Clin Oncol. 2007;25:486–92.

    Article  PubMed  CAS  Google Scholar 

  41. Mauriac L, Keshaviah A, Debled M, Mouridsen H, Forbes JF, Thürlimann B, et al. Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1–98 trial. Ann Oncol. 2007;18:859–67.

    Article  PubMed  CAS  Google Scholar 

  42. Boccardo F, Rubagotti A, Puntoni M, Guglielmini P, Amoroso D, Fini A, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole trial. J Clin Oncol. 2005;23:5138–47.

    Article  PubMed  CAS  Google Scholar 

  43. Jakesz R, Gnant M, Greil R, Tausch C, Samonigg H, Kwasny W, et al. The benefits of sequencing adjuvant tamoxifen and anastrozole in postmenopausal women with hormone-responsive early breast cancer: 5 year-analysis of ABCSG Trial 8. Breast Cancer Res Treat. 2005;94(Suppl 1):S10 (Abstract 13).

    Google Scholar 

  44. Jonat W, Gnant M, Boccardo F, Kaufmann M, Rubagotti A, Zuna I, et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta analysis. Lancet Oncol. 2006;7:991–6 (Erratum in: Lancet Oncol. 2007;8:6).

    Article  PubMed  CAS  Google Scholar 

  45. Monnier A. Refining the postmenopausal breast cancer treatment paradigm: the FACE trial. Expert Rev Anticancer Ther. 2006;6:1355–9.

    Article  PubMed  Google Scholar 

  46. Gligorov J, Azria D, Pivot X, Penault-Llorca F, Spielmann M, Namer M. Clinical impact of upfront adjuvant AI therapy on the early risk of recurrence. Eur J Cancer. 2007;Suppl 5:209 (Abstract 2.089).

    Google Scholar 

  47. Dixon JM, Renshaw L, Young O, Murray J, Macaskill EJ, McHugh M, et al. Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer. J Clin Oncol. 2008;26:1671–6.

    Article  PubMed  CAS  Google Scholar 

  48. Gershanovich M, Chaudri H, Campos D. Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Ann Oncol. 1998;9:639–45.

    Article  PubMed  CAS  Google Scholar 

  49. Rugo H, Kaura S, Dranitsaris G. The number needed to treat (NNT) as a measure of drug efficacy: the case of aromatase inhibitors (AIs) in post menopausal women with early breast cancer. St. Gallen Conference 2007. Breast. 2007;16(Suppl 1):S61 (Abstract P170).

    Article  Google Scholar 

  50. Rugo HS, Rourke M, Dranitsaris G, Kaura S. Letrozole or anastrozole in the prevention of early recurrences in postmenopausal women with early stage breast cancer: using number needed to treat (NNT) to compare benefit. European Breast Cancer Conference, Berlin, Germany; 2008, Abstract 236.

  51. Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol. 2005;23:619–29.

    Google Scholar 

  52. Cuzick J, Wale C, On Behalf of the ATAC Trialists’ Group. A detailed analysis of the benefits of anastrozole over tamoxifen for venous thromboembolic events (VTEs) after 5 years treatment. Breast Cancer Res Treat. 2006;100(Suppl 1):S24 (Abstract 104).

    Google Scholar 

  53. Duffy S, On Behalf of the ATAC Trialists’ Group. Anastrozole is associated with a lower risk of endometrial abnormalities than tamoxifen: first report of the ATAC trial endometrial sub-protocol at 6 years follow-up. Breast Cancer Res Treat. 2006;100(Suppl 1):S190 (Abstract 4055).

    Google Scholar 

  54. Bundred NJ, Campbell ID, Davidson N, DeBoer RH, Eidtmann H, Monnier A, et al. Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results. Cancer. 2008;112:1001–10.

    Article  PubMed  CAS  Google Scholar 

  55. Brufsky A, Harker WG, Beck JT, Carroll R, Tan-Chiu E, Seidler C, et al. Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol. 2007;25:829–36.

    Article  PubMed  CAS  Google Scholar 

  56. Chien AJ, Goss PE. Aromatase inhibitors and bone health in women with breast cancer. J Clin Oncol. 2006;24:5305–12.

    Article  PubMed  CAS  Google Scholar 

  57. The Arimidex, Tamoxifen, Alone or in Combination Trialists’ Group, Buzdar A, Howell A, Cuzick J, Wale C, Distler W, et al. Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol. 2006;7:633–43.

    Article  PubMed  CAS  Google Scholar 

  58. Mouridsen H, Keshaviah A, Coates AS, Rabaglio M, Castiglione-Gertsch M, Sun Z, et al. Cardiovascular adverse events during adjuvant endocrine therapy for early breast cancer using LET or tamoxifen: safety analysis of BIG 1–98 trial. J Clin Oncol. 2007;25:5715–22.

    Article  PubMed  CAS  Google Scholar 

  59. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, et al. Randomised trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Nat Cancer Inst. 2005;97:1262–71.

    Article  PubMed  CAS  Google Scholar 

  60. Sourander L, Rajala T, Raiha I, Makinen J, Erkkola R, Helenius H. Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy (ERT). Lancet. 1998;352:1965–9.

    Article  PubMed  CAS  Google Scholar 

  61. Hori Y, Akizuki M, Nishimura R. Comparison of adverse effects on lipid metabolism of Anastrozole with Tamoxifen in adjuvant setting for postmenopausal women with early breast cancer. Eur J Cancer. 2006;Suppl 4:94 (Abstract 172).

    Google Scholar 

  62. Hozumi Y, Aihara T, Takatsuka Y, Osumi S, Aogi K, Imoto S, et al. Chronological changes of side effect profile of anastrozole compared with tamoxifen in Japanese women: findings from N-SAS BC03 trial every 3 months after one year of the randomization. Breast Cancer Res Treat. 2007;106(Suppl 1):S145–6 (Abstract 3059).

    Google Scholar 

  63. Sagara Y, Rai Y. Bone health and anastrozole adverse events in Japan. Breast Cancer Res Treat. 2007;106(Suppl 1):S113 (Abstract 2085).

    Google Scholar 

  64. Moy B, Tu D, Pater JL, Ingle JN, Shepherd LE, Whelan TJ, et al. Clinical outcomes of ethnic minority women in MA.17: a trial of letrozole after 5 years of tamoxifen in postmenopausal women with early stage breast cancer. Ann Oncol. 2006;17:1637–43.

    Article  PubMed  CAS  Google Scholar 

  65. Moy B, Elliott CR, Chapman J-AW, Pater JL, Ding Z, Goss PE. NCIC CTG MA.27: menopausal symptoms of ethnic minority women. Breast Cancer Res Treat. 2006;100(Suppl 1):S144 (Abstract 3059).

    Google Scholar 

  66. Houghton J, On behalf of the ATAC Trialists’ Group. Using anastrozole as initial adjuvant treatment prevents early recurrences and reduces adverse events: updated data from the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial. J Clin Oncol. 2005;23(16S):24s (Abstract 582).

    Google Scholar 

  67. Mouridsen HT, Giobbie-Hurder A, Mauriac L, Paridaens R, Colleorni M, Thuerlimann B, et al. BIG 1–98: a randomized double-blind phase III study evaluating letrozole and tamoxifen given in sequence as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer. Program and Abstracts of the 31st Annual San Antonio Breast Cancer Symposium, December 10–14, San Antonio, Texas; 2008, Abstract 13.

  68. Jones SE, Seynaeve C, Hasenburg A, Rae D, Vannetzel J-M, Paridaens R, et al. Results of the first planned analysis of the TEAM (tamoxifen exemestane adjuvant multinational) prospective randomized phase III trial in hormone sensitive postmenopausal early breast cancer. Program and Abstracts of the 31st Annual San Antonio Breast Cancer Symposium, December 10–14, 2008, San Antonio, Texas; 2008, Abstract 15.

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  1. Department of Surgery and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Masakazu Toi, Hiroyasu Yamashiro & Wakako Tsuji

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Toi, M., Yamashiro, H. & Tsuji, W. Risk reduction of distant metastasis in hormone-sensitive postmenopausal breast cancer. Breast Cancer 16, 207–218 (2009). https://doi.org/10.1007/s12282-009-0096-x

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