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Improving decision-making in early breast cancer: who to treat and how?

  • Optimizing Breast Cancer Patient
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Abstract

Recent advances in primary and adjuvant treatment for early-stage breast cancer have reduced mortality rates, and improved the overall prognosis. Many patients can be cured, while others may survive for 10 years or more beyond diagnosis, thanks to a combination of preoperative therapy, surgery, radiotherapy, and systemic adjuvant therapy. Minimally invasive procedures, more effective drugs, and improved treatment regimens are helping to reduce breast cancer recurrences and deaths, while minimizing side effects and maintaining quality of life. Despite such improvements, a significant number of patients with early disease will relapse, including those who are clinically disease-free after primary and adjuvant therapy. Advances in breast tumor biology have led to the discovery of many different tumor types, and a uniform approach to treatment is no longer appropriate. Potential markers have been identified for the risk of relapse and responsiveness to a given therapy, thus treatment decisions and clinical guidelines, previously based on data from large patient populations, are changing to reflect a movement towards individually tailored treatment. Refinements in clinical practice will help physicians to identify the patients who will benefit the most from a particular approach, reducing overtreatment, and sparing patients unnecessary therapy. Genetic studies are helping to increase our understanding of the metastatic potential of tumors, leading to the development of adjuvant therapies for the prevention of metastases in selected patients. This article reviews the latest advances in treatment for early breast cancer, and explores how research and clinical practice are evolving to improve therapies and treatment decision-making, allowing physicians to optimize patient care.

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References

  1. Goldhirsch A, Wood WC, Gelber RD et al (2007) Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol 18:1133–1144. doi:10.1093/annonc/mdm271

    Article  PubMed  CAS  Google Scholar 

  2. Arriagada R, Rutqvist LE, Johansson H et al (2008) Predicting distant dissemination in patients with early breast cancer. Acta Oncol 3:1–9. doi:10.1080/02841860701829661

    Google Scholar 

  3. Rakha EA, El-Sayed ME, Lee AH et al (2008) Prognostic significance of Nottingham histological grade in invasive breast carcinoma. J Clin Oncol 26:3153–3158. doi:10.1200/JCO.2007.15.5986

    Article  PubMed  Google Scholar 

  4. Sotiriou C, Wirapati P, Loi S et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98:262–272

    PubMed  CAS  Google Scholar 

  5. Lee AH, Ellis IO (2008) The nottingham prognostic index for invasive carcinoma of the breast. Pathol Oncol Res 14:113–115

    Article  PubMed  Google Scholar 

  6. Early Breast Cancer Trialists’ Collaborative Group (1992) 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 339:71–85

    Google Scholar 

  7. Lønning PE, Knappskog S, Staalesen V et al (2007) Breast cancer prognostication and prediction in the postgenomic era. Ann Oncol 18:1293–1306. doi:10.1093/annonc/mdm013

    Article  PubMed  Google Scholar 

  8. van’t Veer LJ, Dai H, van de Vijver MJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536. doi:10.1038/415530a

    Article  CAS  Google Scholar 

  9. Wang Y, Klijn JGM, Zhang Y et al (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365:671–679

    PubMed  CAS  Google Scholar 

  10. Minn AJ, Kang Y, Serganova I et al (2005) Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest 115:44–55

    PubMed  CAS  Google Scholar 

  11. Smid M, Wang Y, Klijn JG et al (2006) Genes associated with breast cancer metastatic to bone. J Clin Oncol 24:2261–2267. doi:10.1200/JCO.2005.03.8802

    Article  PubMed  CAS  Google Scholar 

  12. Dhakal HP, Naume B, Synnestvedt M et al (2008) Vascularization in primary breast carcinomas: its prognostic significance and relationship with tumor cell dissemination. Clin Cancer Res 14:2341–2350

    Article  PubMed  CAS  Google Scholar 

  13. Sohn VY, Arthurs ZM, Sebesta JA et al (2008) Primary tumor location impacts breast cancer survival. Am J Surg 195:641–644. doi:10.1016/j.amjsurg.2007.12.039

    Article  PubMed  Google Scholar 

  14. Annecke K, Schmitt M, Euler U et al (2008) uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial. Adv Clin Chem 45:31–45. doi:10.1016/S0065-2423(07)00002-9

    Article  PubMed  CAS  Google Scholar 

  15. Kumar AS, Bhatia V, Henderson IC (2005) Overdiagnosis and overtreatment of breast cancer: rates of ductal carcinoma in situ: a US perspective. Breast Cancer Res Treat 7:274–275

    Google Scholar 

  16. Jones JL (2006) Overdiagnosis and overtreatment of breast cancer: progression of ductal carcinoma in situ: the pathological perspective. Breast Cancer Res 8:204. doi:10.1186/bcr1397

    Article  PubMed  Google Scholar 

  17. Lønning PE, Sorlie T, Borresen-Dale AL (2005) Genomics in breast cancer-therapeutic implications. Nat Clin Pract Oncol 2:26–33. doi:10.1038/ncponc0072

    Article  PubMed  CAS  Google Scholar 

  18. Goldhirsch A, Glick JH, Gelber RD et al (2005) Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 16:1569–1583. doi:10.1093/annonc/mdi326

    Article  PubMed  CAS  Google Scholar 

  19. Arriola E, Rodriguez-Pinnilla SM, Lambros MB et al (2007) Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer. Breast Cancer Res Treat 106:181–189. doi:10.1007/s10549-006-9492-5

    Article  PubMed  CAS  Google Scholar 

  20. Cheang MC, van de Rijm M, Nielsen TO (2008) Gene expression profiling of breast cancer. Annu Rev Pathol 3:67–97. doi:10.1146/annurev.pathmechdis.3.121806.151505

    Article  PubMed  CAS  Google Scholar 

  21. Kaufmann M, Hortobagyi GN, Goldhirsch A et al (2006) Recommendations from an international expert panel on use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 24:1940–1949. doi:10.1200/JCO.2005.02.6187

    Article  PubMed  Google Scholar 

  22. Fisher B, Brown A, Mamounas E et al (1997) Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 15:2483–2493

    PubMed  CAS  Google Scholar 

  23. Fisher B, Bryant J, Wolmark N et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685

    PubMed  CAS  Google Scholar 

  24. Bonadonna G, Valagussa P, Brambilla C et al (1998) Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol 16:93–100

    PubMed  CAS  Google Scholar 

  25. Buzdar AU, Valerom R, Theriault RL et al (2003) Pathological complete response to chemotherapy is related to hormone receptor status. Breast Cancer Res Treat 83:569a (Abstract 302)

    Google Scholar 

  26. Gianni L, Baselga J, Eiermann W et al (2005) European Cooperative Trial in Operable Breast Cancer (ECTO): improved freedom from progression (FFP) from adding paclitaxel (T) to doxorubicin (A) followed by cyclophosphamide methotrexate and fluorouracil (CMF). Proc Am Soc Clin Oncol 23:7s (Abstract 513)

    Google Scholar 

  27. Bear HD, Anderson S, Smith RE et al (2006) Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 24:2019–2027. doi:10.1200/JCO.2005.04.1665

    Article  PubMed  CAS  Google Scholar 

  28. Eiermann W, Paepke S, Appfelstaedt J et al (2001) Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol 12:1527–1532. doi:10.1023/A:1013128213451

    Article  PubMed  CAS  Google Scholar 

  29. Smith IE, Dowsett M, Ebbs SR et al (2005) Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol 23:5108–5116. doi:10.1200/JCO.2005.04.005

    Article  PubMed  CAS  Google Scholar 

  30. Semiglazov VF, Semiglazov V, Ivanov V et al (2004) The relative efficacy of neoadjuvant endocrine therapy vs chemotherapy in postmenopausal women with ER-positive breast cancer. Proc Am Soc Clin Oncol 22:517 (Abstract 519)

    Google Scholar 

  31. Semiglazov V, Kletsel A, Semiglazov V et al (2005) Exemestane vs tamoxifen as neoadjuvant endocrine therapy for postmenopausal women with ER+ breast cancer (T2N1–2, T3N0–1, T4N0M0). Proc Am Soc Clin Oncol 23:11s (Abstract 530)

    Google Scholar 

  32. Pestalozzi BC, Luporsi-Gely E, Jost LM et al (2005) ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of primary breast cancer. Ann Oncol 16(suppl 1):i7–i9. doi:10.1093/annonc/mdi825

    Article  PubMed  Google Scholar 

  33. Veronesi U, Cascinelli N, Mariani L et al (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227–1232. doi:10.1056/NEJMoa020989

    Article  PubMed  Google Scholar 

  34. Smith IE, Ross GM (2004) Breast radiotherapy after lumpectomy—no longer always necessary. N Engl J Med 351:1021–1023. doi:10.1056/NEJMe048173

    Article  PubMed  CAS  Google Scholar 

  35. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366:2087–2106

    Google Scholar 

  36. Fisher B, Anderson S, Redmond CK et al (1995) Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 333:1456–1461. doi:10.1056/NEJM199511303332203

    Article  PubMed  CAS  Google Scholar 

  37. Fyles AW, McCready DR, Manchul LA et al (2004) Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med 351:963–970. doi:10.1056/NEJMoa040595

    Article  PubMed  CAS  Google Scholar 

  38. Hughes KS, Schnaper LA, Berry D et al (2004) Radiation Therapy Oncology Group; Eastern Cooperative Oncology Group. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 351:971–977. doi:10.1056/NEJMoa040587

    Article  PubMed  CAS  Google Scholar 

  39. Veronesi U, Marubini E, Mariani L et al (2001) Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol 12:997–1003. doi:10.1023/A:1011136326943

    Article  PubMed  CAS  Google Scholar 

  40. Ragaz J, Olivotto IA, Spinelli JJ et al (2005) Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 97:116–126

    Article  PubMed  Google Scholar 

  41. Veronesi U, Gatti G, Luini A et al (2003) Intraoperative radiation therapy for breast cancer: technical notes. Breast J 9:106–112. doi:10.1046/j.1524-4741.2003.09208.x

    Article  PubMed  Google Scholar 

  42. Patel RR, Das RK (2006) Image-guided breast brachytherapy: an alternative to whole-breast radiotherapy. Lancet 7:407–415. doi:10.1016/S1470-2045(06)70692-1

    Article  Google Scholar 

  43. Biganzoli L, Claudino WM, Pestri M et al (2007) Selection of chemotherapeutic drugs in adjuvant programs based on molecular profiles: where do we stand? Crit Rev Oncol Hematol 62:1–8. doi:10.1016/j.critrevonc.2006.10.004

    Article  PubMed  Google Scholar 

  44. Berry DA, Cirrincione C, Henderson IC et al (2006) Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295:1658–1667. doi:10.1001/jama.295.14.1658

    Article  PubMed  CAS  Google Scholar 

  45. Colozza M, De Azambuja E, Cardoso F et al (2006) Breast cancer: achievements in adjuvant systemic therapies in the pre-genomic era. Oncologist 11:111–125. doi:10.1634/theoncologist.11-2-111

    Article  PubMed  CAS  Google Scholar 

  46. Goldhirsch A, Coates A, Gelber R, St Gallen Expert Panel Members et al (2006) First—select the target: better choice of adjuvant treatments for breast cancer patients. Ann Oncol 17:1772–1776. doi:10.1093/annonc/mdl398

    Article  PubMed  CAS  Google Scholar 

  47. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (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. doi:10.1016/S0140-6736(05)66544-0

    Article  CAS  Google Scholar 

  48. Albain K, Barlow W, O’Malley F et al (2004) Mature outcomes and new biologic correlates on phase III intergroup trial 0100 (INT-0100, SWOG-8814): concurrent (CAFT) vs sequential (CAF-T) chemohormonal therapy (cyclophosphamide, doxorubicin, 5-fluorouracil, tamoxifen) vs. T alone for postmenopausal, node-positive, estrogen (ER) and/or progesterone PgR receptor-positive breast cancer. Breast Cancer Res Treat 84:132 (Abstract 37)

    Google Scholar 

  49. Albain KS (2005) Do all patients with endocrine-responsive early breast cancer need adjuvant chemotherapy before endocrine treatment? Breast 14:S9–S10. doi:10.1016/S0960-9776(05)80026-8

    Article  Google Scholar 

  50. Andre F, Broglio K, Roche H et al (2007) Estrogen receptor expression and efficacy of docetaxel in early breast cancer: a pooled analysis of 3,490 patients included in two randomized trials. J Clin Oncol 25:12 S (Abstract 537)

    Article  CAS  Google Scholar 

  51. Muss HB, Biganzoli L, Sargent DJ, Aapro M (2007) Adjuvant therapy in the elderly: making the right decision. J Clin Oncol 25:1870–1875. doi:10.1200/JCO.2006.10.3457

    Article  PubMed  Google Scholar 

  52. Paik S, Tang G, Shak S et al (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24:3726–3734. doi:10.1200/JCO.2005.04.7985

    Article  PubMed  CAS  Google Scholar 

  53. Juenger J, Schellberg D, Kraemer S et al (2002) Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Heart 87:235–241. doi:10.1136/heart.87.3.235

    Article  PubMed  CAS  Google Scholar 

  54. NCCN Clinical Practical Guidelines in Oncology™ Breast Cancer V.2.2008. Available at http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf Last accessed 06 August 2008

  55. Winer EP, Hudis C, Burstein HJ et al (2005) 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. J Clin Oncol 23:619–629. doi:10.1200/JCO.2005.09.121

    Article  PubMed  CAS  Google Scholar 

  56. Jakesz R, Jonat W, Gnant M et al (2005) Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 366:455–462. doi:10.1016/S0140-6736(05)67059-6

    Article  PubMed  CAS  Google Scholar 

  57. Coombes RC, Kilburn LS, Snowdon CF et al (2007) Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 369:559–570. doi:10.1016/S0140-6736(07)60200-1

    Article  PubMed  CAS  Google Scholar 

  58. Howell A, Cuzick J, Baum M et al (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62. doi:10.1016/S0140-6736(05)74803-0

    Article  PubMed  CAS  Google Scholar 

  59. Coates AS, Keshaviah A, Thürlimann B et al (2007) 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 25:486–492. doi:10.1200/JCO.2006.08.8617

    Article  PubMed  CAS  Google Scholar 

  60. Mauriac L, Keshaviah A, Debled M et al (2007) Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1–98 trial. Ann Oncol 18:859–867. doi:10.1093/annonc/mdm001

    Article  PubMed  CAS  Google Scholar 

  61. Brufsky A, Harker WG, Beck JT et al (2007) Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol 25:829–836

    Article  PubMed  CAS  Google Scholar 

  62. Bundred N, Campbell I, Coleman R et al (2006) Zoledronic acid in the prevention of cancer treatment-induced bone loss in postmenopausal women receiving letrozole as adjuvant therapy for early breast cancer (ZO-FAST study). Eur J Cancer Suppl 4:48 (Abstract 12)

    Article  Google Scholar 

  63. Caraglia M, Santini D, Marra M et al (2006) Emerging anticancer molecular mechanisms of aminobisphosphonates. Endocr Relat Cancer 13:7–26. doi:10.1677/erc.1.01094

    Article  PubMed  CAS  Google Scholar 

  64. Jagdev SP, Coleman RE, Shipman CM, Rostami-H A, Croucher PI (2001) The bisphosphonate, ZA, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer 84:1126–1134. doi:10.1054/bjoc.2001.1727

    Article  PubMed  CAS  Google Scholar 

  65. Neville-Webbe HL, Evans CA, Coleman RE, Holen I (2006) Mechanisms of the synergistic interaction between the bisphosphonate ZA and the chemotherapy agent paclitaxel in breast cancer cells in vitro. Tumour Biol 27:92–103. doi:10.1159/000092489

    Article  PubMed  CAS  Google Scholar 

  66. Hillner BE, Ingle JN, Chlebowski RT et al (2003) American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 21:4042–4057. doi:10.1200/JCO.2003.08.017

    Article  PubMed  CAS  Google Scholar 

  67. Aapro MS, Hadji P, Brufsky A et al (2007) Recommendations for the prevention of aromatase inhibitor-associated bone loss in women with breast cancer. Eur J Cancer Suppl 5:186 (Abstract 2007)

    Article  Google Scholar 

  68. Wolmark N, Wang J, Mamounas E et al (2001) Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. JNCI Monogr 30:96–102

    Google Scholar 

  69. van der Hage JA, van der Velde CJ, Julien JP et al (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 19:4224–4237

    PubMed  Google Scholar 

  70. Mauriac L, MacGrogan G, Avril A et al (1999) Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: a unicentre randomized trial with a 124-month median follow-up. Institut Bergonié Bordeaux Groupe Sein (IBBGS). Ann Oncol 10:47–52. doi:10.1023/A:1008337009350

    Article  PubMed  CAS  Google Scholar 

  71. Scholl SM, Fourquet A, Asselain B et al (1994) Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial: S6. Eur J Cancer 30A:645–652. doi:10.1016/0959-8049(94)90537-1

    Article  PubMed  CAS  Google Scholar 

  72. Broët P, Scholl SM, de la Rochefordière A et al (1999) Short and long-term effects on survival in breast cancer patients treated by primary chemotherapy: an updated analysis of a randomized trial. Breast Cancer Res Treat 58:151–156. doi:10.1023/A:1006339918798

    Article  PubMed  Google Scholar 

  73. Makris A, Powles TJ, Ashley SE et al (1998) A reduction in the requirements for mastectomy in a randomized trial of neoadjuvant chemoendocrine therapy in primary breast cancer. Ann Oncol 9:1179–1184. doi:10.1023/A:1008400706949

    Article  PubMed  CAS  Google Scholar 

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The author of this article has no commercial associations (e.g., consultancies, stock ownership, equity interests, patentlicensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All funding sources supporting the work and all institutional or corporate affiliations of the author are acknowledged.

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  1. Medical Oncology Service, Hospital Universitario Arnau Vilanova, Av. Alcalde Rovira Roure 80, 25198, Lleida, Spain

    Antonio Llombart-Cussac

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Llombart-Cussac, A. Improving decision-making in early breast cancer: who to treat and how?. Breast Cancer Res Treat 112 (Suppl 1), 15–24 (2008). https://doi.org/10.1007/s10549-008-0234-8

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