Principles of Breast Cancer Therapy

  • Allison W. Kurian
  • Robert W. Carlson


The treatment of breast cancer is largely determined by stage at diagnosis, hormone receptor status, HER-2/neu level of expression or amplification, patient preference, and comorbidity. Available treatments may be divided into those addressing local–regional disease and those primarily addressing systemic disease. Early breast cancer, generally stages 0, I, II, and III, is treated with curative intent, while metastatic or recurrent breast cancer is generally treated with palliative intent. The treatment of most breast cancers is multidisciplinary, incorporating surgery, radiation therapy, and systemic therapy. In this chapter, we review the prognostic and predictive factors for breast cancer, the treatment of early-stage breast cancer, and the treatment of metastatic disease.


Breast Cancer Metastatic Breast Cancer Sentinel Lymph Node Biopsy Zoledronic Acid Ipsilateral Breast Tumor Recurrence 
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.


  1. Baum M et al (2002) 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 359(9324):2131–2139CrossRefPubMedGoogle Scholar
  2. Berry DA et al (2006) Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295(14):1658–1667CrossRefPubMedGoogle Scholar
  3. Boccardo F et al (2006) Switching to anastrozole versus continued tamoxifen treatment of early breast cancer. Updated results of the Italian tamoxifen anastrozole (ITA) trial. Ann Oncol 17(Suppl 7):vii10–vii14CrossRefPubMedGoogle Scholar
  4. Burstein HJ et al (2006) Inadvertent use of aromatase inhibitors in patients with breast cancer with residual ovarian function: cases and lessons. Clin Breast Cancer 7(2):158–161CrossRefPubMedGoogle Scholar
  5. Buzdar AU et al (1998) Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Arimidex Study Group. Cancer 83(6):1142–1152CrossRefPubMedGoogle Scholar
  6. Carey LA et al (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334CrossRefPubMedGoogle Scholar
  7. Carlson RW et al (2007) Invasive breast cancer. J Natl Compr Canc Netw 5(3):246–312PubMedGoogle Scholar
  8. Carrick S et al (2005) Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev 2:CD003372PubMedGoogle Scholar
  9. Chagpar A et al (2003) Outcome of treatment for breast cancer patients with chest wall recurrence according to initial stage: implications for post-mastectomy radiation therapy. Int J Radiat Oncol Biol Phys 57(1):128–135PubMedGoogle Scholar
  10. Chia SK et al (2007) The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer 110(5):973–979CrossRefPubMedGoogle Scholar
  11. Chung CT, Carlson RW (2003) Goals and objectives in the management of metastatic breast cancer. Oncologist 8(6):514–520CrossRefPubMedGoogle Scholar
  12. Citron ML et al (2003) Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21(8):1431–1439Google Scholar
  13. Coleman RE (2002) Efficacy of zoledronic acid and pamidronate in breast cancer patients: a comparative analysis of randomized phase III trials. Am J Clin Oncol 25(6 Suppl 1):S25–S31CrossRefPubMedGoogle Scholar
  14. Contesso G et al (1987) The importance of histologic grade in long-term prognosis of breast cancer: a study of 1,010 patients, uniformly treated at the Institut Gustave-Roussy. J Clin Oncol 5(9):1378–1386PubMedGoogle Scholar
  15. Coombes RC et al (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350(11):1081–1092CrossRefPubMedGoogle Scholar
  16. Coombes RC 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(9561):559–570CrossRefPubMedGoogle Scholar
  17. Davidson NE et al (2005) Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188. J Clin Oncol 23(25):5973–5982CrossRefPubMedGoogle Scholar
  18. Disa JJ, McCarthy CM (2005) Breast reconstruction: a comparison of autogenous and prosthetic techniques. Adv Surg 39:97–119CrossRefPubMedGoogle Scholar
  19. Dressler LG et al (2005) Comparison of HER2 status by fluorescence in situ hybridization and immunohistochemistry to predict benefit from dose escalation of adjuvant doxorubicin-based therapy in node-positive breast cancer patients. J Clin Oncol 23(19):4287–4297CrossRefPubMedGoogle Scholar
  20. 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(9472):1687–1717CrossRefGoogle Scholar
  21. Early Breast Cancer Trialists' Collaborative Group (2000) Ovarian ablation for early breast cancer. Cochrane Database Syst Rev (2):CD000485Google Scholar
  22. Early Breast Cancer Trialists' Collaborative Group (1995) Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. N Engl J Med 333(22):1444–1455CrossRefGoogle Scholar
  23. Fan C et al (2006) Concordance among gene-expression-based predictors for breast cancer. N Engl J Med 355(6):560–569CrossRefPubMedGoogle Scholar
  24. Farquhar C et al (2005) High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer. Cochrane Database Syst Rev (3):CD003139Google Scholar
  25. Fisher B et al (1994) Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 86(7):527–537CrossRefPubMedGoogle Scholar
  26. Fisher B et al (1983) Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer 52(9):1551–1557CrossRefPubMedGoogle Scholar
  27. Fisher B et al (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347(16):1233–1241CrossRefPubMedGoogle Scholar
  28. Fisher ER et al (2001) Fifteen-year prognostic discriminants for invasive breast carcinoma: National Surgical Adjuvant Breast and Bowel Project Protocol-06. Cancer 91(8 Suppl):1679–1687CrossRefPubMedGoogle Scholar
  29. Gelmon K, Chan A, Harbeck N (2006) The role of capecitabine in first-line treatment for patients with metastatic breast cancer. Oncologist 11(Suppl 1):42–51CrossRefPubMedGoogle Scholar
  30. Geyer CE et al (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355(26):2733–2743CrossRefPubMedGoogle Scholar
  31. Goss PE et al (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 97(17):1262–1271CrossRefPubMedGoogle Scholar
  32. Goyal A et al (2006) Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer – results of the ALMANAC validation phase. Breast Cancer Res Treat 99(2):203–208CrossRefPubMedGoogle Scholar
  33. Gradishar W, Chia S, Piccart M (2006) Fulvestrant versus exemestane following prior non-steroidal aromatase inhibitor therapy: first results from EFECT, a randomized, phase III trial in postmenopausal women with advanced breast cancer. In: San Antonio Breast Cancer Symposium. San Antonio, TXGoogle Scholar
  34. Henderson IC et al (2003) Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 21(6):976–983CrossRefPubMedGoogle Scholar
  35. Henson DE et al (1991) Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index. Cancer 68(10):2142–2149CrossRefPubMedGoogle Scholar
  36. Holland DW, Boucher LD, Mortimer JE (2001) Tubular breast cancer experience at Washington University: a review of the literature. Clin Breast Cancer 2(3):210–214CrossRefPubMedGoogle Scholar
  37. Jakesz R 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(9484):455–462CrossRefPubMedGoogle Scholar
  38. Joensuu H et al (2006) Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 354(8):809–820CrossRefPubMedGoogle Scholar
  39. Jones SE et al (2006) Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24(34):5381–5387CrossRefPubMedGoogle Scholar
  40. Jones SE et al (2005) Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol 23(24):5542–5551CrossRefPubMedGoogle Scholar
  41. Kamby C et al (1988) Histological grade and steroid receptor content of primary breast cancer – impact on prognosis and possible modes of action. Br J Cancer 58(4):480–486PubMedGoogle Scholar
  42. Kaufmann M et al (2003) Survival analyses from the ZEBRA study. goserelin (Zoladex) versus CMF in premenopausal women with node-positive breast cancer. Eur J Cancer 39(12):1711–1717CrossRefPubMedGoogle Scholar
  43. Lemanski C et al (2006) Intraoperative radiotherapy given as a boost for early breast cancer: long-term clinical and cosmetic results. Int J Radiat Oncol Biol Phys 64(5):1410–1415PubMedGoogle Scholar
  44. Mamounas EP et al (2005) Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol 23(16):3686–3696CrossRefPubMedGoogle Scholar
  45. Martin M et al (2005) Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 352(22):2302–2313CrossRefPubMedGoogle Scholar
  46. Martin M et al (2006) Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Ann Oncol 17(8):1205–1212CrossRefPubMedGoogle Scholar
  47. Miller K et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357(26):2666–2676CrossRefPubMedGoogle Scholar
  48. Miller KD et al (2005) Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23(4):792–799CrossRefPubMedGoogle Scholar
  49. Muss HB et al (1991) Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association. N Engl J Med 325(19):1342–1348CrossRefPubMedGoogle Scholar
  50. Olivotto IA et al (2005) Population-based validation of the prognostic model ADJUVANT! for early breast cancer. J Clin Oncol 23(12):2716–2725CrossRefPubMedGoogle Scholar
  51. O‘Shaughnessy J et al (2002) Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 20(12):2812–2823CrossRefPubMedGoogle Scholar
  52. Ott OJ et al (2007) Accelerated partial breast irradiation with multi-catheter brachytherapy: Local control, side effects and cosmetic outcome for 274 patients. Results of the German-Austrian multi-centre trial. Radiother Oncol 82(3):281–286CrossRefPubMedGoogle Scholar
  53. Paik S et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826CrossRefPubMedGoogle Scholar
  54. Piccart MJ et al (2001) Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol 19(12):3103–3110PubMedGoogle Scholar
  55. Piccart-Gebhart MJ et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672CrossRefPubMedGoogle Scholar
  56. Pritchard KI et al., (2006) HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med 354(20):2103–2111CrossRefPubMedGoogle Scholar
  57. Ragaz J 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(2):116–126CrossRefPubMedGoogle Scholar
  58. Ravdin PM et al (2001) Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 19(4):980–991PubMedGoogle Scholar
  59. Recht A et al (2001) Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19(5):1539–1569PubMedGoogle Scholar
  60. Riou G et al., (2001) c-erbB-2 (HER-2/neu) gene amplification is a better indicator of poor prognosis than protein over-expression in operable breast-cancer patients. Int J Cancer 95(4):266–270CrossRefPubMedGoogle Scholar
  61. Robertson JF et al (2003) Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer 98(2):229–238CrossRefPubMedGoogle Scholar
  62. Romond EH et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684CrossRefPubMedGoogle Scholar
  63. Rosenberg J, Chia YL, Plevritis S (2005) The effect of age, race, tumor size, tumor grade, and disease stage on invasive ductal breast cancer survival in the U.S. SEER database. Breast Cancer Res Treat 89(1):47–54CrossRefPubMedGoogle Scholar
  64. Rosselli Del Turco M et al (1994) Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. National Research Council Project on Breast Cancer follow-up. JAMA 271(20):1593–1597CrossRefPubMedGoogle Scholar
  65. Shan K, Lincoff AM, Young JB (1996) Anthracycline-induced cardiotoxicity. Ann Intern Med 125(1):47–58PubMedGoogle Scholar
  66. Simon R, Norton L (2006) The Norton-Simon hypothesis: designing more effective and less toxic chemotherapeutic regimens. Nat Clin Pract Oncol 3(8):406–407CrossRefPubMedGoogle Scholar
  67. Singletary SE, Connolly JL (2006) Breast cancer staging: working with the sixth edition of the AJCC cancer staging manual. CA Cancer J Clin 56:37–47CrossRefPubMedGoogle Scholar
  68. Singletary SE et al (2002) Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 20(17):3628–3636CrossRefPubMedGoogle Scholar
  69. Slamon D et al (2001) Phase lll randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel with doxorubicin and Slamon, D.J., et al., Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792CrossRefPubMedGoogle Scholar
  70. Sorlie T et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874CrossRefPubMedGoogle Scholar
  71. Stolier AJ, Corsetti RL (2005) Newly diagnosed breast cancer patients choose bilateral mastectomy over breast-conserving surgery when testing positive for a BRCA1/2 mutation. Am Surg 71(12):1031–1033PubMedGoogle Scholar
  72. Talman ML, Jensen MB, Rank F (2007) Invasive lobular breast cancer. Prognostic significance of histological malignancy grading. Acta Oncol 46(6):803–809CrossRefPubMedGoogle Scholar
  73. Tan-Chiu E et al (2005) Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol 23(31):7811–7819CrossRefPubMedGoogle Scholar
  74. Tanner M et al (2006) Topoisomerase IIalpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401. J Clin Oncol 24(16):2428–2436CrossRefPubMedGoogle Scholar
  75. Taylor CW et al (1998) Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol 16(3):994–999PubMedGoogle Scholar
  76. Telli ML et al (2007) Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol 25(23):3525–3533CrossRefPubMedGoogle Scholar
  77. Thurlimann B et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353(26):2747–2757CrossRefPubMedGoogle Scholar
  78. Thurlimann B et al (2003) Efficacy of tamoxifen following anastrozole (‘Arimidex') compared with anastrozole following tamoxifen as first-line treatment for advanced breast cancer in postmenopausal women. Eur J Cancer 39(16):2310–2317CrossRefPubMedGoogle Scholar
  79. Slamon D et al (2005) Phase lll randomized trial compaing doxorubicin and cyclophosphamide followed by docetaxel with doxorubicin and trastuzumab with docetaxel, carboplatin and trastuzumab in HER2 positive early breast cancer patients: BCIRG 006 study, in San Antonio Breast Cancer Symposium. San Antonio, TX, Abstract #1Google Scholar
  80. van de Vijver MJ et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347(25):1999–2009CrossRefPubMedGoogle Scholar
  81. Venturini M et al (2005) Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial. J Natl Cancer Inst 97(23):1724–1733CrossRefPubMedGoogle Scholar
  82. Veronesi U et al (2003) A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 349(6):546–553CrossRefPubMedGoogle Scholar
  83. Veronesi U 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(16):1227–1232CrossRefPubMedGoogle Scholar
  84. Vo T et al (2007) Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy. Am J Surg 194(4):527–531CrossRefPubMedGoogle Scholar
  85. Wilkinson GS et al (2007) Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis. J Natl Cancer Inst 99(13):1016–1024CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Division of Oncology, Department of Medicine; Department of Health Research and PolicyStanford University School of MedicineStanfordUSA

Personalised recommendations