Archives of Gynecology and Obstetrics

, Volume 288, Issue 6, pp 1203–1212 | Cite as

Breakthroughs in research and treatment of early breast cancer: an overview of the last three decades

  • Manfred Kaufmann
  • Gunter von Minckwitz
  • Jonas Bergh
  • Pier-Franco Conte
  • Sarah Darby
  • Wolfgang Eiermann
  • Antony Howell
  • Marion Kiechle
  • Davide Mauri
  • Hans-Jörg Senn
  • Giuseppe Viale
  • Sibylle Loibl


Breast cancer has become curable for the majority of women in Western Europe and North America. Advances have been made in imaging diagnostics as well as the implementation of nationwide screening programmes. Nowadays, we talk about prevention as well as treatment. Pathology has moved from pure morphology (tumour type, grade and stage) to biological characterisation of the tumour. Treatment has changed considerably through a better understanding of the disease; from a local disease predominated by extensive and mutilating surgical techniques to a point where breast cancer has come into its own as a systemic disease with equal “rights” to local as well as systemic treatment. This paradigm shift has led to a multidisciplinary approach of the understanding and treatment of breast cancer. Molecular classification has changed the understanding of breast cancer and will be the basis for an even more individualised treatment. New (biological) agents will help to further tailor treatment to response or resistance. While systemic treatment has been increased in number and duration surgical/local strategies have been reduced to minimum. Evidence-based medicine has helped to improve and standardise treatment of breast cancer. This review summarises the 10th Biedenkopf meeting that was held to review the advances in breast cancer understanding and treatment.


Breast cancer Prevention Chemotherapy Endocrine therapy Targeted agents Surgery Radiotherapy 



We thank the independent, non-profit BANSS Foundation, Biedenkopf/Lahn, Germany, for financial support, and the GBG Forschungs-GmbH, Neu-Isenberg, Germany for logistical support of the meeting. All members of the panel had input in the discussion and formulation of the article. The symposium as well as the manuscript preparation was conducted independent of the pharmaceutical industry. The report was drafted entirely by the meeting participants without any paid assistance.

Conflict of interest

None of the co-authors has any conflict of interest to declare.


  1. 1.
    Howlader N, Noone AM, Krapcho M et al. (2010) SEER cancer statistics review, 1975–2008. National Cancer Institute. Bethesda.
  2. 2.
    Peto R, Boreham J, Clarke M, Davies C, Beral V (2000) UK and USA breast cancer deaths down 25% in year 2000 at ages 20–69 years. Lancet 355:1822PubMedCrossRefGoogle Scholar
  3. 3.
    Saurel CA, Patel TA, Perez EA (2010) Changes to adjuvant systemic therapy in breast cancer: a decade in review. Changes to adjuvant systemic therapy in breast cancer: a decade in review. Clin Breast Cancer 10:196–208PubMedCrossRefGoogle Scholar
  4. 4.
    NIH Consensus Conference (1991) Treatment of early breast cancer. JAMA 265:391–395CrossRefGoogle Scholar
  5. 5.
    Powles T, 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 352:98–101PubMedGoogle Scholar
  6. 6.
    Cuzick J, Powles T, Veronesi U et al (2003) Overview of the main outcomes in Breast-Cancer Prevention Trials. Lancet 361:296–300PubMedCrossRefGoogle Scholar
  7. 7.
    Cuzick J, Forbes JF, Sestak I et al (2007) Long-term results of tamoxifen prophylaxis for breast cancer-96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 99:272–282PubMedCrossRefGoogle Scholar
  8. 8.
    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. J Natl Cancer Inst 90:1371–1388PubMedCrossRefGoogle Scholar
  9. 9.
    Martino S, Cauley JA, Barrett-Connor E et al (2004) Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 9:1751–1761CrossRefGoogle Scholar
  10. 10.
    Cuzick J, Baum M (1985) Tamoxifen and contralateral breast cancer. Lancet 2:282PubMedCrossRefGoogle Scholar
  11. 11.
    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 355:125–137PubMedCrossRefGoogle Scholar
  12. 12.
    Martino S, Cauley JA, Barrett-Connor E et al (2004) Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 96:1751–1761PubMedCrossRefGoogle Scholar
  13. 13.
    Vogel VG, Costantino JP, Wickerham DL et al (2010) Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res 6:696–706CrossRefGoogle Scholar
  14. 14.
    Baum M, Budzar AU, Cuzick J 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 359:2131–2139PubMedCrossRefGoogle Scholar
  15. 15.
    Goss PE, Ingle JN, Alés-Martínez JE et al (2011) Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 364:2381–2391PubMedCrossRefGoogle Scholar
  16. 16.
    von Minckwitz G, Loibl S, Jackisch C et al (2011) The GISS trial: a phase II prevention trial of screening plus goserelin, ibandronate, versus screening alone in premenopausal women at increased risk of breast cancer. Cancer Epidemiol Biomarkers Prev 20:2141–2149CrossRefGoogle Scholar
  17. 17.
    Howell A, Ashcroft L, Dowsett M et al. (2006) A randomised pilot study of raloxifene and goserelin plus screening versus screening alone in premenopausal women at high risk of breast cancer. Poster presented at the 29th Annual San Antonio Breast Cancer Symposium, San AntonioGoogle Scholar
  18. 18.
    Kauff ND, Satagopan JM, Robson ME et al (2002) Risk-Reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346:1609–1615PubMedCrossRefGoogle Scholar
  19. 19.
    Kurian AW, Sigal BM, Plevritis SK (2010) Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers. J Clin Oncol 28:222–231PubMedCrossRefGoogle Scholar
  20. 20.
    Prentice RL, Caan B, Chlebowski RT et al (2006) Low-fat dietary pattern and risk of invasive breast cancer: the women’s health initiative randomized controlled dietary modification trial. JAMA 295:629–642PubMedCrossRefGoogle Scholar
  21. 21.
    Harvie M, Howell A, Vierkant RA et al (2005) Association of gain and loss of weight before and after menopause with risk of postmenopausal breast cancer in the Iowa women’s health study. Cancer Epidemiol Biomarkers Prev 4:656–661CrossRefGoogle Scholar
  22. 22.
    Friedenreich CM (2011) Physical activity and breast cancer: review of the epidemiologic evidence and biologic mechanisms. Recent Results Cancer Res 188:125–139PubMedCrossRefGoogle Scholar
  23. 23.
    Breast Cancer Linkage Consortium (1997) Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Lancet 349:1505–1510CrossRefGoogle Scholar
  24. 24.
    Armstrong K, Eisen A, Weber B (2000) Assessing the risk of breast cancer. N Engl J Med 342:564–571PubMedCrossRefGoogle Scholar
  25. 25.
    Miki Y, Swensen J, Shattuck-Eidens D et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71PubMedCrossRefGoogle Scholar
  26. 26.
    Meindl A, Hellebrand H, Wiek C et al (2010) Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet 42:410–414PubMedCrossRefGoogle Scholar
  27. 27.
    Loveday C, Turnbull C, Ramsay E et al (2011) Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 43:879–894PubMedCrossRefGoogle Scholar
  28. 28.
    King MC, Marks JH, Mandell JB (2003) New York Breast Cancer Study Group. Breast and ovarian cancer risk due to inherited mutations in BRCA 1 and BRCA 2. Science 302:643–646PubMedCrossRefGoogle Scholar
  29. 29.
    Wurtman R (1968) Estrogen receptor: ambiguities in the use of this term. Science 159:1261PubMedCrossRefGoogle Scholar
  30. 30.
    Cuzick J, Dowsett M, Pineda S et al (2011) Prognostic value of a combined estrogen receptor, progesterone receptor, ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the genomic health recurrence score in early breast cancer. J Clin Oncol 29:4273–4278PubMedCrossRefGoogle Scholar
  31. 31.
    Semba K, Kamata N, Toyoshima K, Yamamoto T (1985) A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci USA 82:6497–6501PubMedCrossRefGoogle Scholar
  32. 32.
    Slamon DJ, Godolphin W, Jones LA et al (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712PubMedCrossRefGoogle Scholar
  33. 33.
    Hammond ME, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2795PubMedCrossRefGoogle Scholar
  34. 34.
    Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145PubMedCrossRefGoogle Scholar
  35. 35.
    Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20PubMedCrossRefGoogle Scholar
  36. 36.
    Dowsett M, Nielsen TO, A’Hern R et al (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst 103:1656–1664PubMedCrossRefGoogle Scholar
  37. 37.
    Perou CM, Sørlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRefGoogle Scholar
  38. 38.
    Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ (2011) Panel members. Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol 22:1736–1747PubMedCrossRefGoogle Scholar
  39. 39.
    Jatoi K, Kaufmann M, Petit JY (2006) Atlas of breast surgery. Springer, BerlinGoogle Scholar
  40. 40.
    Veronesi U, Cascinelli N, Mariani 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 347:1227–1232PubMedCrossRefGoogle Scholar
  41. 41.
    Fisher B, Anderson S, Bryant J 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 347:1233–1241PubMedCrossRefGoogle Scholar
  42. 42.
    Kaufmann M, Morrow M, von Minckwitz G, Harris JR (2010) Biedenkopf expert panel members. Locoregional treatment of primary breast cancer: consensus recommendations from an international expert panel. Cancer 116:1184–1191PubMedCrossRefGoogle Scholar
  43. 43.
    Giuliano AE, Hunt KK, Ballman KV et al (2011) Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 305:569–575PubMedCrossRefGoogle Scholar
  44. 44.
    Darby S, McGale P, Correa C et al (2011) Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378:1707–1716PubMedCrossRefGoogle Scholar
  45. 45.
    Clarke M, Collins R, Darby S et al (2005) Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). 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 366:2087–2106PubMedGoogle Scholar
  46. 46.
    Darby SC, McGale P, Taylor CW, Peto R (2005) Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 3,00,000 women in US SEER cancer registries. Lancet Oncol 6:557–565PubMedCrossRefGoogle Scholar
  47. 47.
    Taylor CW, Povall JM, McGale P et al (2008) Cardiac dose from tangential breast cancer radiotherapy in the year 2006. Int J Radiat Oncol Biol Phys 72:501–507PubMedCrossRefGoogle Scholar
  48. 48.
    Vaidya JS, Joseph DJ, Tobias JS et al (2010) Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 376:91–102PubMedCrossRefGoogle Scholar
  49. 49.
    Schabel FM Jr (1967) Concepts for treatment of micrometastases developed in murine systems. Am J Roentgenol 126:500–511CrossRefGoogle Scholar
  50. 50.
    Goldhirsch A, Glick JH, Gelber RD, Coates A, Senn HJ (2005) Meeting highlights: international St. Gallen expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 16:1569–1583PubMedCrossRefGoogle Scholar
  51. 51.
    Peto R, Davies C, Godwin J et al (2012) Comparison between polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome in 1,00,000 women in 123 randomised trials. Lancet 379:432–444PubMedCrossRefGoogle Scholar
  52. 52.
    Berry DA, Noto TU, Jhonson MM et al (2011) High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials. J Clin Oncol 29:3214–3223PubMedCrossRefGoogle Scholar
  53. 53.
    Citron ML, Berry DA, Cirrincione C 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 21:1431–1439PubMedCrossRefGoogle Scholar
  54. 54.
    Möbus V, Jackisch C, Lueck HJ et al (2010) Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: mature results of an AGO phase III study. J Clin Oncol 28:2874–2880CrossRefGoogle Scholar
  55. 55.
    Bonilla L, Ben-Aharon I, Vidal L, Gafter-Gvili A, Leibovici L, Stemmer SM (2010) Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 102:1845–1854PubMedCrossRefGoogle Scholar
  56. 56.
    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 15:2483–2493PubMedGoogle Scholar
  57. 57.
    Kaufmann M, Hortobagyi GN, Goldhirsch A et al (2006) Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 24:1940–1949PubMedCrossRefGoogle Scholar
  58. 58.
  59. 59.
    von Minckwitz G, Untch M, Blohmer JU et al (2012) Definition and impact of pathological complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796–1804CrossRefGoogle Scholar
  60. 60.
    von Minckwitz G, Untch M, Nüesch E et al (2011) Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat 125:145–156CrossRefGoogle Scholar
  61. 61.
    Liedtke C, Mazouni C, Hess KR et al (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26:1275–1281PubMedCrossRefGoogle Scholar
  62. 62.
    Untch M, Fasching PA, Konecny GE et al (2011) Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol 29:3351–3357PubMedCrossRefGoogle Scholar
  63. 63.
    Untch M, Loibl S, Bischoff J et al (2012) Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 13:135–144PubMedCrossRefGoogle Scholar
  64. 64.
    Gianni L, Pienkowski T, Im YH et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32PubMedCrossRefGoogle Scholar
  65. 65.
    Baselga J, Bradbury I, Eidtmann H et al (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379:633–640PubMedCrossRefGoogle Scholar
  66. 66.
    Guarneri V, Frassoldati A, Bottini A et al (2012) Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol 30:1989–1995PubMedCrossRefGoogle Scholar
  67. 67.
    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 365:1687–1717CrossRefGoogle Scholar
  68. 68.
    Camacho A (1966) Adrenal toxicity associated with the administration of an anticonvulsant drug. J Pediat 68:852–853Google Scholar
  69. 69.
    Cuzick J, Sestak I, Baum M et al (2010) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 11:1135–1141PubMedCrossRefGoogle Scholar
  70. 70.
    Chirgwin J, Sun Z, Smith I et al (2012) The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause. Breast Cancer Res Treat 131:295–306PubMedCrossRefGoogle Scholar
  71. 71.
    van de Velde CJ, Rea D, Seynaeve C et al (2011) Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet 377:321–331PubMedCrossRefGoogle Scholar
  72. 72.
    Wheler J, Johnson M, Seidman A et al (2006) Adjuvant therapy with aromatase inhibitors for postmenopausal women with early breast cancer: evidence and ongoing controversy. Semin Oncol 33:672–680PubMedCrossRefGoogle Scholar
  73. 73.
    Goss PE, Muss HB, Ingle JN (2008) Extended adjuvant endocrine therapy in breast cancer: current status and future directions. Clin Breast Cancer 8:411–417PubMedCrossRefGoogle Scholar
  74. 74.
    Mamounas EP, Jeong JH, Wickerham DL et al (2008) Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol 26:1965–1971PubMedCrossRefGoogle Scholar
  75. 75.
    Gray RG, Rea RW, Handley K et al. (2008) ATTOM (adjuvant Tamoxifen–To offer more?): randomized trial of 10 versus 5 years of adjuvant tamoxifen among 6,934 women with estrogen receptor-positive (ER +) or ER untested breast cancer—preliminary results. J Clin Oncol 26(suppl 513)Google Scholar
  76. 76.
    Peto R, Davies C et al (2007) ATLAS (Adjuvant Tamoxifen, Longer Against Shorter): International Randomized Trial of 10 versus 5 years of adjuvant tamoxifen among 11,500 women—preliminary results. Breast Cancer Res Treat 106(suppl; abstract 48)Google Scholar
  77. 77.
    Cuzick J (2007) Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet 369:1711–1723PubMedCrossRefGoogle Scholar
  78. 78.
    Fabian CJ (2007) The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer. Int J Clin Pract 61:2051–2063PubMedCrossRefGoogle Scholar
  79. 79.
    Gonzalez-Angulo AM, Litton JK et al (2009) High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller. J Clin Oncol 27:5700–5706PubMedCrossRefGoogle Scholar
  80. 80.
    Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMedCrossRefGoogle Scholar
  81. 81.
    von Minckwitz G, du Bois A, Schmidt M et al (2009) Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German Breast Group 26/breast international group 03–05 study. J Clin Oncol 27:1999–2006CrossRefGoogle Scholar
  82. 82.
    Geyer CE, Forster J, Lindquist D et al (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733–2743PubMedCrossRefGoogle Scholar
  83. 83.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672PubMedCrossRefGoogle Scholar
  84. 84.
    Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684PubMedCrossRefGoogle Scholar
  85. 85.
    Slamon D, Eiermann W, Robert N et al (2011) Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283PubMedCrossRefGoogle Scholar
  86. 86.
    Maurea N, Coppola C, Ragone G et al (2010) Women survive breast cancer but fall victim to heart failure: the shadows and lights of targeted therapy. J Cardiovasc Med 11:861–868CrossRefGoogle Scholar
  87. 87.
    Chen T, Xu T, Li Y et al (2011) Risk of cardiac dysfunction with trastuzumab in breast cancer patients: a meta-analysis. Cancer Treat Rev 37:312–320PubMedCrossRefGoogle Scholar
  88. 88.
    von Minckwitz G, Eidtmann H, Rezai M et al (2012) Neoadjuvant chemotherapy and bevacizumab for HER2negative breast cancer. N Engl J Med 366:299–309CrossRefGoogle Scholar
  89. 89.
    Bear HD, Tang G, Rastogi P et al (2012) Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med 366:310–320PubMedCrossRefGoogle Scholar
  90. 90.
    Gnant M, Mlineritsch B, Schippinger W et al (2009) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360:679–691PubMedCrossRefGoogle Scholar
  91. 91.
    Coleman RE, Marshall H, Cameron D et al (2011) Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med 365:1396–1405PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Manfred Kaufmann
    • 1
  • Gunter von Minckwitz
    • 2
  • Jonas Bergh
    • 3
    • 4
  • Pier-Franco Conte
    • 5
  • Sarah Darby
    • 6
  • Wolfgang Eiermann
    • 7
  • Antony Howell
    • 8
  • Marion Kiechle
    • 9
  • Davide Mauri
    • 10
  • Hans-Jörg Senn
    • 11
  • Giuseppe Viale
    • 12
  • Sibylle Loibl
    • 2
  1. 1.Department of Obstetrics and GynaecologyJ. W. Goethe UniversityFrankfurtGermany
  2. 2.German Breast GroupNeu-IsenburgGermany
  3. 3.Radiumhemmet, Karolinska OncologyStockholmSweden
  4. 4.Manchester UniversityManchesterUK
  5. 5.Divisione di Oncologia Medica 2Universitá die Padua Regione del VenetoPaduaItaly
  6. 6.Clinical Trial Service UnitUniversity of OxfordOxfordUK
  7. 7.Department of Obstetrics and GynecologyRot-Kreuz KrankenhausMunichGermany
  8. 8.The Christie Hospital and University Hospital of South ManchesterManchesterUK
  9. 9.Department of Obstetrics and GynecologyTechnical University MünchenMunichGermany
  10. 10.Department of Medical OncologyGeneral Hospital of LamiaLamiaGreece
  11. 11.Tumor und Brustzentrum ZeTuP St. Gallen and St. Gallen Oncology ConferencesSt. GallenSwitzerland
  12. 12.Department of PathologyIstituto Europeo di Oncologia, University of MilanMilanItaly

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