|Table of Contents|
Adjuvant systemic therapy for early breast cancer
Breast cancer-specific mortality has declined over the last two decades as a result of the introduction of screening programmes and advances in adjuvant systemic therapy. The most notable progress has been achieved in the case of Her2-positive disease, following the introduction of trastuzumab, a humanized monoclonal antibody targeting the extracellular domain ofHer2. Indeed, addition of trastuzumab to chemotherapy for a total duration of 1 year increases progression-free survival (PFS) as well as overall survival (OS) compared with chemotherapy alone. In hormone receptor-positive disease, treatment with aromatase inhibitors (AIs) prolongs PFS compared with tamoxifen, and in some clinical trials they have been found to increase OS also. Chemotherapy remains the mainstay of treatment for patients with triple-negative disease and also plays a role in Her2-positive and high-risk hormone receptor-positive tumours. Although, overall, only limited progress has been achieved in this field, most trials suggest that the introduction of taxanes has resulted in improved outcomes. Dose-dense chemotherapy is superior to older adjuvant regimens comprising 3-weekly administration of paclitaxel, while high-dose chemotherapy with autologous stem cell support currently has no place in the treatment of breast cancer. Neoadjuvant chemotherapy increases the rate of breast-conserving surgeries; importantly, the pathological complete remission (pCR) rate has been identified as a surrogate for improved OS in hormone receptor-negative patients. Thus, clinical trials have aimed to increase pCR rates by addition of further cytotoxic substances or biologicals such as trastuzumab, lapatinib or bevacizumab. However, the optimum treatment strategy for hormone receptor-negative patients without pCR remains elusive. This review discusses recent developments and open questions in the field of adjuvant systemic therapy for early breast cancer.
Alba E, Calvo L, Albanell J, et al. Chemotherapy (CT) versus hormone therapy (HT) as neoadjuvant treatment in luminal breast cancer: a multicenter, randomized phase II study (GEICAM/2006-03). J Clin Oncol 2010; 28(Suppl.15):Abstract 100.
Albain KS, Barlow WE, Ravdin PM, et al.; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet 2009; 374:2055–63. http://dx.doi.org/10.1016/S0140-6736(09)61523-3
American Cancer Society, Global cancer facts and Figures, 2nd edn. Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-027766.pdf (accessed 24 November 2011).
Antman K, Ayash L, Elias A, et al. A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy. J Clin Oncol 1992; 10:102–10.
Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. 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. http://dx.doi.org/10.1016/S1470-2045(07)70385-6
Bajetta E, Procopio G, Ferrari L, et al. A randomized, multicenter prospective trial assessing long-acting release octreotide pamoate plus tamoxifen as a first line therapy for advanced breast carcinoma. Cancer 2002; 94:299–304. http://dx.doi.org/10.1002/cncr.10239
Bartlett JMS, Brookes CL, van de Velde CJH, et al. Final results of a prospectively planned biomarker analysis: her1–3 as predictive markers of benefit from early treatment with aromatase inhibitors versus tamoxifen in the TEAM Pathology Sub-Study. Presented at the 33rd Annual San Antonio Breast Cancer Symposium, 8–12 December 2010, San Antonio, TX, USA (Abstract S2-4).
Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 2012; 379:633–40.
Baselga J, Tripathy D, Mendelsohn J, et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 1996; 14:737–44.
Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Breast and Bowel Project B-27. J Clin Oncol 2006; 24:2019–27. http://dx.doi.org/10.1200/JCO.2005.04.1665
Bear HD, Tang G, Rastogi P, et al. The effect on pCR of bevacizumab and/or antimetabolites added to standard neoadjuvant chemotherapy: NSABP protocol B-40. J Clin Oncol 2011; 29(Suppl.):Abstract LBA1005.
Bergman L, van Dongen JA, van Ooijen B, van Leeuwen FE. Should tamoxifen be a primary treatment choice for elderly breast cancer patients with locoregional disease? Breast Cancer Res Treat 1995; 34:77–83. http://dx.doi.org/10.1007/BF00666494
Berry DA, Ueno NT, Johnson MM, et al. High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials. J Clin Oncol 2011; 29:3214–23. http://dx.doi.org/10.1200/JCO.2010.32.5910
Bishop JF, Dewar J, Toner GC, et al. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol 1999; 17:2355–64.
Bonadonna G, Valagussa P. Dose–response effect of adjuvant chemotherapy in breast cancer. N Engl J Med 1981; 304:10–15. http://dx.doi.org/10.1056/NEJM198101013040103
Bonilla L, Ben-Aharon I, Vidal L, Gafter-Gvili A, Leibovici L, Stemmer SM. Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 2010; 102:1845–54. http://dx.doi.org/10.1093/jnci/djq409
Bonneterre J, Buzdar A, Nabholtz JM, et al.; Arimidex Writing Committee; Investigators Committee Members. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001; 92:2247–58. http://dx.doi.org/10.1002/1097-0142(20011101)92:9<2247::AID-CNCR1570>3.0.CO;2-Y
Bonneterre J, Roché H, Kerbrat P, et al. Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial. J Clin Oncol 2005; 23:2686–93. http://dx.doi.org/10.1200/JCO.2005.05.059
Burnell M, Levine M, Chapman JA, et al. A randomized trial of CEF versus dose dense EC followed by paclitaxel versus AC followed by paclitaxel in women with node positive or high risk node negative breast cancer, NCIC CTG MA.21: Results of an interim analysis. Presented at the 29th Annual San Antonio Breast Cancer Symposium; 14–17 December 2006, San Antonio, TX, USA.
Burstein HJ, Prestrud AA, Seidenfeld J, et al.; American Society of Clinical Oncology. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol 2010; 28: 3784–96. http://dx.doi.org/10.1200/JCO.2009.26.3756
Buzdar AU, Ibrahim NK, Francis D, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: Results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 2005; 23:3676–85. http://dx.doi.org/10.1200/JCO.2005.07.032
Buzdar AU, Xu B, Digumarti R, et al. Randomized phase II non-inferiority study (NO16853) of two different doses of capecitabine in combination with docetaxel for locally advanced/metastatic breast cancer. Ann Oncol 2012; 23:589–97. http://dx.doi.org/10.1093/annonc/mdr256
Buzdar AU. Preoperative chemotherapy treatment of breast cancer – a review. Cancer 2007; 110:2394–407.http://dx.doi.org/10.1002/cncr.23083
Citron ML, Berry DA, Cirrincione C, et al. 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 2003; 21:1431–9. http://dx.doi.org/10.1200/JCO.2003.09.081
Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999; 17: 2639–48.
DeFriend DJ, Howell A, Nicholson RI, et al. Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res 1994; 54:408–14.
Di Leo A, Gancberg D, Larsimont D, et al. HER-2 amplification and topoisomerase IIα gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res 2002; 8:1107–16.
Dutertre M, Smith CL. Molecular mechanisms of selective estrogen receptor modulator (SERM) action. JPharmacol Exp Ther 2000; 295:431–7.
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378:771–84.
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. http://dx.doi.org/10.1016/S0140-6736(05)66544-0
Early Breast Cancer Trialists’ Collaborative Group: adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials. Lancet 2008; 371:29–40. http://dx.doi.org/10.1016/S0140-6736(08)60069-0
Early Breast Cancer Trialists’ Collaborative Group: polychemotherapy for early breast cancer: an overview of randomized trails. Lancet 1998; 352:930–42. http://dx.doi.org/10.1016/S0140-6736(98)03301-7
Eiermann W, Pienkowski T, Crown J, et al. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 Trial. J Clin Oncol 2011; 29:3877–84. http://dx.doi.org/10.1200/JCO.2010.28.5437
Eiermann W, Paepke S, Appfelstaedt J, et al.; Letrozole Neo-Adjuvant Breast Cancer Study Group. Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Ann Oncol 2001;12: 1527–32. http://dx.doi.org/10.1023/A:1013128213451
Ellis MJ, Suman VJ, Hoog J, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype – ACOSOG Z1031. J Clin Oncol 2011; 29:2342–9. http://dx.doi.org/10.1200/JCO.2010.31.6950
Ellis P, Barrett-Lee P, Johnson L, et al.; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet 2009; 373:1681–92. http://dx.doi.org/10.1016/S0140-6736(09)60740-6
Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on loco-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997; 15:2483–93.
Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin–cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 1990; 8:1485–96.
Francis P, Crown J, Di Leo A, et al.; BIG 02-98 Collaborative Group. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial. J Natl Cancer Inst 2008; 100:121–33. http://dx.doi.org/10.1093/jnci/djm287
Gazet JC, Ford HT, Coombes RC, Bland JM, Sutcliffe R, Quilliam J, Lowndes S. Prospective randomized trial of tamoxifen vs surgery in elderly patients with breast cancer. Eur J Surg Oncol 1994; 20:207–14.
Gerber H, Eidtmann H, Rezai M, et al. Neoadjuvant bevacizumab and anthracycline–taxane-based chemotherapry in 686 triple-negative primary breast cancers: Seconday endpoint analysis of the GeparQuinto study (GBG 44). J Clin Oncol 2011; 29(Suppl.15):Abstract 1006.
Gianni L, Pienkowski T, Im YH, et al. 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 2012; 13:25–32.http://dx.doi.org/10.1016/S1470-2045(11)70336-9
Gianni L, Dafni U, Gelber RD, et al.; Herceptin Adjuvant (HERA) Trial Study Team. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 2011; 12:236–44. http://dx.doi.org/10.1016/S1470-2045(11)70033-X
Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 2010; 375:377–84. http://dx.doi.org/10.1016/S0140-6736(09)61964-4
Gnant M, Mlineritsch B, Schippinger W, et al.; ABCSG-12 Trial Investigators, Marth C. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 2009; 360:679–91. http://dx.doi.org/10.1056/NEJMoa0806285
Goel S, Sharma R, Hamilton A, Beith J. LHRH agonists for adjuvant therapy of early breast cancer in premenopausal women. Cochrane Database Syst Rev 2009;CD004562.
Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ; 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 2011; 22:1736–47. http://dx.doi.org/10.1093/annonc/mdr304
Goldstein LJ, O’Neill A, Sparano JA, et al. Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American Breast Cancer Intergroup Trial E 2197. J Clin Oncol 2008; 26:4092–9. http://dx.doi.org/10.1200/JCO.2008.16.7841
Gonzalez-Angulo AM, Litton JK, Broglio KR, et al. 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 2009; 27:5700–6. http://dx.doi.org/10.1200/JCO.2009.23.2025
Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003; 349:1793–802. http://dx.doi.org/10.1056/NEJMoa032312
Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: The M.D. Anderson Cancer Center experience. J Clin Oncol 2006; 24:4107–15. http://dx.doi.org/10.1200/JCO.2005.04.9551
Henderson IC, Berry DA, Demetri GD, et al. Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 2003; 21:976–83. http://dx.doi.org/10.1200/JCO.2003.02.063
Horobin JM, Preece PE, Dewar JA, Wood RA, Cuschieri A. Long-term follow-up of elderly patients with locoregional breast cancer treated with tamoxifen only. Br J Surg 1991; 78:213–17. http://dx.doi.org/10.1002/bjs.1800780228
Jakesz R, Gnant M, Griel R, et al. Tamoxifen and anastrozole as a sequencing strategy in postmenopausal women with hormone-responsive early breast cancer: updated data from the Austrian breast and colorectal cancer study group trial 8. Presented at the 31st Annual San Antonio Breast Cancer Symposium, 10–14 December 2008, San Antonio, TX, USA.
Jakesz R, Greil R, Gnant M, et al.; Austrian Breast and Colorectal Cancer Study Group. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst 2007; 99:1845–53. http://dx.doi.org/10.1093/jnci/djm246
Joensuu H, Kellokumpu-Lehtinen P-L, Bono P, et al; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006; 354:809–20. http://dx.doi.org/10.1056/NEJMoa053028
Jones S, Holmes FA, O’Shaughnessy J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol 2009; 27:1177–83. http://dx.doi.org/10.1200/JCO.2008.18.4028
Jones SE, Savin MA, Holmes FA, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 2006, 24:5381–7. http://dx.doi.org/10.1200/JCO.2006.06.5391
Kaufmann M, Jonat W, Hilfrich J, 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. http://dx.doi.org/10.1200/JCO.2006.08.8054
Krainick-Strobel UE, Lichtenegger W, Wallwiener D, et al. Neoadjuvant letrozole in postmenopausal oestrogen and/or progesterone receptor positive breast cancer: a phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy. BMC Cancer 2008; 8:62. http://dx.doi.org/10.1186/1471-2407-8-62
Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 1999; 17:460–9.
Mackey J, McLeod D, Ragaz J, et al. Adjuvant targeted therapy in early breast cancer. Cancer 2009; 115:1154–68. http://dx.doi.org/10.1002/cncr.24114
Madarnas Y, Trudeau M, Franek JA, McCready D, Pritchard KI, Messersmith H. Adjuvant/neoadjuvant trastuzumab therapy in women with HER-2/neu-overexpressing breast cancer: a systematic review. Cancer Treat Rev 2008; 34:539–57. http://dx.doi.org/10.1016/j.ctrv.2008.03.013
Mamounas EP, Bryant J, Lembersky B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol 2005; 23:3686–96. http://dx.doi.org/10.1200/JCO.2005.10.517
Mamounas EP, Jeong JH, Wickerham DL, et al. 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 2008; 26:1965–71. http://dx.doi.org/10.1200/JCO.2007.14.0228
Mano MS, Rosa DD, De Azambuja E, Ismael GF, Durbecq V. The 17q12–q21 amplicon: Her2 and topoisomerase-IIα and their importance to the biology of solid tumours. Cancer Treat Rev 2007; 33:64–77. http://dx.doi.org/10.1016/j.ctrv.2006.10.001
Marchionni L, Wilson RF, Wolff AC, et al. Systematic review: gene expression profiling assays in early-stage breast cancer. Ann Intern Med 2008; 148:358–69.
Martin M, Pienkowski T, Mackey J, et al.; Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005; 353: 2302–13. http://dx.doi.org/10.1056/NEJMoa043681
Martín M, Seguí MA, Antón A, et al.; GEICAM 9805 Investigators. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med 2010; 363:2200–10. http://dx.doi.org/10.1056/NEJMoa0910320
Martin M, Villar A, Sole-Calvo A, et al.; GEICAM Group (Spanish Breast Cancer Research Group), Spain. Doxorubicin in combination with fluorouracil and cyclophosphamide (iv FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (iv CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. Ann Oncol 2003; 14:833–42. http://dx.doi.org/10.1093/annonc/mdg260
Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 2005; 23:4265–74. http://dx.doi.org/10.1200/JCO.2005.04.173
Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 2005; 97:188–94.http://dx.doi.org/10.1093/jnci/dji021
Mlineritsch B, Tausch C, Singer C, et al.; Austrian Breast, Colorectal Cancer Study Group (ABCSG). Exemestane as primary systemic treatment for hormone receptor positive post-menopausal breast cancer patients: a phase II trial of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-17). Breast Cancer Res Treat 2008; 112:203–13. http://dx.doi.org/10.1007/s10549-007-9843-x
Mustacchi G, Ceccherini R, Milani S, et al.; Italian Cooperative Group GRETA. Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial. Ann Oncol 2003; 14:414–20. http://dx.doi.org/10.1093/annonc/mdg117
Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to Her2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 2006; 3:269–80. http://dx.doi.org/10.1038/ncponc0509
Paik S, Hazan R, Fisher ER, et al. Pathologic finding from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein expression in primary breast cancer. J Clin Oncol 1990; 8:103–12.
Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006; 24:3726–34. http://dx.doi.org/10.1200/JCO.2005.04.7985
Paridaens R, Biganzoli L, Bruning P, et al. Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer randomized study with cross-over. J Clin Oncol 2000; 18:724–33.
Paridaens R, Dirix L, Lohrisch C, et al.; European Organization for the Research and Treatment of Cancer (EORTC) – Investigational Drug Branch for Breast Cancer (IDBBC). Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. Ann Oncol 2003; 14:1391–8. http://dx.doi.org/10.1093/annonc/mdg362
Perez E, Suman V, Davidson N, et al. Results of chemotherapy alone, with sequential or concurrent addition of 52 weeks of trastuzumab in the NCCTG N9831 HER2-positive adjuvant breast cancer trial, 9–13 December 2009, San Antonio, TX, USA.
Perez EA, Rodeheffer R. Clinical cardiac tolerability of trastuzumab. J Clin Oncol 2004; 22:322–9. http://dx.doi.org/10.1200/JCO.2004.01.120
Perez EA, Romond EH, Suman VJ, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol 2011; 29:3366–73. http://dx.doi.org/10.1200/JCO.2011.35.0868
Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast cancer. Nature 2000; 406:747–52. http://dx.doi.org/10.1038/35021093
Peto R. Early Breast Cancer Trialists’ Collaborative Group. The worldwide overview: new results for systemic adjuvant therapies. Presented at the 30th Annual San Antonio Breast Cancer Symposium, 13–16 December 2007, San Antonio, TX, USA.
Piccart MJ, Di Leo A, Beauduin M, et al. 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 2001; 19:3103–10.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al.; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 53:1659–72. http://dx.doi.org/10.1056/NEJMoa052306
Regan MM, Neven P, Giobbie-Hurder A, et al.; for the members of the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncol 2011; 12:1101–8. http://dx.doi.org/10.1016/S1470-2045(11)70270-4
Ring AE, Ellis PA. Taxanes in the treatment of early breast cancer. Cancer Treat Rev 2005; 31:618–27. http://dx.doi.org/10.1016/j.ctrv.2005.09.005
Robertson JF, Nicholson RI, Bundred NJ, et al. Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer. Cancer Res 2001; 61:6739–46.
Robertson JF, Semiglazov V, Nemsadze G, et al.; Study 41 Investigators. Effects of fulvestrant 250mg in premenopausal women with oestrogen receptor-positive primary breast cancer. Eur J Cancer 2007; 43:64–70. http://dx.doi.org/10.1016/j.ejca.2006.08.019
Robertson JF, Todd JH, Ellis IO, Elston CW, Blamey RW. Comparison of mastectomy with tamoxifen for treating elderly patients with operable breast cancer. BMJ 1988; 297:511–14. http://dx.doi.org/10.1136/bmj.297.6647.511
Roché H, Fumoleau P, Spielmann M, et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol 2006; 24:5664–71. http://dx.doi.org/10.1200/JCO.2006.07.3916
Rodenhuis S, Bontenbal M, Beex LV, et al.; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med 2003; 349:7–16. http://dx.doi.org/10.1056/NEJMoa022794
Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353:1673–84. http://dx.doi.org/10.1056/NEJMoa052122
Rowinsky EK, Cazenave LA, Donehower RC. Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst 1990; 82:1247–59. http://dx.doi.org/10.1093/jnci/82.15.1247
Scaltriti M, Verma C, Guzman M, et al. Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene 2009; 28:803–14. http://dx.doi.org/10.1038/onc.2008.432
Semiglazov VF, Semiglazov VV, Dashyan GA, et al. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer 2007; 110:244–54. http://dx.doi.org/10.1002/cncr.22789
Seo JH, Kim YH, Kim JS. Meta-analysis of pre-operative aromatase inhibitor versus tamoxifen in postmenopausal woman with hormone receptor-positive breast cancer. Cancer Chemother Pharmacol 2009; 63:261–6. http://dx.doi.org/10.1007/s00280-008-0735-5
Slamon D, Eiermann W, Robert N, et al.; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011; 365:1273–83. http://dx.doi.org/10.1056/NEJMoa0910383
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344:783–92. http://dx.doi.org/10.1056/NEJM200103153441101
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 1987; 235:177–82. http://dx.doi.org/10.1126/science.3798106
Smith I, Procter M, Gelber RD, et al.; HERA study team. Two year follow-up of trastuzumab after adjuvant chemotherapy in Her2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369:29–36. http://dx.doi.org/10.1016/S0140-6736(07)60028-2
Smith IE, Dowsett M, Ebbs SR, et al.; IMPACT Trialists Group. 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 2005; 23:5108–16. http://dx.doi.org/10.1200/JCO.2005.04.005
Smith IE, Dowsett M. Aromatase inhibitors in breast cancer. N Engl J Med 2003; 348:2431–42. http://dx.doi.org/10.1056/NEJMra023246
Spielmann M, Roché H, Delozier T, et al. Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol 2009; 27:6129–34. http://dx.doi.org/10.1200/JCO.2009.23.0946
Steger G, Greil R, Jakesz R, et al. Final results of ABCSG-24, a randomized phase III study comparing epirubicin, docetaxel, and capecitabine (EDC) to epirubicin and docetaxel (ED) as neoadjuvant treatment for early breast cancer and comparing ED/EDC + trastuzumab (T) to ED/EDC as neoadjuvant treatment for early HER-2 positive breast cancer. Cancer Res 2009; 69(Suppl. 24):Abstract 1081.
Swain SM, Jeong JH, Geyer CE Jr, et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 2010; 362:2053–65. http://dx.doi.org/10.1056/NEJMoa0909638
Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007; 25:4414–22. http://dx.doi.org/10.1200/JCO.2007.10.6823
Untch M, Fasching PA, Konecny GE, et al. 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 2011; 29:3351–7.http://dx.doi.org/10.1200/JCO.2010.31.4930
Untch M, Loibl S, Bischoff J, et al. Lapatinib vs trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy: primary efficacy endpoint analysis of the GeparQuinto study (GBG 44). Cancer Res 2010; 70(Suppl.):Abstract S3-1.
van de Velde CJ, Rea D, Seynaeve C, et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet 2011; 377:321–31. http://dx.doi.org/10.1016/S0140-6736(10)62312-4
Vici P, Brandi M, Giotta F, et al. A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study. Ann Oncol 2011 [Epub ahead of print].
von Minckwitz G, Rezai M, Loibl S, et al. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol 2010; 28:2015–23. http://dx.doi.org/10.1200/JCO.2009.23.8303
von Minckwitz G, Untch M, Nüesch E, et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat 2011; 125:145–56. http://dx.doi.org/10.1007/s10549-010-1228-x
Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: 9-year results from National Surgical Breast and Bowel Project B-18. J Natl Cancer Inst 2001; 30:96–102.
Young OE, Renshaw L, Macaskill EJ, et al. Effects of fulvestrant 750mg in premenopausal women with oestrogen-receptor-positive primary breast cancer. Eur J Cancer 2008; 44:391–9. http://dx.doi.org/10.1016/j.ejca.2007.11.007