Adjuvant chemotherapy for early female breast cancer: A systematic review of the evidence for the 2014 cancer care Ontario systemic therapy guideline

Current Oncology

Volumn 22, Issue , 2015, Pages S82-S94

  Gandhi, S ^a   Fletcher, G G ^b   Eisen, A ^a   Mates, M ^c   Freedman, O C ^d   Dent, S F ^e   Trudeau, M E ^a  

^a SUNNYBROOK RESEARCH INSTITUTE   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

^c QUEEN S UNIVERSITY   (Canada)

^d Durham Regional Cancer Centre   (Canada)

^e OTTAWA REGIONAL CANCER CENTRE   (Canada)

Author keywords

Adjuvant; Chemotherapy; Cytotoxic; Drug therapy; Early breast cancer; Systemic treatment

Indexed keywords

ANTHRACYCLINE; AROMATASE INHIBITOR; BEVACIZUMAB; BISPHOSPHONIC ACID DERIVATIVE; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIRUBICIN; FLUOROURACIL; GONADORELIN AGONIST; METFORMIN; METHOTREXATE; NELIPEPIMUT S; PACLITAXEL; TAMOXIFEN; TRASTUZUMAB;

ADJUVANT CHEMOTHERAPY; ARTICLE; BREAST CANCER; CANCER SURVIVAL; CARDIOTOXICITY; CLINICAL TRIAL (TOPIC); DRUG DOSE REGIMEN; DRUG WITHDRAWAL; HEART DISEASE; HORMONAL THERAPY; HUMAN; HYPERTENSION; LEUKEMIA; META ANALYSIS (TOPIC); PRACTICE GUIDELINE; SYSTEMATIC REVIEW;

EID: 84931005393     PISSN: None     EISSN: 17187729     Source Type: Journal    
DOI: 10.3747/co.22.2321     Document Type: Article

References (147)

1. Berry DA, Cronin KA, Plevritis SK, et al. on behalf of the Cancer Intervention and Surveillance Modeling Network (cisnet) collaborators. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 2005;353:1784-92.
2. Eisen A, Srikanthan A, Yeung L, Iyer R, Trudeau M. Provincial variation in utilization of adjuvant chemotherapy regimens in early stage breast cancer: data from the Cancer Care Ontario New Drug Funding Program (ndfp) [abstract P3-12-1]. Cancer Res 2013;73(suppl):.
3. Eisen A, Fletcher GG, Gandhi S, et al. Optimal Systemic Therapy for Early Female Breast Cancer. Evidence-based series 1-21. Toronto, ON: Cancer Care Ontario; 2014. [Available online at: https://www.cancercare.on.ca/toolbox/qualityguide lines/diseasesite/breast-ebs/; cited August 19, 2014]
4. Singletary SE, Allred C, Ashley P, et al. Part vii. Breast. In: Greene FL, Page DL, Fleming ID, et al., eds. American Joint Committee on Cancer Staging Manual. 6th ed. New York, NY: Springer-Verlag; 2002: 221-40.
5. Singletary SE, Allred C, Ashley P, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 2002;20:3628-36.
6. Shea BJ, Grimshaw JM, Wells GA, et al. Development of amstar: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol 2007;7:10. [Available online at: http://www.ncbi.nlm.nih. gov/pmc/articles/PMC1810543/pdf/1471-2288-7-10.pdf; cited December 7, 2013]
7. Simmonds MC, Higgins JP, Stewart LA, Tierney JF, Clarke MJ, Thompson SG. Meta-analysis of individual patient data from randomized trials: a review of methods used in practice. Clin Trials 2005;2:209-17.
8. Peto R, Davies C, Godwin J, et al. on behalf of the Early Breast Cancer Trialists' Collaborative Group. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2012;379:432-44.
9. Early Breast Cancer Trialists' Collaborative Group. 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.
10. Davies C, Godwin J, Gray R, et al. on behalf of the Early Breast Cancer Trialists' Collaborative Group. 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.
11. Clarke M, Coates AS, Darby SC, et al. on behalf of the 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.
12. Early Breast Cancer Trialists' Collaborative Group. Ovarian ablation in early breast cancer: overview of the randomised trials. Lancet 1996;348:1189-96.
13. Amadori D, Nanni O, Volpi A, et al. Phase iii randomized multicenter study on the effects of adjuvant cmf in patients with node-negative, rapidly proliferating breast cancer: twelve-year results and retrospective subgroup analysis. Breast Cancer Res Treat 2008;108:259-64.
14. Amadori D, Nanni O, Marangolo M, et al. Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with node-negative, rapidly proliferating breast cancer: a randomized multicenter study. J Clin Oncol 2000;18:3125-34.
15. Taucher S, Steger GG, Jakesz R, et al. on behalf of the Austrian Breast and Colorectal Cancer Study Group-07. The potential risk of neoadjuvant chemotherapy in breast cancer patients-results from a prospective randomized trial of the Austrian Breast and Colorectal Cancer Study Group (abcsg-07). Breast Cancer Res Treat 2008;112:309-16.
16. Muss HB, Berry DA, Cirrincione CT, et al. on behalf of the calgb Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med 2009;360:2055-65. [Erratum in: N Engl J Med 2009;361:1714]
17. Kornblith AB, Lan L, Archer L, et al. Quality of life of older patients with early-stage breast cancer receiving adjuvant chemotherapy: a companion study to Cancer and Leukemia Group B 49907. J Clin Oncol 2011;29:1022-8.
18. Ejlertsen B, Mouridsen HT, Jensen MB, et al. on behalf of the Danish Breast Cancer Cooperative Group. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer 2010;116:2081-9.
19. Ejlertsen B, Mouridsen HT, Jensen MB. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in premonopausal patients with node-positive breast cancer: indirect comparison of dose and schedule in dbcg trials 77, 82, and 89. Acta Oncol 2008;47:662-71.
20. Ejlertsen B, Mouridsen HT, Jensen MB, et al. Improved outcome from substituting methotrexate with epirubicin: results from a randomised comparison of cmf versus cef in patients with primary breast cancer. Eur J Cancer 2007;43:877-84.
21. Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, et al. Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized finxx trial. J Clin Oncol 2012;30:11-18.
22. Canney P, Coleman R, Morden J, et al. tact2 trial in early breast cancer (ebc): differential rates of amenorrhoea in premenopausal women following adjuvant epirubicin (e) or accelerated epirubicin (ae) followed by capecitabine (x) or cmf (cruk/05/019) [abstract 200]. Eur J Cancer 2012;48(suppl):S102.
23. Canney P, Barrett-Lee P, Bartlett J, et al. The U.K. tact2 trial: non-inferiority of capecitabine compared with cmf after epirubicin in patients requiring chemotherapy for early breast cancer (ebc) (cruk/05/019) [abstract 94]. Eur J Cancer 2014;50:S99-S100.
24. Helwick C. Dose-dense chemotherapy in breast cancer: epirubicin-based regimens studied in German and UK trials. The ASCO Post 2013;4:. [Available online at: http://www.asco post.com/issues/march-1,-2013/dose-dense-chemotherapy-inbreast-cancer-epirubicin-based-regimens-studied-in-germanand-uk-trials.aspx; cited June 18, 2014]
25. Velikova G, Barrett-Lee P, Bloomfield D, et al. Quality of life results of the U.K. tact2 trial: more intensive chemotherapy for early breast cancer has a measurable impact on patientreported symptoms and functioning (cruk/05/019) [abstract 227]. Eur J Cancer 2014;50:S109.
26. Ohno S, Chow LWC, Sato N, et al. Randomized trial of preoperative docetaxel with or without capecitabine after 4 cycles of 5-fluorouracil-epirubicin-cyclophosphamide (fec) in early-stage breast cancer: exploratory analyses identify Ki67 as a predictive biomarker for response to neoadjuvant chemotherapy. Breast Cancer Res Treat 2013;142:69-80.
27. Pippen JE, Paul D, Stokoe CT, et al. Randomized, phase iii study of adjuvant doxorubicin plus cyclophosphamide (ac) → docetaxel (t) with or without capecitabine (x) in high-risk early breast cancer: exploratory Ki-67 analyses [abstract 500]. J Clin Oncol 2011;29:. [Available online at: http://meetinglibrary. asco.org/content/78730-102; cited December 26, 2014]
28. O'Shaughnessy J, Paul D, Stokoe C, et al. First efficacy results of a randomized, open-label, phase iii study of adjuvant doxorubicin plus cyclophosphamide, followed by docetaxel with or without capecitabine, in high-risk early breast cancer [abstract S4-2]. Cancer Res 2010;70:85s.
29. O'Shaughnessy J, Pippen JE, Paul D, et al. Adjuvant capecitabine for invasive lobular/mixed early breast cancer (ebc): uson 01062 exploratory analyses [abstract 547]. J Clin Oncol 2012;30:. [Available online at: http://meetinglibrary. asco.org/content/101121-114; cited December 26, 2014]
30. Bermejo B, Ruiz A, Borrego MR, et al. Randomized phase iii study of adjuvant chemotherapy for node-positive early breast cancer (bc) patients (pts) comparing epirubicin plus cyclophosphamide followed by docetaxel (ec-t) versus epirubicin plus docetaxel followed by capecitabine (et-x): efficacy analysis of the geicam/2003-10 trial [abstract 1027]. J Clin Oncol 2013;31:. [Available online at: http://meetinglibrary.asco.org/ content/114381-132; cited December 26, 2014]
31. Watanabe T, Sano M, Takashima S, et al. Oral uracil and tegafur compared with classic cyclophosphamide, methotrexate, fluorouracil as postoperative chemotherapy in patients with node-negative, high-risk breast cancer: National Surgical Adjuvant Study for Breast Cancer 01 trial. J Clin Oncol 2009;27:1368-74.
32. Hara F, Watanabe T, Shimozuma K, Ohashi Y. Efficacy, toxicity and quality of life in older patients with early-stage breast cancer treated with oral tegafur-uracil or classical cmf (cyclophosphamide, methotrexate, and fluorouracil): an exploratory analysis of national surgical adjuvant study for breast cancer (n-sas bc) 01 trial [abstract P1-13-10]. Cancer Res 2012;72(suppl):.
33. Ejlertsen B, Jensen MB, Elversang J, et al. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage ii breast cancer. Eur J Cancer 2013;49:2986-94.
34. Colleoni M. International Breast Cancer Study Group (ibcsg) trial 22-00: low-dose cytotoxics as maintenance "anti-angiogenesis treatment" following adjuvant induction chemotherapy for patients with er-negative and pgr-negative breast cancer [abstract OT2-01-01]. Cancer Res 2011;71(suppl):.
35. Wardley AM, Hiller L, Howard HC, et al. on behalf of the tango Trial Collaborators. tango: a randomised phase iii trial of gemcitabine in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy for early breast cancer: a prospective pulmonary, cardiac and hepatic function evaluation. Br J Cancer 2008;99:597-603.
36. Earl HM, Vallier AL, Hiller L, et al. on behalf of the neo-tango investigators. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (neo-tango): an open-label, 2×2 factorial randomised phase 3 trial. Lancet Oncol 2014;15:201-12.
37. Toi M, Ohno S, Sato N, et al. Preoperative docetaxel (t) with or without capecitabine (x) following epirubicin, 5-fluorouracil and cyclophosphamide (fec) in patients with operable breast cancer (ootr N003): results of comparative study and predictive marker analysis [abstract P1-14-02]. Cancer Res 2012;72(suppl):.
38. Schneeweiss A, Marme F, Ruiz A, et al. A randomized phase ii trial of doxorubicin plus pemetrexed followed by docetaxel versus doxorubicin plus cyclophosphamide followed by docetaxel as neoadjuvant treatment of early breast cancer. Ann Oncol 2011;22:609-17.
39. de Azambuja E, Paesmans M, Beauduin M, et al. Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study. J Clin Oncol 2009;27:720-5.
40. Kimura M, Tominaga T, Takatsuka Y, et al. on behalf of the Adjuvant CEF Research Group for Breast Cancer. Randomized trial of cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil with node-positive breast cancer in Japan. Breast Cancer 2010;17:190-8.
41. Amadori D, Silvestrini R, De Lena M, et al. Randomized phase iii trial of adjuvant epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (cmf) versus cmf followed by epirubicin in patients with node-negative or 1-3 node-positive rapidly proliferating breast cancer. Breast Cancer Res Treat 2011;125:775-84.
42. Rocca A, Bravaccini S, Scarpi E, et al. Benefit from anthracyclines in relation to biological profiles in early breast cancer. Breast Cancer Res Treat 2014;144:307-18.
43. Cheang MC, Voduc KD, Tu D, et al. Responsiveness of intrinsic subtypes to adjuvant anthracycline substitution in the ncic ctg ma.5 randomized trial. Clin Cancer Res 2012;18:2402-12.
44. Bartlett JM, Munro AF, Dunn JA, et al. Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (neat/BR9601). Lancet Oncol 2010;11:266-74.
45. Poole CJ, Earl HM, Hiller L, et al. on behalf of the neat investigators and the sctbg. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med 2006;355:1851-62.
46. Earl HM, Hiller L, Dunn JA, et al. on behalf of the neat investigators and the sctbg. Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (cmf) vs cmf in early breast cancer: results with over 7 years median follow-up from the randomised phase iii neat/BR9601 trials. Br J Cancer 2012;107:1257-67.
47. Earl HM, Hiller L, Dunn JA, et al. on behalf of neat investigators. neat: National Epirubicin Adjuvant Trial-toxicity, delivered dose intensity and quality of life. Br J Cancer 2008;99:1226-31.
48. van Nes JG, Putter H, Julien JP, et al. on behalf of the Cooperating Investigators of the eortc. Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the eortc trial 10902. Breast Cancer Res Treat 2009;115:101-13.
49. Budd GT, Barlow WE, Moore HCF, et al. S0221: comparison of two schedules of paclitaxel as adjuvant therapy for breast cancer [abstract CRA1008]. J Clin Oncol 2013;31:. [Available online at: http://meetinglibrary.asco.org/content/108457-132; cited December 27, 2014]
50. Budd GT, Barlow WE, Moore HCF, et al. First analysis of swog S0221: a phase iii trial comparing chemotherapy schedules in high-risk early breast cancer [abstract 1004]. J Clin Oncol 2011;29:. [Available online at: http://meetinglibrary.asco.org/ content/74054-102; cited December 27, 2014]
51. Lee KS, Ro J, Nam BH, et al. A randomized phase-iii trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage ii/iii breast cancer. Breast Cancer Res Treat 2008;109:481-9.
52. Burnell M, Levine MN, Chapman JA, et al. Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol 2010;28:77-82.
53. Janni W, Harbeck N, Sommer HL, et al. on behalf of the success study group. Sequential treatment with epirubicin/ cyclophosphamide, followed by docetaxel versus fec120 in the adjuvant treatment of node-positive breast cancer patients: final survival analysis of the German adebar phase iii study [abstract 1081]. J Clin Oncol 2012;30:. [Available online at: http://meetinglibrary.asco.org/content/96324-114; cited December 27, 2014]
54. Schoenherr A, Kiechle M, Harbeck N, et al. Toxicity analysis of the adebar-trial: sequential anthracycline-taxane compared to fec120 in adjuvant treatment of high risk breast cancer patients [abstract FV-Onko 03.15]. Arch Gynecol Obstet 2010;282(suppl 1):S47.
55. Kerbrat P, Coudert B, Asselain B, et al. Optimal duration of adjuvant chemotherapy for high risk node negative breast cancer patients: 6-year results of the prospective randomized phase iii trial pacs 05 [abstract P1-13-04]. Cancer Res 2012;72(suppl 3):.
56. Ellis P, Barrett-Lee P, Johnson L, et al. on behalf of the tact trial management group and the 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.
57. Joensuu H, Bono P, Kataja V, et al. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the finher trial. J Clin Oncol 2009;27:5685-92.
58. Ladoire S, Mignot G, Dalban C, et al. Foxp3 expression in cancer cells and anthracyclines efficacy in patients with primary breast cancer treated with adjuvant chemotherapy in the phase iii unicancer-pacs 01 trial. Ann Oncol 2012;23:2552-6.
59. Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol 2008;26:778-85. [Erratum in: J Clin Oncol 2008;26:793]
60. 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.
61. Pusztai L, Jeong J-H, Gong Y, et al. Evaluation of microtubuleassociated protein-Tau expression as a prognostic and predictive marker in the nsabp-B 28 randomized clinical trial. J Clin Oncol 2009;27:4287-92.
62. 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 2012;23:1121-9.
63. Henderson IC, Berry DA, Demetri GD, et al. 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 2003;21:976-83.
64. Sartor CI, Peterson BL, Woolf S, et al. Effect of addition of adjuvant paclitaxel on radiotherapy delivery and locoregional control of node-positive breast cancer: Cancer and Leukemia Group B 9344. J Clin Oncol 2005;23:30-40.
65. Hayes DF, Thor AD, Dressler LG, et al. on behalf of the Cancer and Leukemia Group B (calgb) investigators. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 2007;357:1496-506.
66. Berry D, Thor A, Jewell SD, et al. Benefits of adding paclitaxel to adjuvant doxorubicin/cyclophosphamide depending on HER2 & er status: analysis of tumor tissue microarrays and immunohistochemistry in calgb 9344 (Intergroup 0148) [abstract 606]. Cancer Res 2009;69(suppl):.
67. Lara JF, Thor AD, Dressler LG, et al. on behalf of the Cancer and Leukemia Group B. p53 Expression in nodepositive breast cancer patients: results from the Cancer and Leukemia Group B 9344 trial (159905). Clin Cancer Res 2011;17:5170-8.
68. Cognetti F, De Laurentiis M, De Matteis A, et al. Sequential epirubicin-docetaxel-cmf as adjuvant therapy for node-positive early stage breast cancer: updated results of the taxit216 randomized trial [abstract 1820]. Ann Oncol 2008;19(suppl 8):viii77.
69. Francis P, Crown J, Di Leo A, et al. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial. J Natl Cancer Inst 2008;100:121-33. [Erratum in: J Natl Cancer Inst 2008;100:1655]
70. Oakman C, Francis PA, Crown J, et al. Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the Breast International Group 02-98 phase iii trial. Ann Oncol 2013;24:1203-11.
71. Fernandez-Cuesta L, Oakman C, Falagan-Lotsch P, et al. Prognostic and predictive value of TP53 mutations in nodepositive breast cancer patients treated with anthracycline-or anthracycline/taxane-based adjuvant therapy: results from the big 02-98 phase iii trial. Breast Cancer Res 2012;14:R70. [Available online at: http://breast-cancer-research.com/ content/pdf/bcr3179.pdf; cited July 6, 2012]
72. Martin M, Ruiz A, Ruiz Borrego M, et al. Fluorouracil, doxorubicin, and cyclophosphamide (fac) versus fac followed by weekly paclitaxel as adjuvant therapy for high-risk, nodenegative breast cancer: results from the geicam/2003-02 study. J Clin Oncol 2013;31:2593-9.
73. Delbaldo C, Serin D, Mousseau M, et al. on behalf of the Association Européenne de Recherche en Oncologie (aero). A phase iii adjuvant randomised trial of 6 cycles of 5-fluorouracil-epirubicine-cyclophosphamide (fec100) versus 4 fec100 followed by 4 Taxol (fec-t) in node positive breast cancer patients (trial B2000). Eur J Cancer 2014;50:23-30.
74. Martin M, Rodriguez-Lescure A, Ruiz A, et al. on behalf of the geicam 9906 Study Investigators. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst 2008;100:805-14.
75. Martin M, Rodriguez-Lescure A, Ruiz A, et al. Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer. Breast Cancer Res Treat 2010;123:149-57.
76. Fountzilas G, Dafni U, Gogas H, et al. on behalf of the Hellenic Cooperative Oncology Group. Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and cmf in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase iii trial he 10/00. Ann Oncol 2008;19:853-60.
77. Gogas H, Dafni U, Karina M, et al. Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase iii trial. Breast Cancer Res Treat 2012;132:609-19.
78. Polyzos A, Malamos N, Boukovinas I, et al. fec versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (horg). Breast Cancer Res Treat 2010;119:95-104.
79. Nitz U, Huober J, Lisboa B, et al. Superiority of sequential docetaxel over standard fe100c in patients with intermediate risk breast cancer: survival results of the randomized Intergroup phase iii trial ec-doc [abstract 78]. Cancer Res 2009;69(suppl):.
80. Huober J, Gluz O, Hartmann A, et al. Evidence for predictive and prognostic impact of molecular classification in taxanebased chemotherapy in intermediate risk breast cancer-an analysis of the wsg ec-doc trial [abstract P2-09-14]. Cancer Res 2010;70:.
81. Nitz U, Gluz O, Liedtke C, et al. Comparison of predictive and prognostic impact of molecular subtypes and central grade regarding taxane-based therapy in intermediate-risk breast cancer: results from the ec-doc trial [abstract 10625]. J Clin Oncol 2011;29:. [Available online at: http://meetinglibrary. asco.org/content/83113-102; cited December 27, 2014]
82. Gluz O, Erber R, Kates R, et al. Predictive value of HER2, topoisomerase-ii (Topo-ii) and tissue inhibitor of metalloproteinases (timp-1) for efficacy of taxane-based chemotherapy in intermediate risk breast cancer-results from the ec-doc trial [abstract P1-06-03]. Presented as a poster at the 2011 San Antonio Breast Cancer Symposium; San Antonio, TX, U.S.A.; December 6-10, 2011. [Available online at: http://www.abstracts 2view.com/sabcs11/view.php?nu=SABCS11L_1495&terms; cited July 16, 2012]
83. Roche H, Fumoleau P, Spielmann M, et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for nodepositive breast cancer patients: the fnclcc pacs 01 trial. J Clin Oncol 2006;24:5664-71.
84. Coudert B, Campone M, Spielmann M, et al. Benefit of the sequential administration of docetaxel after standard fec regimen for node-positive breast cancer: long-term follow-up results of the fnclcc-pacs 01 trial [abstract 603]. Cancer Res 2009;69:.
85. Coudert B, Asselain B, Campone M, et al. Extended benefit from sequential administration of docetaxel after standard fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast cancer: the 8-year follow-up results of the unicancer-pacs01 trial. Oncologist 2012;17:900-9.
86. Penault-Llorca F, Andre F, Sagan C, et al. Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 2009;27:2809-15.
87. Jacquemier J, Boher JM, Roche H, et al. Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the fnclcc-pacs 01 randomized trial. Breast Cancer Res 2011;13:R109. [Available online at: http://breast-cancer-research.com/content/13/6/ R109; cited March 13, 2012]
88. Sakr H, Hamed RH, Anter AH, Yossef T. Sequential docetaxel as adjuvant chemotherapy for node-positive or/and T3 or T4 breast cancer: clinical outcome (Mansoura University). Med Oncol 2013;30:457.
89. Coombes RC, Bliss JM, Espie M, et al. Randomized, phase iii trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer. J Clin Oncol 2011;29:3247-54.
90. Albert JM, Buzdar AU, Guzman R, et al. Prospective randomized trial of 5-fluorouracil, doxorubicin, and cyclophosphamide (fac) versus paclitaxel and fac (tfac) in patients with operable breast cancer: impact of taxane chemotherapy on locoregional control. Breast Cancer Res Treat 2011;128:421-7.
91. Martin M, Pienkowski T, Mackey J, et al. on behalf of the Breast Cancer International Research Group 001 investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005;352:2302-13.
92. Mackey JR, Martin M, Pienkowski T, et al. on behalf of the trio/bcirg 001 investigators. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised bcirg 001 trial. Lancet Oncol 2013;14:72-80.
93. Hugh J, Hanson J, Cheang MC, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the bcirg 001 trial. J Clin Oncol 2009;27:1168-76.
94. Dumontet C, Krajewska M, Treilleux I, et al. bcirg 001 molecular analysis: prognostic factors in node-positive breast cancer patients receiving adjuvant chemotherapy. Clin Cancer Res 2010;16:3988-97.
95. Martin M, Segui MA, Anton A, et al. on behalf of the geicam 9805 investigators. Adjuvant docetaxel for high-risk, nodenegative breast cancer. N Engl J Med 2010;363:2200-10.
96. 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.
97. Sparano JA, O'Neill A, Gray RJ, et al. 10-Year update of E2197: phase iii doxorubicin/docetaxel (at) versus doxorubicin/ cyclophosphamide (ac) adjuvant treatment of ln+ and high-risk ln-breast cancer and the comparison of the prognostic utility of the 21-gene recurrence score (rs) with clinicopathologic features [abstract 1021]. J Clin Oncol 2012;30:. [Available online at: http://meetinglibrary.asco.org/content/94749-114; cited December 27, 2014]
98. Brain EG, Debled M, Eymard J, et al. Final results of the rapp-01 phase iii trial comparing doxorubicin and docetaxel with doxorubicin and cyclophosphamide in the adjuvant treatment of high-risk node negative and limited node positive (≤ 3) breast cancer patients [abstract 4101]. Cancer Res 2009;69(suppl):.
99. Del Mastro L, Costantini M, Durando A, et al. Cyclophosphamide, epirubicin, and 5-fluorouracil versus epirubicin plus paclitaxel in node-positive early breast cancer patients: a randomized, phase iii study of Gruppo Oncologico Nord Ovest-Mammella Intergruppo Group [abstract 516]. J Clin Oncol 2008;26:. [Available online at: http://meeting.ascopubs. org/cgi/content/abstract/26/15_suppl/516; cited December 27, 2014]
100. Roché H, Allouache D, Romieu G, et al. Five-year analysis of the fnclcc-pacs04 trial: fec100 vs ed75 for the adjuvant treatment of node positive breast cancer [abstract 602]. Cancer Res 2009;69(suppl):.
101. Gianni L, Baselga J, Eiermann W, et al. Phase iii trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol 2009;27:2474-81.
102. Zambetti M, Baselga J, Eiermann W, et al. Freedom from progression (ffp) by adding paclitaxel (t) to doxorubicin (a) followed by cmf as adjuvant or primary systemic therapy: 10-yr results of a randomized phase iii European Cooperative Trial in Operable Breast Cancer (ecto) [abstract 537]. J Clin Oncol 2013;31:. [Available online at: http://meetinglibrary.asco.org/ content/112868-132; cited December 28, 2014]
103. 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.
104. Shulman LN, Berry DA, Cirrincione CT, et al. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: calgb 40101 (Alliance). J Clin Oncol 2014;32:2311-17.
105. Shulman LN, Cirrincione CT, Berry DA, et al. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol 2012;30:4071-6.
106. Nitz U, Gluz O, Krepe H, et al. First interim toxicity analysis of the randomized phase iii wsg plan B trial comparing 4×ec-4×Doc versus 6×tc in breast cancer patients with HER2 negative breast cancer (bc) [abstract P5-18-03]. Cancer Res 2011;71(suppl):.
107. Ortmann U, Salmen J, Hepp PGM, et al. The success-c trial: interim analysis of toxicity evaluating the role of an anthracycline-free chemotherapy regimen in the adjuvant treatment of HER2/neu-negative breast cancer [abstract 1070]. J Clin Oncol 2011;29:. [Available online at: http://meetinglibrary.asco.org/ content/83477-102; cited December 28, 2014]
108. Mansi JL, Yellowlees A, Lipscombe J, et al. Five-year outcome for women randomised in a phase iii trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group study. Breast Cancer Res Treat 2010;122:787-94.
109. 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. [Erratum in: J Clin Oncol 2003;21:226]
110. Loesch D, Greco FA, Senzer NN, et al. Phase iii multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer. J Clin Oncol 2010;28:2958-65.
111. 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.
112. Swain SM, Jeong JH, Wolmark N. Amenorrhea from breast cancer therapy-not a matter of dose [letter]. N Engl J Med 2010;363:2268-70.
113. Ganz PA, Land SR, Geyer CE Jr, et al. Menstrual history and quality-of-life outcomes in women with node-positive breast cancer treated with adjuvant therapy on the nsabp B-30 trial. J Clin Oncol 2011;29:1110-16.
114. 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.
115. Poole CJ, Hiller L, Howard HC, et al. Tango: a randomized phase iii trial of gemcitabine (gem) in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy (ct) for women with early-stage breast cancer (ebc) [abstract 506]. J Clin Oncol 2008;26:. [Available online at: http://meeting.ascopubs.org/cgi/content/abstract/26/15_ suppl/506; cited December 29, 2014]
116. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008;358:1663-71. [Errata in: N Engl J Med 2008;359:106; and N Engl J Med 2009;360:1685]
117. Schneider BP, Zhao F, Wang M, et al. Neuropathy is not associated with clinical outcomes in patients receiving adjuvant taxane-containing therapy for operable breast cancer. J Clin Oncol 2012;30:3051-7.
118. Watanabe T, Kuranami M, Inoue K, et al. Phase iii two by two factorial comparison of doxorubicin and cyclophosphamide followed by a taxane vs. a taxane alone, and paclitaxel vs. docetaxel in operable node positive breast cancer-results of the first interim analysis of nsasbc02 trial [abstract 4103] Cancer Res 2009;69:. [Poster available at: http://www.csp. or.jp/cspor/company/results/N-SAS%20BC02poster%20 20081206.pdf; cited August 2012]
119. Shiroiwa T, Fukuda T, Shimozuma K, et al. Comparison of eq-5D scores among anthracycline-containing regimens followed by taxane and taxane-only regimens for node-positive breast cancer patients after surgery: the n-sas bc 02 trial. Value Health 2011;14:746-51.
120. Shimozuma K, Ohashi Y, Takeuchi A, et al. Taxane-induced peripheral neuropathy and health-related quality of life in postoperative breast cancer patients undergoing adjuvant chemotherapy: n-sas BC 02, a randomized clinical trial. Support Care Cancer 2012;20:3355-64.
121. Swain SM, Tang G, Geyer CE, et al. nsabp B-38: definitive analysis of a randomized adjuvant trial comparing dose-dense (dd) ac → paclitaxel (p) plus gemcitabine (g) with dd ac→p and with docetaxel, doxorubicin, and cyclophosphamide (tac) in women with operable, node-positive breast cancer [abstract LBA1000]. J Clin Oncol 2012;30:. [Available online at: http://meetinglibrary.asco.org/content/98794-114; cited December 29, 2014]
122. Swain SM, Tang G, Geyer CE Jr, et al. Definitive results of a phase iii adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the nsabp B-38 trial. J Clin Oncol 2013;31:3197-204.
123. Moebus V, Jackisch C, Lueck HJ, et al. 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 2010;28:2874-80.
124. Moebus V, Thomssen C, Lueck H, et al. Intense dose-dense (idd) sequential chemotherapy with epirubicin (e), paclitaxel (t), and cyclophosphamide (c) (etc) compared with conventionally scheduled chemotherapy in high-risk breast cancer patients (>3+ln): eight-year follow-up analysis [abstract 1018]. J Clin Oncol 2011;29:. [Available online at: http://meeting library.asco.org/content/81571-102; cited December 29, 2014]
125. Kelly CM, Green MC, Broglio K, et al. Phase iii trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol 2012;30:930-5.
126. Hofmann D, Nitz U, Gluz O, et al. wsg adapt-adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early breast cancer: study protocol for a prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase ii/iii trial. Trials 2013;14:261. [Available online at: http:// www.trialsjournal.com/content/14/1/261; cited July 16, 2014]
127. Untch M, von Minckwitz G, Konecny GE, et al. prepare trial: a randomized phase iii trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and cmf versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer-outcome on prognosis. Ann Oncol 2011;22:1999-2006.
128. Untch M, Fasching PA, Konecny GE, et al. on behalf of the Arbeitsgemeinschaft Gynäkologische Onkologie prepare investigators. prepare trial: a randomized phase iii trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and cmf versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer-results at the time of surgery. Ann Oncol 2011;22:1988-98.
129. Kaufmann M, Eiermann W, Schuette M, et al. Long-term results from the neoadjuvant GeparDuo trial: a randomized, multicenter, open phase iii study comparing a dose-intensified 8-week schedule of doxorubicin hydrochloride and docetaxel (adoc) with a sequential 24-week schedule of doxorubicin hydrochloride/cyclophosphamide followed by docetaxel (acdoc) regimen as preoperative therapy (nact) in patients (pts) with operable breast cancer (bc) [abstract 537]. J Clin Oncol 2010;28:. [Available online at: http://meetinglibrary.asco.org/ content/43877-74; cited December 29, 2014; poster also available at: http://www.germanbreastgroup.de/en/publications. html; cited July 6, 2012]
130. Darb-Esfahani S, Loibl S, Muller BM, et al. Identification of biology-based breast cancer types with distinct predictive and prognostic features: role of steroid hormone and HER2 receptor expression in patients treated with neoadjuvant anthracycline/ taxane-based chemotherapy. Breast Cancer Res 2009;11:R69.
131. Untch M, Mobus V, Kuhn W, et al. Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol 2009;27:2938-45.
132. Evans TRJ, Yellowlees A, Foster E, et al. Phase iii randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an Anglo-Celtic Cooperative Oncology Group study. J Clin Oncol 2005;23:2988-95.
133. von Minckwitz G, Blohmer JU, Costa SD, et al. Responseguided neoadjuvant chemotherapy for breast cancer. J Clin Oncol 2013;31:3623-30.
134. Von Minckwitz G, Schmitt WD, Loibl S, et al. Ki67 measured after neoadjuvant chemotherapy for primary breast cancer. Clin Cancer Res 2013;19:4521-31.
135. von Minckwitz G, Kummel S, Vogel P, et al. on behalf of the German Breast Group. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase iii randomized GeparTrio trial. J Natl Cancer Inst 2008;100:542-51.
136. von Minckwitz G, Kummel S, Vogel P, et al. on behalf of the German Breast Group. Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase iii randomized GeparTrio study. J Natl Cancer Inst 2008;100:552-62.
137. Members of the Breast Cancer Disease Site Group. Use of Bisphosphonates in Women with Breast Cancer. Evidencebased series 1-11. Ver. 2.2002. Toronto, ON: Cancer Care Ontario; 2012. [Available online at: https://www.cancercare. on.ca/common/pages/UserFile.aspx?fileId=34182; cited October 15, 2012]
138. Coleman R, Gnant M, Paterson A, et al. Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: a meta-analysis of individual patient data from randomised trials [abstract S4-07]. Cancer Res 2013;73(suppl):.
139. Cameron D, Brown J, Dent R, et al. Adjuvant bevacizumabcontaining therapy in triple-negative breast cancer (beatrice): primary results of a randomised, phase 3 trial. Lancet Oncol 2013;14:933-42.
140. Earl HM, Blenkinsop C, Grybowicz L, et al. artemis: randomized trial with neoadjuvant chemotherapy for patients with early breast cancer [abstract TPS1144]. J Clin Oncol 2012;30:. [Available online at: http://meetinglibrary.asco.org/ content/98025-114; cited December 29, 2014]
141. Earl HM, Hiller L, Blenkinsop C, et al. artemis: a randomised trial of bevacizumab with neoadjuvant chemotherapy (nact) for patients with HER2-negative early breast cancer-primary endpoint, pathological complete response (pcr) [abstract 1014]. J Clin Oncol 2014;32:. [Available online at: http://meeting library.asco.org/content/93667; cited December 29, 2014]
142. Parulekar W, Chen BE, Elliott C, et al. A phase iii randomized trial of metformin versus placebo on recurrence and survival in early-stage breast cancer (bc) (ncic Clinical Trials Group ma.32) [abstract TPS103]. J Clin Oncol 2011;29:. [Available online at: http://meetinglibrary.asco.org/content/82573-102; cited December 29, 2014]
143. Moore HCF, Unger JM, Phillips KA, et al. Phase iii trial (Prevention of Early Menopause Study [poems]-swog S0230) of lhrh analog during chemotherapy (ct) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: an international Intergroup trial of swog, ibcsg, ecog, and calgb (Alliance) [abstract LBA505]. J Clin Oncol 2014;32:. [Available online at: http://meetinglibrary.asco.org/ content/129172-144; cited December 29, 2014]
144. Mulcahy N. Practice changing: drug preserves fertility during chemo [online news article]. Medscape Multispecialty from WebMD; May 30, 2014. [Available online at: http://www. medscape.com/viewarticle/825989; cited July 21, 2014]
145. Mittendorf EA, Schneble EJ, Perez SA, et al. Primary analysis of the prospective, randomized, single-blinded phase ii trial of AE37 vaccine versus gm-csf alone administered in the adjuvant setting to high-risk breast cancer patients [abstract 638]. J Clin Oncol 2014;32:. [Available online at: http://meetinglibrary.asco.org/content/133001-144; cited December 29, 2014]
146. Vreeland TJ, Clifton GT, Hale DF, et al. Final results of the phase i/ii trials of the E75 adjuvant breast cancer vaccine [abstract P5-16-02]. Cancer Res 2012;72(suppl). [Available online at: http://cancerres.aacrjournals.org/content/72/24_ Supplement/P5-16-02; cited January 19, 2015]
147. Mittendorf EA, Clifton GT, Holmes JP, et al. Final report of the phase i/ii clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Ann Oncol 2014;25:1735-42.