Skip to main content

Adjuvant Biologic Agents for Breast Cancer

  • Chapter
  • First Online:
Breast Disease

Abstract

In the year 2013, a total of 234,580 new cases of breast cancer were diagnosed in the USA. Although the incidence of breast cancer is increasing, the 5-year survival rate has continued to improve. This improvement to overall survival (OS) is largely due to new chemotherapeutic and biologic agents. Biologic agents currently in use in early-stage breast cancer mainly target the human epidermal growth factor receptor 2 (HER2). HER2 belongs to the family of epidermal growth factor receptors (EGFRs) and is overexpressed in 20–30 % of all breast cancers. Further, the overexpression of HER2 is a negative prognostic and predictive factor. Patients with HER2+ breast cancers have more aggressive disease, a higher likelihood of lymph node involvement, decreased estrogen receptor (ER) expression, and increased resistance to endocrine therapy, while also found to have an increased responsiveness to anthracycline treatment. Initially approved by the Food and Drug Administration (FDA) in 1998 for treatment of HER2+ metastatic breast cancer, trastuzumab has been approved in the adjuvant setting after pivotal trials revealed a statistically significant reduction in the risk of recurrence by nearly 50 % and an improvement of overall survival (OS) by a third. Several other biologic agents are currently under investigation with the goal to improve the long-term survival in women with early-stage breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 189.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.

    Article  PubMed  Google Scholar 

  2. Reese DM, Slamon DJ. HER-2/neu signal transduction in human breast and ovarian cancer. Stem Cells. 1997;15:1–8.

    Article  CAS  PubMed  Google Scholar 

  3. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–12.

    Article  CAS  PubMed  Google Scholar 

  4. Pegram MD, Pauletti G, Slamon DJ. HER-2/neu as a predictive marker of response to breast cancer therapy. Breast Cancer Res Treat. 1998;52:65–77.

    Article  CAS  PubMed  Google Scholar 

  5. Seshadri R, Firgaira FA, Horsfall DJ, McCaul K, Setlur V, Kitchen P. Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group. J Clin Oncol. 1993;11:1936–42.

    CAS  PubMed  Google Scholar 

  6. Carlomagno C, Perrone F, Gallo C, De Laurentiis M, Lauria R, Morabito A, Pettinato G, Panico L, D’Antonio A, Bianco AR, De Placido S. c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases. J Clin Oncol. 1996;14:2702–8.

    CAS  PubMed  Google Scholar 

  7. Pietras RJ, Arboleda J, Reese DM, Wongvipat N, Pegram MD, Ramos L, Gorman CM, Parker MG, Sliwkowski MX, Slamon DJ. HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene. 1995;10:2435–46.

    CAS  PubMed  Google Scholar 

  8. Pritchard KI, Shepherd LE, O’Malley FP, Andrulis IL, Tu D, Bramwell VH, Levine MN. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 2006;354:2103–11.

    Article  CAS  PubMed  Google Scholar 

  9. Tetu B, Brisson J. Prognostic significance of HER-2/neu oncoprotein expression in node-positive breast cancer. The influence of the pattern of immunostaining and adjuvant therapy. Cancer. 1994;73:2359–65.

    Article  CAS  PubMed  Google Scholar 

  10. Tiwari RK, Borgen PI, Wong GY, Cordon-Cardo C, Osborne MP. HER-2/neu amplification and overexpression in primary human breast cancer is associated with early metastasis. Anticancer Res. 1992;12:419–25.

    CAS  PubMed  Google Scholar 

  11. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer Jr CE, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.

    Article  CAS  PubMed  Google Scholar 

  12. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365:1273–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, Rowland AM, Kotts C, Carver ME, Shepard HM. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A. 1992;89:4285–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Albanell J, Codony J, Rovira A, Mellado B, Gascon P. Mechanism of action of anti-HER2 monoclonal antibodies: scientific update on trastuzumab and 2C4. Adv Exp Med Biol. 2003;532:253–68.

    Article  CAS  PubMed  Google Scholar 

  15. Nahta R, Esteva FJ. Herceptin: mechanisms of action and resistance. Cancer Lett. 2006;232:123–38.

    Article  CAS  PubMed  Google Scholar 

  16. Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, Hortobagyi GN, Hung MC, Yu D. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004;6:117–27.

    Article  CAS  PubMed  Google Scholar 

  17. Henson ES, Hu X, Gibson SB. Herceptin sensitizes ErbB2-overexpressing cells to apoptosis by reducing antiapoptotic Mcl-1 expression. Clin Cancer Res. 2006;12:845–53.

    Article  CAS  PubMed  Google Scholar 

  18. Izumi Y, Xu L, di Tomaso E, Fukumura D, Jain RK. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature. 2002;416:279–80.

    Article  CAS  PubMed  Google Scholar 

  19. Cooley S, Burns LJ, Repka T, Miller JS. Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu. Exp Hematol. 1999;27:1533–41.

    Article  CAS  PubMed  Google Scholar 

  20. Perez EA, Press MF, Dueck AC, Jenkins RB, Kim C, Chen B, Villalobos I, Paik S, Buyse M, Wiktor AE, Meyer R, Finnigan M, Zujewski J, Shing M, Stern HM, Lingle WL, Reinholz MM, Slamon DJ. Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005). Breast Cancer Res Treat. 2013;138:99–108.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF. 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. 2007;25:118–45.

    Article  CAS  PubMed  Google Scholar 

  22. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:719–26.

    Article  CAS  PubMed  Google Scholar 

  23. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.

    Article  CAS  PubMed  Google Scholar 

  24. Pegram MD, Lopez A, Konecny G, Slamon DJ. Trastuzumab and chemotherapeutics: drug interactions and synergies. Semin Oncol. 2000;27:21–5.

    CAS  PubMed  Google Scholar 

  25. Pegram MD, Konecny GE, O’Callaghan C, Beryt M, Pietras R, Slamon DJ. Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Natl Cancer Inst. 2004;96:739–49.

    Article  CAS  PubMed  Google Scholar 

  26. Esteva FJ, Valero V, Booser D, Guerra LT, Murray JL, Pusztai L, Cristofanilli M, Arun B, Esmaeli B, Fritsche HA, Sneige N, Smith TL, Hortobagyi GN. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:1800–8.

    Article  CAS  PubMed  Google Scholar 

  27. Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Anton A, Lluch A, Kennedy J, O’Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005;23:4265–74.

    Article  CAS  PubMed  Google Scholar 

  28. Nabholtz JM, Gligorov J. Docetaxel/trastuzumab combination therapy for the treatment of breast cancer. Expert Opin Pharmacother. 2005;6:1555–64.

    Article  CAS  PubMed  Google Scholar 

  29. Schaller G, Fuchs I, Gonsch T, Weber J, Kleine-Tebbe A, Klare P, Hindenburg HJ, Lakner V, Hinke A, Bangemann N. Phase II study of capecitabine plus trastuzumab in human epidermal growth factor receptor 2 overexpressing metastatic breast cancer pretreated with anthracyclines or taxanes. J Clin Oncol. 2007;25:3246–50.

    Article  CAS  PubMed  Google Scholar 

  30. Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, Flynn PJ, Mailliard JA, Kardinal CG, Krook JE, Thrower AR, Visscher DW, Jenkins RB. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005;6:425–32.

    Article  CAS  PubMed  Google Scholar 

  31. Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006;24:2786–92.

    Article  CAS  PubMed  Google Scholar 

  32. Bendell JC, Domchek SM, Burstein HJ, Harris L, Younger J, Kuter I, Bunnell C, Rue M, Gelman R, Winer E. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972–7.

    Article  PubMed  Google Scholar 

  33. Burstein HJ, Lieberman G, Slamon DJ, Winer EP, Klein P. Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy. Ann Oncol. 2005;16:1772–7.

    Article  CAS  PubMed  Google Scholar 

  34. Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011;29:4491–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Romond E, Suman VJ, Jeong J-H, Sledge Jr GW, Geyer CE, Martino S, Rastogi P, Gralow JR, Swain SM, Winer E, Colon-Otero G, Hudis C, Paik S, Davidson NE, Mamounas EP, Zujewski JA, Wolmark N, Perez EA. S5-5 Trastuzumab plus adjuvant chemotherapy for HER2-positive breast cancer: Final planned joint analysis of overall survival (OS) from NSABP B-31 and NCCTG N9831. Cancer Res. 2012;72(24 Suppl):105s.

    Google Scholar 

  36. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.

    Article  CAS  PubMed  Google Scholar 

  37. Goldhirsch A, Piccart-Gebhart M, Procter M, de Azambuja E, Weber HA, Untch M, Smith I, Gianni L, Jackisch C, Cameron D, Bell R, Dowsett M, Gelber RD, Leyland-Jones B, Baselga J. S5-2. HERA TRIAL: 2 years versus 1 year of trastuzumab after adjuvant chemotherapy in women with HER2-positive early breast cancer at 8 years of median follow up. Cancer Res. 2013;72(24 suppl):103s.

    Google Scholar 

  38. Spielmann M, Roche H, Delozier T, Canon JL, Romieu G, Bourgeois H, Extra JM, Serin D, Kerbrat P, Machiels JP, Lortholary A, Orfeuvre H, Campone M, Hardy-Bessard AC, Coudert B, Maerevoet M, Piot G, Kramar A, Martin AL, Penault-Llorca F. Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol. 2009;27:6129–34.

    Article  CAS  PubMed  Google Scholar 

  39. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkio S, Flander M, Helle L, Ingalsuo S, Johansson K, Jaaskelainen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354:809–20.

    Article  CAS  PubMed  Google Scholar 

  40. Pivot X, Romieu G, Bonnefoi H, Pierga J-Y, Kerbrat P, Guastalla J-P, Lortholary A, Espie M, Fumoleau P, Khayat D, Pauporte I, Kramar A. S5-3. PHARE Trial results of subset analysis comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer. Cancer Res. 2013;72(24 suppl):105s.

    Google Scholar 

  41. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gomez H, Dinh P, Fauria K, van Dooren V, Goldhirsch G, Chang TW, Horvath Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sonz JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379:633–40.

    Article  CAS  PubMed  Google Scholar 

  42. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–43.

    Article  CAS  PubMed  Google Scholar 

  43. Gomez HL, Doval DC, Chavez MA, Ang PC, Aziz Z, Nag S, Ng C, Franco SX, Chow LW, Arbushites MC, Casey MA, Berger MS, Stein SH, Sledge GW. Efficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancer. J Clin Oncol. 2008;26:2999–3005.

    Article  CAS  PubMed  Google Scholar 

  44. Johnston S, Pippen Jr J, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O’Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009;27:5538–46.

    Article  CAS  PubMed  Google Scholar 

  45. Zhou Y, Li S, Hu YP, Wang J, Hauser J, Conway AN, Vinci MA, Humphrey L, Zborowska E, Willson JK, Brattain MG. Blockade of EGFR and ErbB2 by the novel dual EGFR and ErbB2 tyrosine kinase inhibitor GW572016 sensitizes human colon carcinoma GEO cells to apoptosis. Cancer Res. 2006;66:404–11.

    Article  CAS  PubMed  Google Scholar 

  46. Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, Hilfrich J, Strumberg D, Fasching PA, Kreienberg R, Tesch H, Hanusch C, Gerber B, Rezai M, Jackisch C, Huober J, Kuhn T, Nekljudova V, von Minckwitz G. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012;13:135–44.

    Article  CAS  PubMed  Google Scholar 

  47. Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007;13:228–33.

    Article  CAS  PubMed  Google Scholar 

  48. Burris III HA, Hurwitz HI, Dees EC, Dowlati A, Blackwell KL, O’Neil B, Marcom PK, Ellis MJ, Overmoyer B, Jones SF, Harris JL, Smith DA, Koch KM, Stead A, Mangum S, Spector NL. Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J Clin Oncol. 2005;23:5305–13.

    Article  CAS  PubMed  Google Scholar 

  49. Kaklamani VG, Siziopikou K, Scholtens D, Lacouture M, Gordon J, Uthe R, Meservey C, Hansen N, Khan SA, Jeruss JS, Bethke K, Cianfrocca M, Rosen S, Von Roenn J, Wayne J, Parimi V, Jovanovic B, Gradishar W. Pilot neoadjuvant trial in HER2 positive breast cancer with combination of nab-paclitaxel and lapatinib. Breast Cancer Res Treat. 2011;132:833–42.

    Article  PubMed  Google Scholar 

  50. Perez EA, Koehler M, Byrne J, Preston AJ, Rappold E, Ewer MS. Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin Proc. 2008;83:679–86.

    Article  PubMed  Google Scholar 

  51. ALTTO (Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation) Study; BIG 2-06/N063D. 2013. http://www.cancer.gov/clinicaltrials/search/view?cdrid=558836&version=healthprofessional.

  52. Goss PE, Smith IE, O’Shaughnessy J, Ejlertsen B, Kaufmann M, Boyle F, Buzdar AU, Fumoleau P, Gradishar W, Martin M, Moy B, Piccart-Gebhart M, Pritchard KI, Lindquist D, Chavarri-Guerra Y, Aktan G, Rappold E, Williams LS, Finkelstein DM. Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14:88–96.

    Article  CAS  PubMed  Google Scholar 

  53. Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109–19.

    Article  CAS  PubMed  Google Scholar 

  54. Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. 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.

    Article  CAS  PubMed  Google Scholar 

  55. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–76.

    Article  CAS  PubMed  Google Scholar 

  56. Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O’Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011;29:1252–60.

    Article  CAS  PubMed  Google Scholar 

  57. Cameron D, Brown J, Dent R, Jackisch C, Mackey J, Pivot X, Steger G, Suter T, Toi M, Parmar M, Bubuteishvili-Pacaud L, Henschel V, Laeufle R, Bell R. S6-5. Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple-negative breast cancer. Cancer Res. 2013;72(24 Supp):55s.

    Google Scholar 

  58. NCCN Clinical practice guidelines in Oncology. NCCN, 2008. http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Virginia G. Kaklamani MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kaklamani, V.G., Gradishar, W.J. (2015). Adjuvant Biologic Agents for Breast Cancer. In: Riker, A. (eds) Breast Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1145-5_25

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1145-5_25

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-1144-8

  • Online ISBN: 978-1-4939-1145-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics