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Breast Disease pp 223-238 | Cite as

Preoperative Therapy for Operable Breast Cancer

  • Yesim Eralp
Chapter

Abstract

Preoperative systemic chemotherapy (PSC), also known as “neoadjuvant chemotherapy,” is an important therapy option for most patients with breast cancer. PSC has evolved as an integral part of the multidisciplinary treatment approach for breast cancer and has a long history that dates back nearly four decades. Despite previous beliefs that it is more suitable for locally advanced or inflammatory disease, PSC is becoming increasingly popular in the breast oncology community for the treatment of earlier-stage disease. As safe and effective as adjuvant chemotherapy, this approach not only has the advantage of facilitating breast-conserving surgery (BCS) for patients in whom an optimal cosmetic outcome with upfront surgery is not possible but also has the potential to improve drug delivery to the tumor site by retaining intact vasculature before any local intervention is made. Furthermore, PSC provides an ideal setting in which the responsiveness of a given treatment can be observed and provides relevant information on the biology of the tumor by enabling biomarker analysis. Accumulating data on the strong association with survival and pathological complete response (pCR) may lead to a change in the regulatory requirements for drug approval and, consequently, reduce the need for costly and time-consuming large adjuvant trials.

In conclusion, PSC is a valuable research tool for identifying predictive molecular biomarkers and a valid treatment option for patients with early-stage breast cancer. However, the decision to treat a patient with neoadjuvant chemotherapy requires careful clinical judgment and multidisciplinary evaluation by an experienced team.

Keywords

Neoadjuvant treatment for breast cancer  Chemotherapy  Biological agents  PARP inhibitors  Dual Her-2 blockade  Immune checkpoint inhibitors  Pathological complete response  Response-guided treatment 

References

  1. 1.
    Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.CrossRefGoogle Scholar
  2. 2.
    van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L, et al. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224–37.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006;24:2019–27.CrossRefGoogle Scholar
  4. 4.
    Gianni L, Baselga J, Eiermann W, Porta VG, Semiglazov V, Lluch A, 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Untch M, Mobus V, Kuhn W, Muck BR, Thomssen C, Bauerfeind I, et al. Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol. 2009;27:2938–45.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16:2672–85.CrossRefGoogle Scholar
  9. 9.
    Pierga JY, Mouret E, Diéras V, Laurence V, Beuzeboc P, Dorval T, et al. Prognostic value of persistent node involvement after neoadjuvant chemotherapy in patients with operable breast cancer. Br J Cancer. 2000;83(11):1480–7.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003;12(5):320–7.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–804.CrossRefGoogle Scholar
  12. 12.
    Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol. 2002;20(6):1456–66.CrossRefGoogle Scholar
  13. 13.
    Untch M, Möbus V, Kuhn W, Muck BR, Thomssen C, Bauerfeind I, Harbeck N, Werner C, Lebeau A, Schneeweiss A, Kahlert S, von Koch F, Petry KU, Wallwiener D, Kreienberg R, Albert US, Lück HJ, Hinke A, Jänicke F, Konecny GE. Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol. 2009;27(18):2938–45.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Frasci G, D’Aiuto G, Comella P, D’Aiuto M, Di Bonito M, Ruffolo P, et al. Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908. Ann Oncol. 2010;21:707–16.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, 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): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014;15:640–7.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Evans TR, Yellowlees A, Foster E, Earl H, Cameron DA, Hutcheon AW, 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(13):2988–95.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Buzdar AU, Singletary SE, Theriault RL, Booser DJ, Valero V, Ibrahim N, et al. Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol. 1999;17:3412–7.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Baldini E, Gardin G, Giannessi PG, Evangelista G, Roncella M, Prochilo T, et al. Accelerated versus standard cyclophosphamide, epirubicin and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil: a randomized phase III trial in locally advanced breast cancer. Ann Oncol. 2003;14:227–32.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Smith IE, A’Hern RP, Coombes GA, Howell A, Ebbs SR, Hickish TF, et al. TOPIC Trial Group. A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neoadjuvant treatment of early breast cancer: 5 year results of the TOPIC trial. Ann Oncol. 2004;15:751–8.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Chua S, Smith IE, A’Hern RP, Coombes GA, Hickish TF, Robinson AC, et al. TOPIC Trial Group. Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2). Ann Oncol. 2005;16:1435–41.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    von Minckwitz G, Untch M, Nüesch E, Loibl S, Kaufmann M, Kümmel S, 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(1):145–56.CrossRefGoogle Scholar
  22. 22.
    Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. P athological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.CrossRefGoogle Scholar
  23. 23.
    Ring AE, Smith IE, Ashley S, Fulford LG, Lakhani SR. Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer. Br J Cancer. 2004;91(12):2012–7.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Fisher ER, Wang J, Bryant J, Fisher B, Mamounas E, Wolmark N. Pathobiology of preoperative chemotherapy: findings from the National Surgical Adjuvant Breast and Bowel (NSABP) protocol B-18. Cancer. 2002;95(4):681–95.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, et al. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24(7):1037–44.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Esserman LJ, Berry DA, DeMichele A, Yau C, Perou CM, Carey L, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012;30(26):3242–9.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Ignatiadis M, Singhal SK, Desmedt C, Haibe-Kains B, Criscitiello C, Andre F, et al. Gene modules and response to neoadjuvant chemotherapy in breast cancer subtypes: a pooled analysis. J Clin Oncol. 2012;30(16):1996–2004.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278–84.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    von Minckwitz G, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, 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(12):2015–23.CrossRefGoogle Scholar
  30. 30.
    Prat A, De Angelis C, Pascual T, Gutierrez C, Llombart-Cussac A, Wang T, et al. HER2-enriched subtype and ERBB2 mRNA as predictors of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer: a combined analysis of TBCRC006/023 and PAMELA trials. J Clin Oncol. 2018;36 (suppl; abstr 509).CrossRefGoogle Scholar
  31. 31.
    Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, Carey L, et al. I-SPY 1 TRIAL Investigators. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat. 2012;132(3):1049–62.PubMedCrossRefGoogle Scholar
  32. 32.
    von Minckwitz G, Blohmer JU, Costa S, Denkert C, Eidtmann H, Eiermann W, et al. Response guided neoadjuvant chemotherapy for breast cancer – results of the GeparTrio Trial. J Clin Oncol. 2013;31:3623–30.CrossRefGoogle Scholar
  33. 33.
    von Minckwitz G, Schneeweiss A, Loibl S, Salat CT, Rezai M, Zahm DM et al. Early survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). SABCS. 8-12 Dec 2015; abstr S2-04.Google Scholar
  34. 34.
    Cohen I, Blasberg R. Impact of the tumor microenvironment on tumor-infiltrating lymphocytes: focus on breast cancer. Breast Cancer Basic Clin Res. 2017;11:1–12.CrossRefGoogle Scholar
  35. 35.
    Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25(28):4414–22.CrossRefGoogle Scholar
  36. 36.
    Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, et al. Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol. 2017;35(10):1049–60.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Sheri A, Smith IE, Johnston SR, A’Hern R, Nerurkar A, Jones RL, et al. Residual proliferative cancer burden to predict long-term outcome following neoadjuvant chemotherapy. Ann Oncol. 2015;26(1):75–80.PubMedCrossRefGoogle Scholar
  38. 38.
    Symmans WF, Yau C, Chen Y, Datnow B, Wei S, Feldman MD, et al. Residual cancer burden (RCB) as prognostic in the I-SPY 2 TRIAL. J Clin Oncol. 2018;36 (suppl; abstr 520).CrossRefGoogle Scholar
  39. 39.
    Thomas E, Holmes FA, Smith TL, Buzdar AU, Frye DK, Fraschini G, et al. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol. 2004;22(12):2294–302.PubMedCrossRefGoogle Scholar
  40. 40.
    von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, et al; 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(8):542–51.CrossRefGoogle Scholar
  41. 41.
    Gebhart G, Gámez C, Holmes E, Robles J, Garcia C, Cortés M, et al. 18F-FDG PET/CT for early prediction of response to neoadjuvant lapatinib, trastuzumab, and their combination in HER2-positive breast cancer: results from Neo-ALTTO. J Nucl Med. 2013;54(11):1862–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Connolly RM, Leal JP, Solnes L, Huang C, Carpenter A, Gaffney K, et al. TBCRC026: phase II clinical trial assessing the correlation of standardized uptake value (SUV) on positron emission tomography (PET) with pathological complete response (pCR) to pertuzumab and trastuzumab in patients with primary operable HER2-positive breast cancer. J Clin Oncol. 2018;36 (suppl; abstr 511).CrossRefGoogle Scholar
  43. 43.
    Prat A, Castan JC, Pare L, Galvan P, Bermejo B, Martínez N, Vidal M, et al. PAM50 intrinsic subtype as a predictor of pathological complete response following neoadjuvant dual HER2 blockade without chemotherapy in HER2-positive breast cancer: first results of the PAMELA clinical trial. Cancer Res. 2017;77(4 Supplement):S3–03.Google Scholar
  44. 44.
    Balko JM, Cook RS, Vaught DB, Kuba MG, Miller TW, Bhola NE, et al. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Nat Med. 2012;18(7):1052–9.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Gao Q, Patani N, Dunbier AK, Ghazoui Z, Zvelebil M, Martin LA, Dowsett M. Effect of aromatase inhibition on functional gene modules in estrogen receptor-positive breast cancer and their relationship with antiproliferative response. Clin Cancer Res. 2014;20(9):2485–94.PubMedCrossRefGoogle Scholar
  46. 46.
    De Lena M, Zucali R, Viganotti G, Valagussa P, Bonadonna G. Combined chemotherapy-radiotherapy approach in locally advanced (T3b–T4) breast cancer. Cancer Chemother Pharmacol. 1978;1:53–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27–39.CrossRefGoogle Scholar
  48. 48.
    Therasse P, Mauriac L, Welnicka-Jaskiewicz M, Bruning P, Cufer T, Bonnefoi H, et al. EORTC. Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study. J Clin Oncol. 2003;21(5):843–50.PubMedCrossRefGoogle Scholar
  49. 49.
    Romieu G, Tubiana-Hulin M, Fumoleau P, Namer M, Delva R, et al. A multicenter randomized phase II study of 4 or6 cycles of adriamycin/Taxol (paclitaxel) (AT) as neoadjuvant treatment of breast cancer (BC). Ann Oncol. 2002;13(Suppl 5):33–9.CrossRefGoogle Scholar
  50. 50.
    Diéras V, Fumoleau P, Romieu G, Tubiana-Hulin M, Namer M, Mauriac L, et al. Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer. J Clin Oncol. 2004;22(24):4958–65.PubMedCrossRefGoogle Scholar
  51. 51.
    Steger GG, Kubista E, Hausmaninger H, Gnant M, Tausch C, Lang A, et al. 6 vs. 3 cycles of epirubicin/docetaxel + G-CSF in operable breast cancer: results of ABCSG-14 [abstract]. 2004;22(July 15 Suppl 14S):A553.Google Scholar
  52. 52.
    Han S, Kim J, Lee J, Chang E, Gwak G, Cho H, et al. Comparison of 6 cycles versus 4 cycles of neoadjuvant epirubicin plus docetaxel chemotherapy in stages II and III breast cancer. Eur J Surg Oncol. 2009;35(6):583–7.PubMedCrossRefGoogle Scholar
  53. 53.
    von Minckwitz G, Raab G, Caputo A, Schütte M, Hilfrich J, Blohmer JU, et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005;23:2676–85.CrossRefGoogle Scholar
  54. 54.
    Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, et al. On behalf of; 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 with or without darbepoetin alfa in primary breast cancer--outcome on prognosis. Ann Oncol. 2011;22(9):1999–2006.PubMedCrossRefGoogle Scholar
  55. 55.
    Steger GG, Greil R, Jakesz R, Lang A, Mineritsch B, Melbinger-Zeinitzer E, 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(24 Suppl):564s (abstract 1081).Google Scholar
  56. 56.
    Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366(4):310–20.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Li Q, Jiang Y, Wei W, Yang H, Liu J. Clinical efficacy of including capecitabine in neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2013;8(1):e53403.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Earl HM, Vallier A, Hiller L, Fenwick N, Young J, Iddawela M, et al. 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 2x2 factorial randomized phase III trial. Lancet. 2014;15(2):201–12.PubMedCrossRefGoogle Scholar
  59. 59.
    Snider JN, Schwartzberg L, Young RR, Yunus F, Allen JW, Verrier C, et al. Pathologic complete response with weekly nanoparticle albumin bound paclitaxel plus carboplatin followed by doxorubicin plus cyclophosphamide with concurrent bevacizumab for triple negative breast cancer. J Clin Oncol (meeting abstracts). 2013;31 (Suppl.) (abstract 1068).Google Scholar
  60. 60.
    Mrozek E, Lustber MB, Knopp MV, Spigos DG, Yang X, Houton LA, et al. Phase II trial of neoadjuvant chemotherapy with weekly nanoparticle albumin bound paclitaxel, carboplatin and bevacizumab in women with clinical stages II-III breast cancer: pathologic response prediction by changes in angiogenic volüme by dynamic contrast enhanced magnetic resonance imaging. J Clin Oncol (meeting abstracts). 2010;28 (Suppl.) (abstract 604).Google Scholar
  61. 61.
    Sinclair NF, Abu-Khalaf MM, Rizack T, Rosati K, Chung G, Legare RD, et al. Neoadjuvant weekly nanoparticle albumin bound paclitaxel, carboplatin plus bevacizumab with or without dose-dense doxorubicin-cyclophosphamide plus B in ER+/Her-2 negative and triple negative breast cancer: a BrUOG study. J Clin Oncol (meeting abstracts). 2012;30 (Suppl.) (abstract 1045).Google Scholar
  62. 62.
    Untch M, Jackisch C, Schneeweiß A, Conrad B, Aktas B, Denkert C, et al. Nanoparticle-based paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy with weekly for early breast cancer (GeparSepto-GBG 69): a randomized phase III trial. Lancet Oncol. 2016;17(3):345–56.CrossRefGoogle Scholar
  63. 63.
    von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15(7):747–56.CrossRefGoogle Scholar
  64. 64.
    Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015;33(1):13–21.CrossRefGoogle Scholar
  65. 65.
    Alba E, Chacon JI, Lluch A, Anton A, Estevez L, Cirauqui B, et al. A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study. Breast Cancer Res Treat. 2012;136(2):487–93.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione C, Tolaney S, et al. Event-free and overall survival following neoadjuvant weekly paclitaxel and dose -dense AC +/− carboplatin and/or bevacizumab in triple-negative breast cancer: outcomes from CALGB 40603 (Alliance) 38th Annual SABCS. 8-12 Dec 2015; Abstract S2-05.Google Scholar
  67. 67.
    Gluz O, Nitz U, Liedtke C, Christgen M, Grischke EM, Forstbauer H, et al. Comparison of Neoadjuvant Nab-Paclitaxel+Carboplatin vs Nab Paclitaxel+Gemcitabine in triple-negative breast cancer: randomized WSG-ADAPT-TN trial results. J Natl Cancer Inst. 2017;110(6):628–37.CrossRefGoogle Scholar
  68. 68.
    Telli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC, et al. Homologous Recombination Deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin Cancer Res. 2016;22(15):3764–73.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Telli ML, Metzger O, Timms K, Evans B, Vogel D, Wei H, et al. Evaluation of homologous recombination deficiency (HRD) status with pathological response to carboplatin +/− veliparib in BrighTNess, a randomized phase 3 study in early stage TNBC. J Clin Oncol. 2018;36 (suppl; abstr 519).CrossRefGoogle Scholar
  70. 70.
    Arun B, Bayraktar S, Liu DD, Gutierrez Barrera AM, Atchley D, Pusztai L, et al. Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience. J Clin Oncol. 2011;29(28):3739–46.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Hurvitz SA, Miller JM, Dichman R, Perez AT, Patel R, Zehngebot LM, et al. Final analysis of a phase II 3-arm randomized trial of neoadjuvant trastuzumab or lapatinib or the combination of trastuzumab and lapatinib, followed by six cycles of docetaxel and carboplatin with trastuzumab and/or lapatinib in patients with HER2 breast cancer (TRIO-US B07) [SABCS abstract S1-S2]. Cancer Res. 2013;73(24 suppl).Google Scholar
  72. 72.
    Van Ramshorst MS, van Werkhoven E, Mandjes IA, Kemper I, Dezentje VO, Oving IM, et al. A phase III trial of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2+ breast cancer: the TRAIN-2 study (BOOG 2012-03). ASCO 2017 Annual Meeting Chicago, IL. June 2-6, 2017. J Clin Oncol. 35(15-suppl):abs 507.Google Scholar
  73. 73.
    Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115–26.CrossRefGoogle Scholar
  74. 74.
    Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, 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.PubMedCrossRefGoogle Scholar
  75. 75.
    Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010;28(12):2024–31.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, et al. Arbeitsgemeinschaft Gynäkologische Onkologie-Breast (AGO-B) Study Group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012;13(2):135–44.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C. et al; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379(9816):633–40.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, et al. Molecular heterogeneity and response to Neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus Trastuzumab with or without Lapatinib. J Clin Oncol. 2016;34(6):542–9.PubMedCrossRefGoogle Scholar
  79. 79.
    Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, et al. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14(12):1183–92.PubMedCrossRefGoogle Scholar
  80. 80.
    Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, 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(1):25–32.CrossRefGoogle Scholar
  81. 81.
    Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;17(6):791–800.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    DeMichele AM, Moulder S, Meredith B, Yee D, Wallace A, Chien J et al. Efficacy of T-DM1+pertuzumab over standard therapy for HER2+ breast cancer: results from the neoadjuvant I-SPY 2 TRIAL. AACR Annual Meeting April 16–20, 2016; CT042.Google Scholar
  83. 83.
    Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, et al. Trastuzumab Emtansine with or without Pertuzumab versus Trastuzumab plus Taxane for human epidermal growth factor receptor 2-positive, advanced breast Cancer: primary results from the phase III MARIANNE Study. J Clin Oncol. 2017;35(2):141–8.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Guarneri V, Frassoldati A, Bottini A, Cagossi K, Bisagni G, Sarti S, et al. Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol. 2012;30(16):1989–95.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Jacobs SA, Robidoux A, Garcia JMP, Abraham J, La Verde N, Orcutt J.M et al. NSABP FB-7: a phase II randomized trial evaluating neoadjuvant therapy with weekly paclitaxel (P) plus neratinib (N) or trastuzumab (T) or neratinib and trastuzumab (N+T) followed by doxorubicin and cyclophosphamide (AC) with postoperative T in women with locally advanced HER2-positive breast cancer. Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX; PD5-04.Google Scholar
  86. 86.
    von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, et al. German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366(4):299–309.CrossRefGoogle Scholar
  87. 87.
    Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, et al. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015;16(9):1037–48.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Huober J, Fasching PA, Hanusch C, Rezai M, Eidtmann H, Kittel K, et al. Neoadjuvant chemotherapy with paclitaxel and everolimus in breast cancer patients with non-responsive tumours to epirubicin/cyclophosphamide (EC) ± bevacizumab- results of the randomised GeparQuinto study (GBG 44). Eur J Cancer. 2013;49(10):2284–93.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res. 2011;17(5):1082–9.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, et al. Consortium of Investigators of Modifiers of BRCA1/2. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prev. 2012;21(1):134–47.CrossRefGoogle Scholar
  91. 91.
    Sharma P, Klemp JR, Kimler BF, Mahnken JD, Geier LJ, Khan QJ, et al. Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing. Breast Cancer Res Treat. 2014;145(3):707–14.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol. 2015;33(4):304–11.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Rugo HS, Olopade OI, DeMichele A, Yau C, van’t Veer LJ, Buxton MB, et al. I-SPY 2 Investigators. Adaptive randomization of Veliparib-Carboplatin treatment in breast cancer. N Engl J Med. 2016;375(1):23–34.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Loibl S, O’Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): arandomised, phase 3 trial. Lancet Oncol. 2018;19(4):497–509.CrossRefGoogle Scholar
  95. 95.
    Litton JK, Scoggins M, Hess KR, Adrada B, Barcenas CH, Murthy RK, et al. Neoadjuvant talazoparib (TALA) for operable breast cancer patients with a BRCA mutation (BRCA+). J Clin Oncol. 2018;36 (suppl; abstr 508).CrossRefGoogle Scholar
  96. 96.
    Bianchini G, Qi Y, Alvarez RH, Iwamoto T, Coutant C, Ibrahim NK, et al. Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers. J Clin Oncol. 2010;28(28):4316–23.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Salgado R, Denkert C, Campbell C, Savas P, Nuciforo P, Aura C, et al. Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO trial. JAMA Oncol. 2015;1(4):448–54.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Issa-Nummer Y, Darb-Esfahani S, Loibl S, Kunz G, Nekljudova V, Schrader I, et al. Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial. PLoS One. 2013;8(12):e79775.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014;25(8):1544–50.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015;33(9):983–91.CrossRefGoogle Scholar
  101. 101.
    Luen S, Virassamy B, Savas P, Salgado R, Loi S. The genomic landscape of breast cancer and its interaction with host immunity. Breast. 2016;29:241–50.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Carbognin L, Pilotto S, Nortilli R, Brunelli M, Nottegar A, Sperduti I, et al. Predictive and prognostic role of tumor-infiltrating lymphocytes for early breast cancer according to disease subtypes: sensitivity analysis of randomized trials in adjuvant and neoadjuvant setting. Oncologist. 2016;21(3):283–91.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Muenst S, Soysal SD, Gao F, Obermann EC, Oertli D, Gillanders WE. The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2013;139(3):667–76.PubMedCrossRefGoogle Scholar
  104. 104.
    Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016;34(21):2460–7.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, et al. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. J Clin Oncol. 2017;35(15_suppl):1008.CrossRefGoogle Scholar
  106. 106.
    Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat. 2018;167(3):671–86.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Schmid P, Cruz C, Braiteh FS. Atezolizumab in metastatic TNBC (mTNBC): long-term clinical outcomes and biomarker analyses. 2017 AACR Annual Meeting. Abstract 2986, 2017.Google Scholar
  108. 108.
    Rugo HS, Delord JP, Im SA, Ott PA, Piha-Paul SA, Bedard PL, et al. Safety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Clin Cancer Res. 2018;24(12):2804–11.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Nanda R, Liu MC, Yau C, Asare S, Hylton N, Van’t Veer L, et al. Pembrolizumab plus standard neoadjuvant therapy for high-risk breast cancer (BC): results from I-SPY 2. J Clin Oncol. 2017;35(15_suppl):506.CrossRefGoogle Scholar
  110. 110.
    Schmid P, Park YH, Muñoz-Couselo E, Kim SB, Sohn J, Im SA, et al. Pembrolizumab (pembro) + chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): preliminary results from KEYNOTE-173. J Clin Oncol. 2017;35(15_suppl):556.CrossRefGoogle Scholar
  111. 111.
    Loibl S, Untch M, Burchardi N, Huober JB, Blohmer JU, Grischke EM, et al. Randomized phase II neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (TNBC). J Clin Oncol. 2018;36 (suppl; abstr 104).CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Yesim Eralp
    • 1
  1. 1.Department of Medical OncologyIstanbul University Institute of OncologyTopkapi, IstanbulTurkey

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