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Primary Systemic Therapy for Breast Cancer

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Breast Cancer Management for Surgeons

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Abstract

Primary systemic chemotherapy serves several purposes. While reducing tumour volume and either rendering inoperable tumours operable or larger tumours suitable for breast-conserving therapy, it also allows in vivo monitoring of tumour response. Therefore, primary systemic chemotherapy should be considered in cases where the need for chemotherapy is apparent at the time of diagnoses. Different schedules are available for distinct breast cancer subtypes. Ongoing clinical trials for primary systemic chemotherapy are introducing novel agents, scheduling protocols and translational analyses.

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References

  1. Fisher B, Slack N, Katrych D, Wolmark N. Ten year follow-up results of patients with carcinoma of the breast in a co-operative clinical trial evaluating surgical adjuvant chemotherapy. Surg Gynecol Obstet. 1975;140(4):528–34.

    CAS  PubMed  Google Scholar 

  2. Bonadonna G, Brusamolino E, Valagussa P, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976;294(8):405–10.

    Article  CAS  PubMed  Google Scholar 

  3. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.

    Article  Google Scholar 

  4. Corbett TH, Griswold DP Jr, Roberts BJ, Peckham JC, Schabel FM Jr. Biology and therapeutic response of a mouse mammary adenocarcinoma (16/C) and its potential as a model for surgical adjuvant chemotherapy. Cancer Treat Rep. 1978;62(10):1471–88.

    CAS  PubMed  Google Scholar 

  5. Ezzat AA, Ibrahim EM, Ajarim DS, et al. High complete pathological response in locally advanced breast cancer using paclitaxel and cisplatin. Breast Cancer Res Treat. 2000;62(3):237–44.

    Article  CAS  PubMed  Google Scholar 

  6. Schwartz GF, Birchansky CA, Komarnicky LT, et al. Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast. Cancer. 1994;73(2):362–9.

    Article  CAS  PubMed  Google Scholar 

  7. Bonadonna G, Veronesi U, Brambilla C, et al. Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Natl Cancer Inst. 1990;82(19):1539–45.

    Article  CAS  PubMed  Google Scholar 

  8. Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16(8):2672–85.

    Article  CAS  PubMed  Google Scholar 

  9. Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and bowel project protocol B-27. J Clin Oncol. 2006;24(13):2019–27.

    Article  CAS  PubMed  Google Scholar 

  10. Kaufmann M, von Minckwitz G, Mamounas EP, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012;19(5):1508–16.

    Article  PubMed  Google Scholar 

  11. Liedtke C, Hatzis C, Symmans WF, Desmedt C, Haibe-Kains B, Valero V, Kuerer H, Hortobagyi GN, Piccart-Gebhart M, Sotiriou C, Pusztai L. Genomic grade index is associated with response to chemotherapy in patients with breast cancer. J Clin Oncol. 2009;27(19):3185–91.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26(8):1275–81.

    Article  PubMed  Google Scholar 

  13. von Minckwitz G, Blohmer JU, Raab G, Löhr A, Gerber B, Heinrich G, Eidtmann H, Kaufmann M, Hilfrich J, Jackisch C, Zuna I. Costa SD; German breast group, in vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study. Ann Oncol. 2005;16(1):56–63.

    Article  Google Scholar 

  14. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.

    Article  PubMed  Google Scholar 

  15. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Konecny GE, Denkert C, Nekljudova V, Mehta K, Loibl S. 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.

    Article  Google Scholar 

  16. Mazouni C, Peintinger F, Wan-Kau S, Andre F, Gonzalez-Angulo AM, Symmans WF, Meric-Bernstam F, Valero V, Hortobagyi GN, Pusztai L. Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. J Clin Oncol. 2007;25(19):2650–5.

    Article  CAS  PubMed  Google Scholar 

  17. Hennessy BT, Hortobagyi GN, Rouzier R, Kuerer H, Sneige N, Buzdar AU, Kau SW, Fornage B, Sahin A, Broglio K, Singletary SE, Valero V. Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol. 2005;23(36):9304–11.

    Article  PubMed  Google Scholar 

  18. Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25(28):4414–22.

    Article  PubMed  Google Scholar 

  19. Colleoni M, Viale G, Zahrieh D, et al. Expression of ER, PgR, Her1, Her2, and response: a study of preoperative chemotherapy. Ann Oncol. 2008;19:465–72.

    Article  CAS  PubMed  Google Scholar 

  20. Guarneri V, Broglio K, Kau SW, et al. Prognostic value of pathological complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24:1037–44.

    Article  PubMed  Google Scholar 

  21. Ellis MJ, Coop A, Singh B, et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol. 2001;19:3808–16.

    Article  CAS  PubMed  Google Scholar 

  22. Seo JH, Kim YH, Kim JS. Meta analysis of pre-operative aromatase inhibitor versus tamoxifen in postmenopausal women with hormone receptor positive breast cancer. Cancer Chemother Pharmacol. 2009;63:261–6.

    Article  CAS  PubMed  Google Scholar 

  23. Ellis MJ, Suman VJ, Hoog J, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PaM50-based intrinsic subtype-ACOSOG Z1031. J Clin Oncol. 2011;29:2342–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Llonbart-Cussac A, Guerrero A, Galan A, et al. Phase II trial with letrozole to maximum response as primary systemic therapy in postmenopausal patients with ER/PgR[+] operable breast cancer. Clin Transl Oncol. 2012;14:125–31.

    Article  Google Scholar 

  25. Semiglazov VF, Semiglazov VV, Dashyan GA, et al. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with oestrogen receptor-positive breast cancer. Cancer. 2007;110(2):244–54.

    Article  CAS  PubMed  Google Scholar 

  26. Dowsett M, Smith IE, Ebbs SR, et al. Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst. 2007;99(2):167–70.

    Article  CAS  PubMed  Google Scholar 

  27. Dowsett M, Smith I, Robertson J, et al. Endocrine therapy, new biologicals, and new study designs for presurgical studies in breast cancer. J Natl Cancer Inst Monogr. 2011;2011(43):120–3.

    Article  PubMed  Google Scholar 

  28. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Barroso-Sousa R, Silva DD, Alessi JV, Mano MS. Neoadjuvant endocrine therapy in breast cancer: current role and future perspectives. Ecancermedicalscience. 2016;10:609.

    Article  PubMed  PubMed Central  Google Scholar 

  30. von Minckwitz G, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Eiermann W, Gerber B, Hanusch C, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Kümmel S, Paepke S, Schneeweiss A, Untch M, Zahm DM, Mehta K, Loibl S. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2013;31(29):3623–30.

    Article  Google Scholar 

  31. 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, Kühn T, Nekljudova V, von Minckwitz G, German Breast Group (GBG), 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.

    Article  CAS  PubMed  Google Scholar 

  32. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD. Piccart-Gebhart M; 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Piccart-Gebhart MJ, Holmes AP, Baselga J, De Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Santillana S, Pritchard KI, Wolff AC, Jackisch C, Lang I, Untch M, Smith IE, Boyle F, Xu B, Gomez HL, Gelber RD, Perez EA. First results from the phase III ALTTO trial (BIG 2–06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC). J Clin Oncol. 2014;32(suppl; abstr LBA4):5s.

    Google Scholar 

  34. Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la 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(1):25–32.

    Article  CAS  PubMed  Google Scholar 

  35. Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross G, Valagussa P. Five-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.

    Google Scholar 

  36. Möbus V. Adjuvant dose-dense chemotherapy in breast cancer: standard of Care in High-Risk Patients. Breast Care (Basel). 2016;11(1):8–12.

    Article  Google Scholar 

  37. Lemos Duarte I, da Silveira Nogueira Lima JP, Passos Lima CS, Deeke Sasse A. Dose-dense chemotherapy versus conventional chemotherapy for early breast cancer: a systematic review with meta-analysis. Breast. 2012;21(3):343–9.

    Article  PubMed  Google Scholar 

  38. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007 Apr 15;13(8):2329–34.

    Article  CAS  PubMed  Google Scholar 

  39. Gluz O, Nitz UA, Harbeck N, Ting E, Kates R, Herr A, Lindemann W, Jackisch C, Berdel WE, Kirchner H, Metzner B, Werner F, Schütt G, Frick M, Poremba C, Diallo-Danebrock R, Mohrmann S. West German study group. Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy: results of WSG AM-01 trial. Ann Oncol. 2008;19(5):861–70.

    Article  CAS  PubMed  Google Scholar 

  40. Steger GG, Barrios C, O’Shaughnessy J, et al. Review of Capecitabine for the treatment of triple-negative early breast cancer. Cancer Res. 2010;70:96s.

    Article  Google Scholar 

  41. Lindman H, Kellokumpu-Lehtinen P-L, Huovinen R, et al. Integration of Capecitabine into Anthracycline- and Taxane-based adjuvant therapy for triple-negative early breast cancer: final subgroup analysis of the FinXX study. Cancer Res. 2010;70:96s.

    Article  Google Scholar 

  42. Kaufman PA, Awada A, Twelves C, et al. A Phase III, open-label, randomized, multicenter study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Cancer Res. 2012;72:S6–6.

    Google Scholar 

  43. Gluz O, Liedtke C, Gottschalk N, et al. Triple-negative breast cancer-current status and future directions. Ann Oncol. 2009;20:1913–27.

    Google Scholar 

  44. Kern P, Kalisch A, von Minckwitz G, Pütter C, Kolberg HC, Pott D, Kurbacher C, Rezai M, Kimmig R. Neoadjuvant, anthracycline-free chemotherapy with carboplatin and docetaxel in triple-negative, early-stage breast cancer: a multicentric analysis of rates of pathologic complete response and survival. J Chemother in print. 2015.

    Google Scholar 

  45. von Minckwitz G, Schneeweiss A, Loibl S, 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 15:747–756, 2014.

    Google Scholar 

  46. Von Minckwitz G, 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 2015; Abstract S2–04.

    Google Scholar 

  47. Sikov WM, Berry DA, Perou CM, 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;33:13–21.

    Article  CAS  PubMed  Google Scholar 

  48. Sikov WM, et al “Event-free and overall survival following neoadjuvant weekly paclitaxel and dose-dense AC +/− carboplatin and/or bevacizumab in triple-neg.

    Google Scholar 

  49. Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an international TILs working group 2014. Ann Oncol. 2015;26(2):259–71.

    Article  CAS  PubMed  Google Scholar 

  50. Denkert C, Loibl S, Müller BM, Eidtmann H, Schmitt WD, Eiermann W, Gerber B, Tesch H, Hilfrich J, Huober J, Fehm T, Barinoff J, Jackisch C, Prinzler J, Rüdiger T, Erbstösser E, Blohmer JU, Budczies J, Mehta KM, von Minckwitz G. Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol. 2013;24(11):2786–93.

    Article  CAS  PubMed  Google Scholar 

  51. Kennedy RD. The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst. 2004;96(22):1659–68.

    Article  CAS  PubMed  Google Scholar 

  52. Tutt A, Ellis P, Kilburn LS, et al. TNT: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012). San Antonio Breast Cancer Symposium. 2014;S3–01.

    Google Scholar 

  53. Von Minckwitz G, Hahnen E, Fasching PA, et al. Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (gBRCA) mutation and triple-negative breast cancer (TNBC): results from GeparSixto. J Clin Oncol. 2014;32(suppl; abstr):1005.

    Google Scholar 

  54. Lee S-J, Toi M, Lee ES, et al: A phase III trial of adjuvant capecitabine in breast cancer patients with HER2-negative pathologic residual invasive disease after neoadjuvant chemotherapy (CREATE-X, JBCRG-04). San Antonio Breast Cancer Symposium. 2015;Abstract S1–07. Presented December 9, 2015.

    Google Scholar 

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Authors and Affiliations

  1. Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Cornelia Liedtke MD PhD

  2. Marienhospital Bottrop gGmbH, Obstetrics and Gynecology/Breast Cancer Center/Gynecologic Cancer Center, Josef-Albers-Str. 70, Bottrop, 46236, Germany

    Hans-Christian Kolberg MD

Authors
  1. Cornelia Liedtke MD PhD
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  2. Hans-Christian Kolberg MD
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Correspondence to Cornelia Liedtke MD PhD .

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Editors and Affiliations

  1. The Medical School Department of Oncology, University of Sheffield, Sheffield, United Kingdom

    Lynda Wyld

  2. Athens University Medical School, Athens, Greece

    Christos Markopoulos

  3. Helsinki University Hospital, Helsinki, Finland

    Marjut Leidenius

  4. Department of Oncology & Radiotherapy, Gdańsk Medical University Department of Oncology & Radiotherapy, Gdańsk, Poland

    Elżbieta Senkus-Konefka

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Liedtke, C., Kolberg, HC. (2018). Primary Systemic Therapy for Breast Cancer. In: Wyld, L., Markopoulos, C., Leidenius, M., Senkus-Konefka, E. (eds) Breast Cancer Management for Surgeons. Springer, Cham. https://doi.org/10.1007/978-3-319-56673-3_38

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