Skip to main content

Tumour molecular subtyping according to hormone receptors and HER2 status defines different pathological complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

Clinical and Translational Oncology volume 10, Article number: 646 (2008) Cite this article

Abstract

Purpose

To study the role of breast cancer molecular subtypes according to hormone receptors and HER2 status as a predictive factor for pathological complete response (pCR) to neoadjuvant chemotherapy.

Patients and methods

Eligible patients received one of the two chemotherapy schedules every two weeks with prophylactic growth factor support; schedule A: epirubicin 90 mg/m2-cyclophosphamide 600 mg/m2 d1 for 3 cycles followed by a second sequence with paclitaxel (P) 150 mg/m2-gemcitabine (G) 2500 mg/m2 d1±trastuzumab (T) 2 mg/kg/week according to HER2 status (n=73); schedule B: adriamycin (40 mg/m2) d1 plus P (150 mg/m2)-G (2000 mg/m2) d2 for 6 cycles (n=54). Subsequently, patients underwent surgery, radiotherapy and/or adjuvant hormonal therapy according to standard practice.

Results

A total of 127 patients were evaluated. Forty-three patients (33.9%) achieved a pCR (50% in patients with HER2+tumours treated with T). Patients treated with chemotherapy alone (n=107, 18 HER2+) had a pCR of 32% (p=0.068). The pCR rate for patients with triple negative (HR and HER2−) cancers was 58.3%, 39.5% for HER2+ and 5.4% for ER/PR+ and HER2− (p<0.001). No differences in disease-free survival (DFS) were noted as a function of pCR, HER2 and HR status or treatment received (±T). However, statistical differences in DFS were observed as a function of whether patients had + or − axillar lymph nodes. Patients with + lymph node disease did worse (3 years DFS of 53.7% vs. 81.5%, p=0.025). Breastconserving surgery was performed in 77 patients (60.6%).

Conclusion

Tumour molecular subtyping defines different pCR to neoadjuvant chemotherapy (NC) but has no impact over DFS in patients with LABC. Although no significant correlation between HER2 status and trastuzumab therapy with pCR was found, probably due to the small number of patients, a favourable trend was observed in the group of HER2+ tumours treated with T.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Jensen OM, Esteve J, Moller H et al (1990) Cancer in the European community and its member states. Eur J Cancer 26:1167–1256

    PubMed  CAS  Google Scholar 

  2. American Cancer Society (1995) Cancer facts and figures. National Media Office, New York, NY [Brochure]

    Google Scholar 

  3. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717

    Article  CAS  Google Scholar 

  4. Harris JR, Marrow M, Bonadonna G (1993) Cancer of the breast. In Devita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 4th Edn. Lippincott, Philadelphia, PA, pp 1264–1332

    Google Scholar 

  5. Mouridsen HT (1992) Systemic therapy of advanced breast cancer. Drugs 44:17–28

    PubMed  Google Scholar 

  6. Carmichael J, Possinger K, Philip P et al (1995) Advanced breast cancer: a phase II trial with gemcitabine. J Clin Oncol 17:2731–2736

    Google Scholar 

  7. Possinger K, Kaufmann M, Coleman R et al (1999) Phase II study of gemcitabine as first-line chemotherapy in patients with advanced or metastatic breast cancer. Anti-cancer Drugs 10: 155–162

    PubMed  Article  CAS  Google Scholar 

  8. Spielman M, Kalla S, Llombart-Cussac A et al (1997) Activity of gemcitabine in metastatic breast cancer (MBC) patients previously treated with anthracycline containing regimens. Eur J Cancer 33:A663

    Google Scholar 

  9. Blackstein M, Vogel CL, Ambinder R et al (1997) Phase II study of gemcitabine in patients with metastatic breast cancer. Eur J Cancer 33:A664

    Google Scholar 

  10. Brodowicz T, Moslinger R, Herscovici V et al (1998) Second and third line treatment of metastatic breast cancer with gemcitabine. Eur J Cancer 34:S44

    Article  Google Scholar 

  11. Akrivakis K, Schmid P, Flath B et al (1999) Prolonged infusion of gemcitabine in stage IV breast cancer: a phase I study. Anti-cancer Drugs 10: 525–531

    PubMed  Article  CAS  Google Scholar 

  12. Schmid P, Akrivakis K, Flath B et al (1999) Phase II trial of gemcitabine as prolonged infusion in metastatic breast cancer. Anti-cancer Drugs 10:625–631

    PubMed  Article  CAS  Google Scholar 

  13. Bonadonna G, Valagussa P, Brambilla C (1998) Primary chemotherapy in operable breast cancer: eight year experience at the Milan Cancer Institute. J Clin Oncol 16:93–100

    PubMed  CAS  Google Scholar 

  14. Kuerer HM, Newman LA, Smith TL (1999) Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460–469

    PubMed  CAS  Google Scholar 

  15. Van der Hage JA, van de Velde CJ, Julien JP et al (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer Trial 10902. J Clin Oncol 19:4224–4237

    PubMed  Google Scholar 

  16. Fisher B, Bryant J, Wolmark N et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685

    PubMed  CAS  Google Scholar 

  17. Gilmore PM, McCabe N, Quinn JE et al (2004) BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase 3. Cancer Res 64:4148–4154

    PubMed  Article  CAS  Google Scholar 

  18. Conti F, Sergi D, Foggi P et al (2007) New combination chemotherapy regimens in the primary treatment of operable breast cancer. Clin Ther 158:55–75

    CAS  Google Scholar 

  19. Hess KR, Anderson K, Symmans WF et al (2006) Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol 24:4236–4244

    PubMed  Article  CAS  Google Scholar 

  20. Rouzier R, Rajan R, Wagner P et al (2005) Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci USA 102:8315–8320

    PubMed  Article  CAS  Google Scholar 

  21. Baselga J, Tripathy D, Mendelson J et al (1996) Phase II study of weekly intravenous recombinant humanized antip185HER2 monoclonal antibody in patients with Her2/neu overexpressing metastatic breast cancer. J Clin Oncol 14:737–744

    PubMed  CAS  Google Scholar 

  22. Cobleigh MA, Vogel CL, Tripathy D et al (1998) Efficacy and safety of Herceptin as a single agent in 222 women with HER2 overexpression who relapsed following chemotherapy for metastatic breast cancer. Proc Am Soc Clin Oncol 17:abstr 376

    Google Scholar 

  23. Smith I, Procter M, Gelber RD et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369:29–36

    PubMed  Article  CAS  Google Scholar 

  24. Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable Her2-positive breast cancer. N Engl J Med 353:1673–1684

    PubMed  Article  CAS  Google Scholar 

  25. Slamon D, Eiermann W, Robert N et al (2005) Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC.T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC.TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients: BCIRG 006 study. Breast Cancer Res Treat 94:S5

    Google Scholar 

  26. Slamon D, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792

    PubMed  Article  CAS  Google Scholar 

  27. Ross JS, Fletcher JA (1998) The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Stem Cells 16:413–428

    PubMed  CAS  Article  Google Scholar 

  28. Perou CM, Sorlie T, Eisen MD et al (2000) Molecular portraits of human breast tumors. Nature 406:747–752

    PubMed  Article  CAS  Google Scholar 

  29. Rouzier R, Perou CM, Symmans WF et al (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11:5678–5685

    PubMed  Article  CAS  Google Scholar 

  30. Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 198:10869–10874

    Article  Google Scholar 

  31. Sorlie T, Tibshirani R, Parker J et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423

    PubMed  Article  CAS  Google Scholar 

  32. Sotiriou C, Neo SY, McShane LM et al (2003) Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA 100:10393–10398

    PubMed  Article  CAS  Google Scholar 

  33. Kaufmann M, Hortobagyi GN, Goldhirsch A et al (2006) Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 24:1940–1949

    PubMed  Article  Google Scholar 

  34. Mamounas EP (2005) Can we approach zero relapse in breast cancer? Oncologist 10:9–17

    PubMed  Article  CAS  Google Scholar 

  35. Bear HD, Anderson S, Brown A et al (2003) The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21:4165–4174

    PubMed  Article  CAS  Google Scholar 

  36. Smith I, Heys SD, Hutcheon AW et al (2002) Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 20:1456–1466

    PubMed  Article  CAS  Google Scholar 

  37. Gianni L, Baselga J, Eiermann W et al (2005) European Cooperative Trial in operable breast cancer (ECTO): improved freedom from progression from adding paclitaxel to doxorubicin followed by cyclophosphamide methotrexate and fluorouracil. Proc Am Soc Clin Oncol 7s:Abstr 513

    Google Scholar 

  38. Sánchez-Rovira P, Medina MB, Mohedano N et al (1998) Results from a phase II study of gemcitabine in combination with paclitaxel in metastatic breast cancer. Ann Oncol 9:16 [abstract 77]

    Article  Google Scholar 

  39. Murad AM, Guimaraes RC, Aragao BC et al (2001) Phase III trial of the use of paclitaxel and gemcitabine as a salvage treatment in metastatic breast cancer. Am J Clin Oncol 24:264–268

    PubMed  Article  CAS  Google Scholar 

  40. Colomer R, Llombart A, Llunch A et al (2004) Biweekly paclitaxel and gemcitabine in advanced breast cancer. Phase II trial and predictive value of HER2 extracellular domain (ECD). Ann Oncol 15:201–206

    PubMed  Article  CAS  Google Scholar 

  41. Citron M, Berry D, Cirrincione C et al (2003) Randomized trial of dose-dense versus conventionally scheduled and sequential versus combination chemotherapy as postoperative adjuvant treatment for node-positive primary breast cancer: First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21: 1431–1439

    PubMed  Article  CAS  Google Scholar 

  42. Estévez LG, Gradishar WJ (2004) Evidence-based use of neoadjuvant taxane in operable and inoperable breast cancer. Clin Cancer Res 10:3249–3261

    PubMed  Article  Google Scholar 

  43. Kandioler-Eckersberger D, Ludwig C, Rudas M et al (2000) TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients. Clin Cancer Res 6:50–56

    PubMed  CAS  Google Scholar 

  44. Buzdar AU, Valero V, Ibrahim NK et al (2007) 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 13:228–233

    PubMed  Article  CAS  Google Scholar 

  45. Coudert BP, Arnould L, Moreau L et al (2006) Pre-operative systemic (neo-adjuvant) therapy with trastuzumab and docetaxel for HER2-overexpressing stage II or III breast cancer: results of a multicenter phase II trial. Ann Oncol 17:409–414

    PubMed  Article  CAS  Google Scholar 

  46. Colleoni M, Viale G, Zahrieh D et al (2004) Chemo therapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment. Clin Cancer Res 10:6622–6628

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Oncology, Complejo Hospitalario de Jaén, Jaén, Spain

    Alfonso Sánchez-Muñoz, Ana María García-Tapiador, Esther Martínez-Ortega, Rosario Dueñas-García, Ana Jaén-Morago, Ana Laura Ortega-Granados, Mónica Fernández-Navarro, Capilla de la Torre-Cabrera & Pedro Sánchez-Rovira

  2. Medical Oncology, Complejo Hospitalario de Jaén, Avda. Ejército Español, s/n, ES-23007, Jaén, Spain

    Alfonso Sánchez-Muñoz

  3. Department of General Surgery, Complejo Hospitalario de Jaén, Jaén, Spain

    Basilio Dueñas & Ana Isabel Rueda

  4. Department Radiology, Complejo Hospitalario de Jaén, Jaén, Spain

    Francisco Morales

  5. Department Pathology, Complejo Hospitalario de Jaén, Jaén, Spain

    César Ramírez-Torosa & María Dolores Martín-Salvago

Authors
  1. Alfonso Sánchez-Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana María García-Tapiador
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Esther Martínez-Ortega
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosario Dueñas-García
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana Jaén-Morago
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana Laura Ortega-Granados
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mónica Fernández-Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Capilla de la Torre-Cabrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Basilio Dueñas
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ana Isabel Rueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Francisco Morales
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. César Ramírez-Torosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. María Dolores Martín-Salvago
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Pedro Sánchez-Rovira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alfonso Sánchez-Muñoz.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sánchez-Muñoz, A., García-Tapiador, A.M., Martínez-Ortega, E. et al. Tumour molecular subtyping according to hormone receptors and HER2 status defines different pathological complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Clin Transl Oncol 10, 646 (2008). https://doi.org/10.1007/s12094-008-0265-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12094-008-0265-y

Keywords

  • Neoadjuvant chemotherapy
  • Pathological complete response
  • HER2
  • Estrogen and progesterone receptors
  • Triple negative
  • Trastuzumab