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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

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Abstract

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 for 4 cycles) followed either by D (docetaxel 100 mg/m2 × 4 cycles; EC–D) or DCb (docetaxel 75 mg/m2 plus carboplatin AUC 6 × 4 cycles; EC–DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC–D, 48 EC–DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC–D and 14 patients (30 %) with EC–DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56–83) in the EC–D arm and 77 % (95 % CI 65–87) in the EC–DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC–D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

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References

  1. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  PubMed  CAS  Google Scholar 

  2. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Børresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874

    Article  PubMed  Google Scholar 

  3. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lønning PE, Brown PO, Børresen-Dale AL, Botstein D (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423

    Article  PubMed  CAS  Google Scholar 

  4. Perreard L, Fan C, Quackenbush JF, Mullins M, Gauthier NP, Nelson E, Mone M, Hansen H, Buys SS, Rasmussen K, Orrico AR, Dreher D, Walters R, Parker J, Hu Z, He X, Palazzo JP, Olopade OI, Szabo A, Perou CM, Bernard PS (2006) Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay. Breast Cancer Res 8:R23

    Article  PubMed  Google Scholar 

  5. Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, Perou CM (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7:96

    Article  PubMed  Google Scholar 

  6. Prat A, Perou CM (2011) Deconstructing the molecular portraits of breast cancer. Mol Oncol 5(1):5–23

    Article  PubMed  CAS  Google Scholar 

  7. Perou CM (2010) Molecular stratification of triple-negative breast cancer. Oncologist 15(5s):39–48

    Article  PubMed  CAS  Google Scholar 

  8. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10:5367–5374

    Article  PubMed  CAS  Google Scholar 

  9. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13:4429–4434

    Article  PubMed  Google Scholar 

  10. 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 (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26:1275–1281

    Article  PubMed  Google Scholar 

  11. Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11:5678–5685

    Article  PubMed  CAS  Google Scholar 

  12. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13:2329–2334

    Article  PubMed  CAS  Google Scholar 

  13. Carey LA, Rugo HS, Marcom PK, Irvin W, Ferraro M, Burrows E, He X, Perou CM, Winer EP, on behalf of the Translational Breast Cancer Research Consortium (2008) TBCRC 001: EGFR inhibition with cetuximab added to carboplatin in metastatic triple-negative (basal-like) breast cancer. J Clin Oncol 26 (15s):abstr 1009

    Google Scholar 

  14. O’Shaughnessy J, Weckstein DJ, Vukelja SJ, McIntyre K, Krekow L, Holmes FA, Asmar L, Blum JL (2007) Preliminary results of a randomized phase II study of weekly irinotecan/carboplatin with or without cetuximab in patients with metastatic breast cancer. Breast Cancer Res Treat 106(1s):S32: abstr 308

    Google Scholar 

  15. Baselga J, Stemmer S, Pego A, Chan A, Goeminne J-C, Graas M-P, Kennedy J, Ciruelos Gil EM, Zubel A, Groos J, Kia U, Schneeweiss A (2010) Cetuximab + cisplatin in estrogen receptor-negative, progesterone receptor-negative, HER2-negative (triple-negative) metastatic breast cancer: results of the randomized phase ii BALI-1 tr. Cancer Res 70(24s):95s

    Google Scholar 

  16. O’Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C (2011) Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 364:205–214

    Article  PubMed  Google Scholar 

  17. Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M, Dent R, Lubinski J, Narod S (2010) Pathologic complete response rates in young women with BRCA 1 positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 28:375–379

    Article  PubMed  CAS  Google Scholar 

  18. Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, Fatima A, Gelman RS, Ryan PD, Tung NM, De Nicolo A, Ganesan S, Miron A, Colin C, Sgroi DC, Ellisen LW, Winer EP, Garber JE (2010) Efficacy of neoadjuvant cisplatin in triple negative breast cancer. J Clin Oncol 28:1145–1153

    Article  PubMed  CAS  Google Scholar 

  19. Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD (2003) A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 12(5):320–327

    Article  PubMed  Google Scholar 

  20. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  21. National Cancer Institute (2006) Common terminology criteria for adverse events (NCI-CTCAE) version 3.0. http://ctep.cancer.gov/. Accessed 3 Apr 2012

  22. Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, Quackenbush JF, Stijleman IJ, Palazzo J, Marron JS, Nobel AB, Mardis E, Nielsen TO, Ellis MJ, Perou CM, Bernard PS (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27:1160–1167

    Article  PubMed  Google Scholar 

  23. Arup Laboratories (2012) PAM50 Breast Cancer Intrinsic Classifier Information. http://www.aruplab.com/Lab-Tests/General-Oncology/PAM50/index.jsp. Accessed 3 April 2012

  24. Loibl S, von Minckwitz G, Blohmer JU, Costa S, Eidtmann H, Fasching PA, Gerber B, Hanusch C, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Konecny G, Denkert C, Nekljudova V, Mehta K, Untch M (2011) pCR as surrogate in HER2-positive patients treated with trastuzumab. Cancer Res 71(24); supp:111s. S5–S4

  25. O’Shaughnessy J, Schwartzberg LS, Danso MA, Rugo HS, Miller K, Yardley DA, Carlson RW, Finn RS, Charpentier E, Freese M, Gupta S, Blackwood-Chirchir A, Winer EP (2011) A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). J Clin Oncol 29(81s):abstr 1007

    Google Scholar 

  26. Scully R (2011) Interactions between BRCA proteins and DNA structure. Exp Cell Res 264(1):67–73

    Article  Google Scholar 

  27. Tassone P, Tagliaferri P, Perricelli A, Blotta S, Quaresima B, Martelli ML, Goel A, Barbieri V, Costanzo F, Boland CR, Venuta S (2003) BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. Br J Cancer 88(8):1285–1291

    Article  PubMed  CAS  Google Scholar 

  28. Roy V, Pockaj BA, Northfelt DW, Allred JB, Liu H, Nikcevich DA, Mattar BI, Perez EA (2008) N0338 phase ll trial of docetaxel and carboplatin administered every two weeks as induction therapy for stage ll or lll breast cancer. J Clin Oncol 26(15S, pt1):21s Abstract 563

    Google Scholar 

  29. Chang HR, Glaspy J, Allison MA, Kass FC, Elashoff R, Chung DU, Gornbein J (2010) Differential response of triple-negative breast cancer to a docetaxel and carboplatin-based neoadjuvant treatment. Cancer 116(18):4227–4237

    Article  PubMed  CAS  Google Scholar 

  30. Kern P, Kimmig R, Kolberg HC, Pott D, Kalisch A, Otterbach F (2010) Neoadjuvant carboplatin and docetaxel for triple-negative breast cancer. Am Soc Clin Oncol Breast Cancer Symp. Abstract 279

  31. Arun B, Bayraktar S, Liu DD, Gutierrez Barrera AM, Atchley D, Pusztai L, Litton JK, Valero V, Meric-Bernstam F, Hortobagyi GN, Albarracin C (2011) Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and non carriers: a single institution experience. J Clin Oncol 29:3739–3746

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Authors thank Dr. A. Plazaola from the Onkologikoa, Dr. S. Gonzalez from the H. Mutua de Terrassa, Dr. B. Munarriz from the Hospital la Fe, Dr. J. R. de la Haba from the H. U. Reina Sofia, Dr. A. Miguel from the Hospital Althaia Xarxa Assistencial Universitaria de Manresa, Dr. A. Arcusa from the Hospital Sanitari de Terrassa, Dr. M. Muñoz from the Hospital Clinic i Provincial, Dr. M. Gil from the Instituto Catalan de Oncologia de Hospitalet, Dr. R. Andres from the Hospital Universitario Lozano Blesa, Dr. A. Velasco from the Hospital universitario de la Princesa, Dr. J. M. Baena from the Hospital Puerta del Mar, Dr. P. Sanchez-Rovira from the Complejo Hospitalario de Jaen, and the respective pathology departments of the involved sites for their valuable support in the inclusion of patients in this study. This trial was partially supported by Pfizer S.L.U.

Disclosure

All authors have declared no conflicts of interest.

Author information

Authors and Affiliations

  1. Medical Oncology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain

    E. Alba, N. Ribelles & A. Sanchez-Muñoz

  2. Medical Oncology Department, Hospital Virgen de la Salud, Toledo, Spain

    J. I. Chacon & R. Alvarez

  3. Medical Oncology Department, Hospital Clinico Universitario, Fundación INCLIVA, Valencia, Spain

    A. Lluch

  4. Medical Oncology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain

    A. Anton

  5. Medical Oncology Department, Centro Integral Oncologico Clara Campal, Madrid, Spain

    L. Estevez

  6. Medical Oncology Department, Hospital Universitario Germans Trias I Pujol, Barcelona, Spain

    B. Cirauqui

  7. Spanish Breast Cancer Research Group, GEICAM, Madrid, Spain

    E. Carrasco, C. Rodriguez-Martin & M. J. Escudero

  8. Medical Oncology Department, Complejo Hospitalario Universitario a Coruña, A Coruna, Spain

    L. Calvo

  9. Medical Oncology Department, Corporacion Sanitaria Parc Tauli, Barcelona, Spain

    M. A. Segui

  10. Pathology Department, Hospital Virgen de la Salud, Toledo, Spain

    R. Sanchez

  11. Pathology Department, Hospital Universitario Clinico San Carlos, Madrid, Spain

    J. A. Lopez Garcia-Asenjo

  12. Medical Oncology Department, Hospital del Mar, Barcelona, Spain

    J. Albanell

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  1. E. Alba
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  3. A. Lluch
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  7. E. Carrasco
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  10. N. Ribelles
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  11. R. Alvarez
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  12. A. Sanchez-Muñoz
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  13. R. Sanchez
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  14. J. A. Lopez Garcia-Asenjo
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  15. C. Rodriguez-Martin
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  16. M. J. Escudero
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  17. J. Albanell
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Corresponding author

Correspondence to E. Alba.

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This study was conducted on behalf of GEICAM.

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Alba, E., Chacon, J.I., Lluch, A. 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 136, 487–493 (2012). https://doi.org/10.1007/s10549-012-2100-y

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  • DOI: https://doi.org/10.1007/s10549-012-2100-y

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