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Influence of Neoadjuvant Therapy with Epirubicin and Docetaxel on the Expression of HER2/neu in Patients with Breast Cancer

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Abstract

Background. In primary breast cancer, the expression levels of biological markers relevant to the progression of the disease may be altered by administration of anticancer drugs. Since neoadjuvant chemotherapy with epirubicin and docetaxel is increasingly used in advanced breast cancer, our purpose was to assess the influence of this neoadjuvant chemotherapy on the expression of the growth factor receptor HER2/neu.

Patients and methods. We investigated changes of HER2/neu status by immunohistochemistry (IHC) and applied additional fluorescence in situ hybridization (FISH) in patients with potential modulation of HER2/neu status after administration of neoadjuvant chemotherapy with docetaxel and epirubicin in 97 breast cancer patients. The influence of neoadjuvant chemotherapy on HER2/neu expression was calculated by correlation of HER2/neu status before and after chemotherapy.

Results. The accuracy of HER2/neu assessment before and after neoadjuvant chemotherapy by IHC combined with FISH analysis in selected cases was 100%. The evaluation of HER2/neu status in these patients by IHC alone yielded accuracy of 93%. Neoadjuvant chemotherapy with epirubicin and docetaxel caused no significant modulation of HER2/neu status (p = 0.66).

Discussion. The administration of epirubicin and docetaxel in the neoadjuvant setting is not associated with significant changes of HER2/neu status in primary breast cancer. As a consequence, drug resistance or sensitivity is not induced by modulation of HER2/neu expression. Moreover, the time of assessment of the HER2/neu status is not a critical factor under neoadjuvant therapy with epirubicin and docetaxel.

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References

  1. King CR, Kraus MH, Aaronson SA: Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science 229: 974-976, 1985

    Google Scholar 

  2. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177-182, 1987

    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 244: 707-712, 1989

    Google Scholar 

  4. Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cussac A, Janicke F, Miller WR, Evans DB, Dugan M, Brady C, Quebe-Fehling E, Borgs M: 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 19: 3808-3816, 2001

    Google Scholar 

  5. Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glaspy JA, Slamon DJ: Phase II study of receptorenhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 16: 2659-2671, 1998

    Google Scholar 

  6. Jacobs T, Siziopikou K, Prioleau J, Raza S, Baum J, Hayes D, Schnitt S: Do prognostic marker studies on core needle biopsy specimens of breast carcinoma accurately reflect the marker status of the tumor? Mod Pathol 11: 259-264, 1998

    Google Scholar 

  7. Di Loreto C, Puglisi F, Rimondi G, Zuiani C, Anania G, Della Mea V, Beltrami CA: Large core biopsy for diagnostic and prognostic evaluation of invasive breast carcinomas. Eur J Cancer 32A: 1693-1700, 1996

    Google Scholar 

  8. Mueller-Holzner E, Fink V, Frede T, Marth C: Immunohistochemical determination of HER2 expression in breast cancer from core biopsy specimens: a reliable predictor of HER2 status of the whole tumor. Breast Cancer Res Treat 69: 13-19, 2001

    Google Scholar 

  9. Connor CS, Tawfik OW, Joyce AJ, Davis MK, Mayo MS, Jewell WR: A comparison of prognostic tumor markers obtained on image-guided breast biopsies and final surgical specimens. Am J Surg 184: 322-324, 2002

    Google Scholar 

  10. Chen AY, Liu LF: DNA topoisomerases: essential enzymes and lethal targets. Annu Rev Pharmacol Toxicol 34: 191-218, 1994

    Google Scholar 

  11. Gelmon K: The taxoids: paclitaxel and docetaxel. Lancet 344: 1267-1272, 1994

    Google Scholar 

  12. Moos PJ, Fitzpatrick FA: Taxane-mediated gene induction is independent of microtubule stabilization: induction of transcription regulators and enzymes that modulate inflammation and apoptosis. Proc Natl Acad Sci USA 95: 3896-3901, 1998

    Google Scholar 

  13. Wenzel C, Locker GJ, Pluschnig U, Zielinski CC, Rudas M, Oberhuber G, Gnant MF, Taucher S, Jakesz R, Steger GG: Phase I/II trial of weekly epidoxorubicin and docetaxel (wED) in the neoadjuvant and palliative treatment of patients with breast cancer. Cancer Chemother Pharmacol 50: 155-159, 2002

    Google Scholar 

  14. Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD: Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, Switzerland. Cancer 39: 1289-1294, 1977

    Google Scholar 

  15. Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19: 403-410, 1991

    Google Scholar 

  16. Reiner A, Neumeister B, Spona J, Reiner G, Schemper M, Jakesz R: Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer. Cancer Res 50: 7057-7061, 1990

    Google Scholar 

  17. Cohen J: A coefficient of agreement for nominal scales. Educ Psychol Meas 20: 37-46, 1960

    Google Scholar 

  18. Montgomery RB, Guzman J, O'Rourke DM, Stahl WL: Expression of Oncogenic epidermal growth factor receptor family kinases induces paclitaxel resistance and alters beta-tubulin Isotype expression. J Biol Chem 275: 17358-17363, 2000

    Google Scholar 

  19. Cleator S, Parton M, Dowsett M: The biology of neoadjuvant chemotherapy for breast cancer. Endocr Relat Cancer 9: 183-195, 2002

    Google Scholar 

  20. Rasbridge SA, Gillett CE, Seymour AM, Patel K, Richards MA, Rubens RD, Millis RR: The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma. Br J Cancer 70: 335-341, 1994

    Google Scholar 

  21. Pohl G, Rudas M, Taucher S, Stranzl T, Steger GG, Jakesz R, Pirker R, Filipits M: Expression of cell cycle regulatory proteins in breast carcinomas before and after preoperative chemotherapy. Breast Cancer Res Treat 78: 97-103, 2003

    Google Scholar 

  22. Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, Buchholz TA, Ross MI, McNeese MD, Buzdar AU, Hortobagyi GN, Singletary SE: 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, 1999

    Google Scholar 

  23. Chang J, Powles TJ, Allred DC, Ashley SE, Clark GM, Makris A, Assersohn L, Gregory RK, Osborne CK, Dowsett M: Biologic markers as predictors of clinical outcome from systemic therapy for primary operable breast cancer. J Clin Oncol 17: 3058-3063, 1999

    Google Scholar 

  24. Dowsett M, Archer C, Assersohn L, Gregory RK, Ellis PA, Salter J, Chang J, Mainwaring P, Boeddinghaus I, Johnston SR, Powles TJ, Smith IE: Clinical studies of apoptosis and proliferation in breast cancer. Endocr Relat Cancer 6: 25-28, 1999

    Google Scholar 

  25. Stearns V, Singh B, Tsangaris T, Crawford JG, Novielli A, Ellis MJ, Isaacs C, Pennanen M, Tibery C, Farhad A, Slack R, Hayes DF: A prospective randomized pilot study to evaluate predictors of response in serial core biopsies to single agent neoadjuvant doxorubicin or paclitaxel for patients with locally advanced breast cancer. Clin Cancer Res 9: 124-133, 2003

    Google Scholar 

  26. Paik S, Bryant J, Tan-Chiu E, Yothers G, Park C, Wickerham DL, Wolmark N: HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15. J Natl Cancer Inst 92: 1991-1998, 2000

    Google Scholar 

  27. Petit T, Borel C, Ghnassia J-P, Rodier J-F, Escande A, Mors R, Haegele P: Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting. Clin Cancer Res 7: 1577-1581, 2001

    Google Scholar 

  28. Zhang F, Yang Y, Smith T, Kau SW, McConathy JM, Esteva FJ, Kuerer HM, Symmans WF, Buzdar AU, Hortobagyi GN, Pusztai L: Correlation between HER-2 expression and response to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide in patients with breast carcinoma. Cancer 97: 1758-1765, 2003

    Google Scholar 

  29. Witters LM, Santala SM, Engle L, Chinchilli V, Lipton A: Decreased response to paclitaxel versus docetaxel in HER-2/neu transfected human breast cancer cells. Am J Clin Oncol 26: 50-54, 2003

    Google Scholar 

  30. Van Poznak C, Tan L, Panageas KS, Arroyo CD, Hudis C, Norton L, Seidman AD: Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer. J Clin Oncol 20: 2319-2326, 2002

    Google Scholar 

  31. Thomson TA, Hayes MM, Spinelli JJ, Hilland E, Sawrenko C, Phillips D, Dupuis B, Parker RL: HER-2/neu in Breast Cancer: Interobserver variability and performance of immunohistochemistry with 4 antibodies compared with fluorescent in situ hybridization. Mod Pathol 14: 1079-1086, 2001

    Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Vienna University Medical School, Vienna, Austria

    Susanne Taucher, Michael Gnant, Emanuel Sporn, Peter Dubsky, Sebastian Roka, Thomas Bachleitner, Florian Fitzal, Daniela Kandioler, Martina Mittlböck & Raimund Jakesz

  2. Department of Pathology, Vienna University Medical School, Vienna, Austria

    Margaretha Rudas

  3. Vienna University Medical School, Vienna, Austria

    Robert M. Mader, Catharina Wenzel & Günther G. Steger

Authors
  1. Susanne Taucher
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  2. Margaretha Rudas
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  3. Robert M. Mader
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  4. Michael Gnant
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  5. Emanuel Sporn
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  6. Peter Dubsky
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  7. Sebastian Roka
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  8. Thomas Bachleitner
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  9. Florian Fitzal
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  11. Catharina Wenzel
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  12. Günther G. Steger
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  13. Martina Mittlböck
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  14. Raimund Jakesz
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Taucher, S., Rudas, M., Mader, R.M. et al. Influence of Neoadjuvant Therapy with Epirubicin and Docetaxel on the Expression of HER2/neu in Patients with Breast Cancer. Breast Cancer Res Treat 82, 207–213 (2003). https://doi.org/10.1023/B:BREA.0000004378.15859.51

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  • DOI: https://doi.org/10.1023/B:BREA.0000004378.15859.51

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