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Exemestane as primary systemic treatment for hormone receptor positive post-menopausal breast cancer patients: a phase II trial of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-17)

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Abstract

Background A multicenter phase II study was conducted to analyze the clinical activity of the steroidal aromatase inhibitor exemestane in the neoadjuvant treatment of post-menopausal women with strongly ER- and/or PgR- positive operable breast cancer. Patients and methods From September 2000 to December 2003, 80 women were recruited for treatment with exemestane 25 mg once daily for 4 months. The primary end-point was the clinical response rate according the WHO criteria; the secondary end-points included toxicity and the number of patients who qualified for breast conserving surgery at the end of treatment, comparability of evaluation methods for response, potential alterations of hormone receptor and Her2/neu status during treatment. Results On an intention to evaluate analysis, according to the prespecified criteria the overall clinical objective response rate was 34%, the pCR rate was 3% and the rate of breast conserving surgery was 76%. When sonographic and mammographic longitudinal measurements were included in patients with missing palpation data, response rates were 38% and 41%, respectively. The tumor response was independent of the Her2/neu status which remained unchanged during treatment. In contrast, while the ER expression remained unaltered, downregulation of the PgR was observed. The treatment was well tolerated with no grade 3 and 4 toxicities except gastrointestinal (one grade 3 case) and hot flushes (two grade 3 cases). Conclusion This study shows that exemestane is effective and safe as a preoperative therapy in post-menopausal patients with strongly hormone receptor-positive breast cancer.

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References

  1. Preece PE, Wood RA, Mackie CR, Cuschieri A (1982) Tamoxifen as initial sole treatment of localised breast cancer in elderly women: a pilot study. Br Med J (Clin Res Ed) 284(6319):869–870

    Article  CAS  Google Scholar 

  2. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16(8):2672–2685

    PubMed  CAS  Google Scholar 

  3. Smith IE, Lipton L (2001) Preoperative/neoadjuvant medical therapy for early breast cancer. Lancet Oncol 2(9):561–570

    Article  PubMed  CAS  Google Scholar 

  4. Greil R (2006) The still long and winding road to neoadjuvant systemic therapy as the standard of care in breast cancer. Breast Care 1(6):2–7

    Article  Google Scholar 

  5. Macaskill EJ, Renshaw L, Dixon JM (2006) Neoadjuvant use of hormonal therapy in elderly patients with early or locally advanced hormone receptor-positive breast cancer. Oncologist 11(10):1081–1088

    Article  PubMed  CAS  Google Scholar 

  6. Boccardo F, Rubagotti A, Bruzzi P, Cappellini M, Isola G, Nenci I, Piffanelli A, Scanni A, Sismondi P, Santi L et al (1990) Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group. J Clin Oncol 8(8):1310–1320

    PubMed  CAS  Google Scholar 

  7. Roche H, Kerbrat P, Bonneterre J, Fargeot P, Fumoleau P, Monnier A, Clavere P, Goudier MJ, Chollet P, Guastalla JP et al (2006) Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial. Ann Oncol 17(8):1221–1227

    Article  PubMed  CAS  Google Scholar 

  8. Jakesz R, Hausmaninger H, Kubista E, Gnant M, Menzel C, Bauernhofer T, Seifert M, Haider K, Mlineritsch B, Steindorfer P et al (2002) Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer–Austrian Breast and Colorectal Cancer Study Group Trial 5. J Clin Oncol 20(24):4621–4627

    Article  PubMed  CAS  Google Scholar 

  9. Berry DA, Cirrincione C, Henderson IC, Citron ML, Budman DR, Goldstein LJ, Martino S, Perez EA, Muss HB, Norton L et al (2006) Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295(14):1658–1667

    Article  PubMed  CAS  Google Scholar 

  10. Dixon JM, Renshaw L, Bellamy C, Stuart M, Hoctin-Boes G, Miller WR (2000) The effects of neoadjuvant anastrozole (Arimidex) on tumor volume in postmenopausal women with breast cancer: a randomized, double-blind, single-center study. Clin Cancer Res 6(6):2229–2235

    PubMed  CAS  Google Scholar 

  11. Mustacchi G, Ceccherini R, Milani S, Pluchinotta A, De Matteis A, Maiorino L, Farris A, Scanni A, Sasso F (2003) Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial. Ann Oncol 14(3):414–420

    Article  PubMed  CAS  Google Scholar 

  12. Bates T, Riley DL, Houghton J, Fallowfield L, Baum M, Belli P, Costantini M, Malaspina C, Magistrelli A, Latorre G et al (1991) Breast cancer in elderly women: a Cancer Research Campaign trial comparing treatment with tamoxifen and optimal surgery with tamoxifen alone. The Elderly Breast Cancer Working Party MRI accuracy in residual disease evaluation in breast cancer patients treated with neoadjuvant chemotherapy. Br J Surg 78(5):591–594

    Article  PubMed  CAS  Google Scholar 

  13. Gazet JC, Ford HT, Coombes RC, Bland JM, Sutcliffe R, Quilliam J, Lowndes S (1994) Prospective randomized trial of tamoxifen vs surgery in elderly patients with breast cancer. Eur J Surg Oncol 20(3):207–214

    PubMed  CAS  Google Scholar 

  14. Robertson JF, Ellis IO, Elston CW, Blamey RW (1992) Mastectomy or tamoxifen as initial therapy for operable breast cancer in elderly patients: 5-year follow-up. Eur J Cancer 28A(4–5):908–910

    Article  PubMed  CAS  Google Scholar 

  15. Buzdar AU (2003) Advances in endocrine treatments for postmenopausal women with metastatic and early breast cancer. Oncologist 8(4):335–341

    Article  PubMed  CAS  Google Scholar 

  16. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365(9453):60–62

    Article  PubMed  CAS  Google Scholar 

  17. Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H et al (2005) Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 366(9484):455–462

    Article  PubMed  CAS  Google Scholar 

  18. Harper-Wynne CL, Sacks NP, Shenton K, MacNeill FA, Sauven P, Laidlaw IJ, Rayter Z, Miall S, Howes A, Salter J et al (2002) Comparison of the systemic and intratumoral effects of tamoxifen and the aromatase inhibitor vorozole in postmenopausal patients with primary breast cancer. J Clin Oncol 20(4):1026–1035

    Article  PubMed  CAS  Google Scholar 

  19. Milla-Santos A, MLCNPJRLCJPM (2003) Anastrozole is an effective neo-adjuvant therapy for patients with hormone-dependent, locally-advanced breast cancer irrespective of cerbb2. Proc Am Soc Clin Oncol 22:39

    Google Scholar 

  20. Smith IE, Dowsett M, Ebbs SR, Dixon JM, Skene A, Blohmer JU, Ashley SE, Francis S, Boeddinghaus I, Walsh G (2005) Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol 23(22):5108–5116

    Article  PubMed  CAS  Google Scholar 

  21. Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J, Mauriac L, Ellis M, Lassus M, Chaudri-Ross HA et al (2001) Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol 12(11):1527–1532

    Article  PubMed  CAS  Google Scholar 

  22. Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cussac A, Janicke F, Miller WR, Evans DB, Dugan M, Brady C et al (2001) 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(18):3808–3816

    PubMed  CAS  Google Scholar 

  23. Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, Blohmer JU, Eiermann W, Jackesz R, Jonat W 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(12):1940–1949

    Article  PubMed  Google Scholar 

  24. Miller WR, Dixon JM (2002) Endocrine and clinical endpoints of exemestane as neoadjuvant therapy. Cancer Control 9(2 Suppl):9–15

    PubMed  Google Scholar 

  25. Geisler J, King N, Anker G, Ornati G, Di Salle E, Lonning PE, Dowsett M (1998) In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res 4(9):2089–2093

    PubMed  CAS  Google Scholar 

  26. Krainick U, Astner A, Jonat W, Wallwiener D (2003) Phase II study to define safety and efficacy of exemestane as preoperative therapy for postmenopausal patients with primary breast cancer - final results of the german neoadjuvant aromasin initiative (genari). Breast Cancer Res Treat 82:239

    Google Scholar 

  27. Tubiana-Hulin MSF (2004) Response to neo-adjuvant exemestane in postmenopausal breast cancer patients: correlation with biological factors measured by real-time quantitative rt-pcr (qrt-pcr). Proc Am Soc Clin Oncol 22:538

    Google Scholar 

  28. Semiglazov V, Kletsel A, Zhiltzova V, Ivanov V, Dashyan G, Bozhok A, Melnikova O, Paltuev R, Berstein L (2005) Exemestane (e) vs tamoxifen (t) as neoadjuvant endocrine therapy for postmenopausal women with er+ breast cancer (t2n1-2, t3n0-1, t4n0m0). Proc Am Soc Clin Oncol 23:530

    Google Scholar 

  29. Remmele W, Schicketanz KH (1993) Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS). Pathol Res Pract 189(8):862–866

    PubMed  CAS  Google Scholar 

  30. WHO (1979) WHO handbook for reporting results of cancer treatment. WHO Handbook

  31. McGuire WL, Osborne CK, Clark GM, Knight WA 3rd (1982) Steroid hormone receptors and carcinoma of the breast. Am J Physiol 243(2):E99–E102

    PubMed  CAS  Google Scholar 

  32. Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ (1999) Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration-approved scoring system. J Clin Oncol 17(7):1983–1987

    PubMed  CAS  Google Scholar 

  33. Fisher B, Gunduz N, Coyle J, Rudock C, Saffer E (1989) Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res 49(8):1996–2001

    PubMed  CAS  Google Scholar 

  34. Fisher B, Gunduz N, Saffer EA (1983) Interrelation between tumor cell proliferation and 17-fluoresceinated estrone binding following primary tumor removal, radiation, cyclophosphamide, or tamoxifen. Cancer Res 43(11):5244–5247

    PubMed  CAS  Google Scholar 

  35. Namer M, Fargeot P, Roche H, Campone M, Kerbrat P, Romestaing P, Monnier A, Luporsi E, Montcuquet P, Bonneterre J (2006) Improved disease-free survival with epirubicin-based chemoendocrine adjuvant therapy compared with tamoxifen alone in one to three node-positive, estrogen-receptor-positive, postmenopausal breast cancer patients: results of French Adjuvant Study Group 02 and 07 trials. Ann Oncol 17(1):65–73

    Article  PubMed  CAS  Google Scholar 

  36. Gil Gil M, Barnadas A, Cirera L, Tusqets I, Munoz N, Arcusa A, Prieto L, Moreno A, Graupera J, Margeli M (2004) Primary hormonal therapy with exemestane in patients with breast tumors >3 m in diameter: results of a Spanish multicenter phase II trial. J Clin Oncol, 2004, ASCO Ann Meet Proc 22(14S):603

    Google Scholar 

  37. Fukutomi T (2006) Clinical practice and outcome of breast-conserving treatment: the effectiveness of preoperative systemic chemotherapy. Breast Cancer 13(2):147–151

    Article  PubMed  Google Scholar 

  38. Belli P, Costantini M, Malaspina C, Magistrelli A, Latorre G, Bonomo L (2006) MRI accuracy in residual disease evaluation in breast cancer patients treated with neoadjuvant chemotherapy. Clin Radiol 61(11):946–953

    Article  PubMed  CAS  Google Scholar 

  39. Cui X, Schiff R, Arpino G, Osborne CK, Lee AV (2005) Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol 23(30):7721–7735

    Article  PubMed  CAS  Google Scholar 

  40. Colleoni M, Viale G, Zahrieh D, Pruneri G, Gentilini O, Veronesi P, Gelber RD, Curigliano G, Torrisi R, Luini A et al (2004) Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment. Clin Cancer Res 10(19):6622–6628

    Article  PubMed  CAS  Google Scholar 

  41. Rouzier R, Pusztai L, Delaloge S, Gonzalez-Angulo AM, Andre F, Hess KR, Buzdar AU, Garbay JR, Spielmann M, Mathieu MC et al (2005) Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer. J Clin Oncol 23(33):8331–8339

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Karin Wetzlinger for her secretarial assistance, Rajam Csordas-Iyer for helpful comments and Michaela Schachner for her assistance in preparation this article. We also would like to acknowledge Pfizer Austria for their contribution to this study.

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Authors and Affiliations

  1. IIIrd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Disease, Laboratory of Immunological and Molecular Cancer Research, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, 5020, Salzburg, Austria

    Brigitte Mlineritsch & Richard Greil

  2. Department of Surgery, BHS Hospital, Linz, Austria

    Christoph Tausch

  3. Division of Special Gynaecology, General Hospital, Medical University of Vienna, Vienna, Austria

    Christian Singer

  4. Department of Gynaecology, Medical University of Graz, Graz, Austria

    Gero Luschin-Ebengreuth

  5. Department of Surgery, Medical University of Vienna, Vienna, Austria

    Raimund Jakesz, Peter Wohlmuth & Michael Gnant

  6. Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria

    Ferdinand Ploner

  7. Department of Surgery, Hanusch Medical Center, Vienna, Austria

    Michael Stierer

  8. Department of Surgery, Wolfsberg Hospital, Wolfsberg, Austria

    Elisabeth Melbinger

  9. Department of Special Gynaecology, Paracelsus Medical University Salzburg, Salzburg, Austria

    Christian Menzel

  10. Department of Surgery, Klagenfurt Hospital, Klagenfurt, Austria

    Andrea Urbania

  11. Department of Internal Medicine 3, Center for Hematology and Medical Oncology, General Hospital Linz, Linz, Austria

    Michael Fridrik

  12. Department of Oncology, General Hospital, Medical University of Vienna, Vienna, Austria

    Günther Steger

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  1. Brigitte Mlineritsch
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on behalf of the Austrian Breast, Colorectal Cancer Study Group (ABCSG)

Corresponding author

Correspondence to Richard Greil.

Appendix

Appendix

Apart from the authors of this article, members of the Austrian Breast and Colorectal Cancer Study Group participating in Trial 17 included the following:

H. Hausmaninger, M. Moik, C. Rass, R. Reitsamer, G. Russ (Paracelsus Medical University Salzburg, IIIrd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Disease and Laboratory of Immunological and Molecular Cancer Research and Department of Special Gynaecology, Paracelsus Medical University Salzburg);

T. Bachleitner-Hoffmann, R. Bartsch, P. Blaha, P. Dubsky, F. Fitzal, T. D. Kandioler, P. Panhofer, U. Pluschnig, S. Schoppmann, S. Taucher, C. Wenzel (Departments of Surgery and Internal Medicine I, Division of Oncology, Medical University of Vienna, Vienna);

H. Samonigg, H. Stöger, M. Schmid (Departments of Internal Medicine and Surgery, Medical University of Graz, and Second Department of Surgery, Graz Hospital, Graz);

A. Galid, M. Seifert (Department of Gynecology, Medical University of Vienna, Vienna);

F. Kugler, G. Michlmayer, S. Pöstlberger (Departments of Surgery and Internal Medicine, BHS Hospital, Linz);

H. Matzinger, H. Spoula (Department of Surgery, Breast-Center-Hanusch Medical Center, Vienna);

I. Thiel, G. Zehtleitner (Department of Gynecology, Medical University of Graz, Graz);

R. Greul, G. Hochreiner, G. Wahl (First Medical Department, Linz Hospital, Linz).

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Mlineritsch, B., Tausch, C., Singer, C. et al. Exemestane as primary systemic treatment for hormone receptor positive post-menopausal breast cancer patients: a phase II trial of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-17). Breast Cancer Res Treat 112, 203–213 (2008). https://doi.org/10.1007/s10549-007-9843-x

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