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Pathology & Oncology Research

, Volume 21, Issue 4, pp 977–984 | Cite as

One-Year Neoadjuvant Endocrine Therapy in Breast Cancer

  • Orsolya Rusz
  • András Vörös
  • Zoltán Varga
  • Gyöngyi Kelemen
  • Gabriella Uhercsák
  • Alíz Nikolényi
  • Katalin Ormándi
  • Zsolt Simonka
  • Zsuzsanna KahánEmail author
Research

Abstract

The evaluation of the effects of 1-year endocrine therapy (NET) was aimed at. A retrospective analysis of 42 cases with 46 stage II–III invasive, hormone receptor-positive, HER2-negative breast cancers was performed. One-year NET was planned with letrozole (n = 33, postmenopausal group), or with goserelin plus letrozole (n = 7) or with goserelin plus tamoxifen (n = 2) (premenopausal group). Surgery was performed in accordance with the initial stage and the response to therapy. With regard to the tumor remaining in the surgical specimen, risk groups were constructed: Group 1: stage 0, pathological complete regression (pCR); Group 2: stages IA-IIA; Group 3: stages ≥IIB + cases with clinical progression. Due to local progression, NET was replaced by neoadjuvant chemotherapy in three patients (four tumors). In two postmenopausal patients, letrozole was replaced by tamoxifen because of the insufficient treatment effect. In 19/42 cases, breast-conserving surgery was performed. Within Group 1, there was no cancer in four cases, while only DCIS remained in 2 (pCR: 13 %); Groups 2 and 3 comprised 25 and 15 cases, respectively. The likeliness of a good response (Groups 1 and 2 vs. Group 3) to NET was increased by 7 % for every 1 % increase of the expression of ER (OR = 1.070; 95 % CI: 1.007–1.138, p = 0.029). Progression-free survival differed according to treatment response (p = 0.001). The post-therapy Ki67 value of ≤15 % had only a marginal effect on survival. No other associations were detected between the tumor characteristics and the therapeutic response or survival. Long-duration NET is effective and safe in cases of hormone-sensitive breast cancer.

Keywords

Breast cancer Hormone sensitivity Letrozole Tamoxifen Neoadjuvant endocrine therapy Predictive factors 

References

  1. 1.
    Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, Denkert C, Eiermann W, Gnant M, Harris JR, Karn T, Liedtke C, Mauri D, Rouzier R, Ruckhaeberle E, Semiglazov V, Symmans WF, Tutt A, Pusztai L (2012) Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol 19:1508–1516CrossRefPubMedGoogle Scholar
  2. 2.
    Fumagalli D, Bedard PL, Nahleh Z, Michiels S, Sotiriou C, Loi S, Sparano JA, Ellis M, Hylton N, Zujewski JA, Hudis C, Esserman L, Piccart M, BIG-NABCG collaboration (2012) A common language in neoadjuvant breast cancer clinical trials: proposals for standard definitions and endpoints. Lancet Oncol 13:e240–e248CrossRefPubMedGoogle Scholar
  3. 3.
    Hoffman KE, Mittendorf EA, Buchholz TA (2012) Optimising radiation treatment decisions for patients who receive neoadjuvant chemotherapy and mastectomy. Lancet Oncol 13:e270–e276CrossRefPubMedGoogle Scholar
  4. 4.
    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 (2013) Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol 31:3623–3630CrossRefGoogle Scholar
  5. 5.
    Prowell TM, Pazdur R (2012) Pathological complete response and accelerated drug approval in early breast cancer. N Engl J Med 366:2438–2441CrossRefPubMedGoogle Scholar
  6. 6.
    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 (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. doi: 10.1016/S0140-6736(13)62422-8 PubMedGoogle Scholar
  7. 7.
    Geisler J, Smith I, Miller W (2012) Presurgical (neoadjuvant) endocrine therapy is a useful model to predict response and outcome to endocrine treatment in breast cancer patients. J Steroid Biochem Mol Biol 131:93–100CrossRefPubMedGoogle Scholar
  8. 8.
    Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ, Panel members (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24:2206–2223PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Charehbili A, Fontein DB, Kroep JR, Liefers GJ, Mieog JS, Nortier JW, van de Velde CJ (2014) Neoadjuvant hormonal therapy for endocrine sensitive breast cancer: a systematic review. Cancer Treat Rev 40:86–92CrossRefPubMedGoogle Scholar
  10. 10.
    Chia YH, Ellis MJ, Ma CX (2010) Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool. Br J Cancer 103:759–764PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Barnadas A, Gil M, González S, Tusquets I, Muñoz M, Arcusa A, Prieto L, Margelí-Vila M, Moreno A (2009) Exemestane as primary treatment of oestrogen receptor-positive breast cancer in postmenopausal women: a phase II trial. Br J Cancer 100:442–449PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Toi M, Saji S, Masuda N, Kuroi K, Sato N, Takei H, Yamamoto Y, Ohno S, Yamashita H, Hisamatsu K, Aogi K, Iwata H, Takada M, Ueno T, Saji S, Chanplakorn N, Suzuki T, Sasano H (2011) Ki67 index changes, pathological response and clinical benefits in primary breast cancer patients treated with 24 weeks of aromatase inhibition. Cancer Sci 102:858–865CrossRefPubMedGoogle Scholar
  13. 13.
    Dixon JM, Renshaw L, Macaskill EJ, Young O, Murray J, Cameron D, Kerr GR, Evans DB, Miller WR (2009) Increase in response rate by prolonged treatment with neoadjuvant letrozole. Breast Cancer Res Treat 113:145–151CrossRefPubMedGoogle Scholar
  14. 14.
    Allevi G, Strina C, Andreis D, Zanoni V, Bazzola L, Bonardi S, Foroni C, Milani M, Cappelletti MR, Gussago F, Aguggini S, Giardini R, Martinotti M, Fox SB, Harris AL, Bottini A, Berruti A, Generali D (2013) Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer. Br J Cancer 108:1587–1592PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Hojo T, Kinoshita T, Imoto S, Shimizu C, Isaka H, Ito H, Imi K, Wada N, Ando M, Fujiwara Y (2013) Use of the neo-adjuvant exemestane in post-menopausal estrogen receptor-positive breast cancer: a randomized phase II trial (PTEX46) to investigate the optimal duration of preoperative endocrine therapy. Breast 22:263–267CrossRefPubMedGoogle Scholar
  16. 16.
    Montagna E, Cancello G, Colleoni M (2013) The aromatase inhibitors (plus ovarian function suppression) in premenopausal breast cancer patients: ready for prime time? Cancer Treat Rev 39:886–890CrossRefPubMedGoogle Scholar
  17. 17.
    Torrisi R, Bagnardi V, Rotmensz N, Scarano E, Iorfida M, Veronesi P, Luini A, Viale G, Santoro A, Colleoni M, Goldhirsch A (2011) Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer. Breast Cancer Res Treat 126:431–441CrossRefPubMedGoogle Scholar
  18. 18.
    Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214CrossRefPubMedGoogle Scholar
  19. 19.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology, College of American Pathologists (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145CrossRefPubMedGoogle Scholar
  20. 20.
    Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC, American Society of Clinical Oncology, College of American Pathologists (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med 134:e48–e72PubMedGoogle Scholar
  21. 21.
    Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T, McShane L, Paik S, Penault-Llorca F, Prudkin L, Regan M, Salter J, Sotiriou C, Smith IE, Viale G, Zujewski JA, Hayes DF, International Ki-67 in Breast Cancer Working Group (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103:1656–1664PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Ellis MJ, Tao Y, Luo J, A’Hern R, Evans DB, Bhatnagar AS, Chaudri Ross HA, von Kameke A, Miller WR, Smith I, Eiermann W, Dowsett M (2008) Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst 100:1380–1388PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Smith IE, Dowsett M, Ebbs SR, Dixon JM, Skene A, Blohmer JU, Ashley SE, Francis S, Boeddinghaus I, Walsh G, IMPACT Trialists Group (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 23:5108–5116CrossRefPubMedGoogle Scholar
  24. 24.
    DeCensi A, Guerrieri-Gonzaga A, Gandini S, Serrano D, Cazzaniga M, Mora S, Johansson H, Lien EA, Pruneri G, Viale G, Bonanni B (2011) Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer. Ann Oncol 22:582–587CrossRefPubMedGoogle Scholar
  25. 25.
    Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cussac A, Jänicke F, Miller WR, Evans DB, Dugan M, Brady C, Quebe-Fehling E, Borgs M (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 19:3808–3816PubMedGoogle Scholar
  26. 26.
    Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, Griffith C, Boeddinghaus I, Salter J, Detre S, Hills M, Ashley S, Francis S, Walsh G, A’Hern R (2008) Proliferation and apoptosis as markers of benefit in neoadjuvant endocrine therapy of breast cancer. Clin Cancer Res 12:1024s–1030sCrossRefGoogle Scholar
  27. 27.
    Mello-Grand M, Singh V, Ghimenti C, Scatolini M, Regolo L, Grosso E, Zambelli A, Da Prada GA, Villani L, Fregoni V, Baiardi P, Marsoni S, Miller WR, Costa A, Chiorino G (2010) Gene expression profiling and prediction of response to hormonal neoadjuvant treatment with anastrozole in surgically resectable breast cancer. Breast Cancer Res Treat 121:399–411CrossRefPubMedGoogle Scholar
  28. 28.
    Ueno T, Masuda N, Yamanaka T, Saji S, Kuroi K, Sato N, Takei H, Yamamoto Y, Ohno S, Yamashita H, Hisamatsu K, Aogi K, Iwata H, Sasano H, Toi M (2014) Evaluating the 21-gene assay Recurrence Score® as a predictor of clinical response to 24 weeks of neoadjuvant exemestane in estrogen receptor-positive breast cancer. Int J Clin Oncol 19:607–613CrossRefPubMedGoogle Scholar
  29. 29.
    Krainick-Strobel UE, Lichtenegger W, Wallwiener D, Tulusan AH, Jänicke F, Bastert G, Kiesel L, Wackwitz B, Paepke S (2008) Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: a phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy. BMC Cancer 8:62PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Carpenter R, Doughty JC, Cordiner C, Moss N, Gandhi A, Wilson C, Andrews C, Ellis G, Gui G, Skene AI (2014) Optimum duration of neoadjuvant letrozole to permit breast conserving surgery. Breast Cancer Res Treat 144:569–576CrossRefPubMedGoogle Scholar
  31. 31.
    Alba E, Calvo L, Albanell J, De la Haba JR, Arcusa Lanza A, Chacon JI, Sanchez-Rovira P, Plazaola A, Lopez Garcia-Asenjo JA, Bermejo B, Carrasco E, Lluch A (2012) GEICAM: Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study. Ann Oncol 23:3069–3074CrossRefPubMedGoogle Scholar
  32. 32.
    Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, Jakesz R, Seifert M, Hubalek M, Pristauz G, Bauernhofer T, Eidtmann H, Eiermann W, Steger G, Kwasny W, Dubsky P, Hochreiner G, Forsthuber EP, Fesl C, Greil R, Austrian Breast and Colorectal Cancer Study Group (2011) Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol 12:631–641CrossRefPubMedGoogle Scholar
  33. 33.
    Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA, TEXT and SOFT Investigators, International Breast Cancer Study Group: the TEXT and SOFT Investigators and the International Breast Cancer Study Group (2014) Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 371:107–118PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Debled M, Auxepaules G, de Lara CT, Garbay D, Brouste V, Bussières E, Mauriac L, Macgrogan G (2014) Neoadjuvant endocrine treatment in breast cancer: analysis of daily practice in large cancer center to facilitate decision making. Am J Surg. doi: 10.1016/j.amjsurg.2013.12.032 PubMedGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2015

Authors and Affiliations

  • Orsolya Rusz
    • 1
  • András Vörös
    • 2
  • Zoltán Varga
    • 1
  • Gyöngyi Kelemen
    • 1
  • Gabriella Uhercsák
    • 1
  • Alíz Nikolényi
    • 1
  • Katalin Ormándi
    • 3
    • 5
  • Zsolt Simonka
    • 4
  • Zsuzsanna Kahán
    • 1
    Email author
  1. 1.Department of OncotherapyUniversity of SzegedSzegedHungary
  2. 2.Department of PathologyUniversity of SzegedSzegedHungary
  3. 3.Department of RadiologyUniversity of SzegedSzegedHungary
  4. 4.Department of SurgeryUniversity of SzegedSzegedHungary
  5. 5.Diagnoscan Hungary Ltd.SzegedHungary

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