Breast Cancer Research and Treatment

, Volume 132, Issue 3, pp 853–861 | Cite as

The efficacy and safety of neoadjuvant chemotherapy +/− letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial

  • Mohammad Mohammadianpanah
  • Yaghoub Ashouri
  • Sare Hoseini
  • Niloofar Amadloo
  • Abdolrasoul Talei
  • Sedigheh Tahmasebi
  • Hamid Nasrolahi
  • Ahmad Mosalaei
  • Shapour Omidvari
  • Mansour Ansari
  • Mohammad Amin Mosleh-Shirazi
Clinical Trial

Abstract

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50–83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3–5) cycles of intravenous 5-fluorouracil 600 mg/m2, doxorubicin 60 mg/m2, and cyclophosphamide 600 mg/m2, every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

Keywords

Neoadjuvant chemotherapy Concurrent endocrine therapy Letrozole Locally advanced breast cancer Postmenopausal women 

References

  1. 1.
    Valero VV, Buzdar AU, Hortobagyi GN (1996) Locally advanced breast cancer. Oncologist 1:8–17PubMedGoogle Scholar
  2. 2.
    Giordano SH (2003) Update on locally advanced breast cancer. Oncologist 8:521–530PubMedCrossRefGoogle Scholar
  3. 3.
    Bergman L, van Dongen JA, van Ooijen B, van Leeuwen FE (1995) Should tamoxifen be a primary treatment choice for elderly breast cancer patients with locoregional disease? Breast Cancer Res Treat 34:77–83PubMedCrossRefGoogle Scholar
  4. 4.
    Chakrabarti J, Kenny FS, Syed BM, Robertson JF, Blamey RW, Cheung KL (2011) A randomised trial of mastectomy only versus tamoxifen for treating elderly patients with operable primary breast cancer-final results at 20-year follow-up. Crit Rev Oncol Hematol 78:260–264PubMedCrossRefGoogle Scholar
  5. 5.
    Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J, Mauriac L, Ellis M, Lassus M, Chaudri-Ross HA, Dugan M, Borgs M (2001) Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol 12:1527–1532PubMedCrossRefGoogle Scholar
  6. 6.
    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 23:5108–5116PubMedCrossRefGoogle Scholar
  7. 7.
    Cataliotti L, Buzdar AU, Noguchi S, Bines J, Takatsuka Y, Petrakova K, Dube P, de Oliveira CT (2006) Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the pre-operative ‘Arimidex’ compared to tamoxifen (PROACT) trial. Cancer 106:2095–2103PubMedCrossRefGoogle Scholar
  8. 8.
    Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, Parker JS, Luo J, DeSchryver K, Allred DC, Esserman LJ, Unzeitig GW, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Watson MA, Leitch M, Hunt K, Olson JA (2011) Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2–3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype–ACOSOG Z1031. J Clin Oncol 29:2342–2349PubMedCrossRefGoogle Scholar
  9. 9.
    Mouridsen H, Gershanovich M, Sun Y, Pérez-Carrión R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jänicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M (2001) Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the international letrozole breast cancer group. J Clin Oncol 19:2596–2606PubMedGoogle Scholar
  10. 10.
    Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, Melnikova OA, Paltuev RM, Kletzel A, Berstein LM (2007) Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer 110:244–254PubMedCrossRefGoogle Scholar
  11. 11.
    Alba E, Calvo L, Albanell J, De la Haba J, Chacon J, Arcusa Lanza A, Sanchez Rovira P, Plazaola A, Lopez Garcia-Asenjo J, Lluch A, on behalf of GEICAM (2010) Chemotherapy (CT) versus hormone therapy (HT) as neoadjuvant treatment in luminal breast cancer: a multicenter, randomized phase II study (GEICAM/2006–03). J Clin Oncol 28:15s abstract 500Google Scholar
  12. 12.
    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 11:1081–1088. doi:10.1634/theoncologist.11-10-1081 PubMedCrossRefGoogle Scholar
  13. 13.
    Pritchard KI (2008) Combining endocrine agents with chemotherapy: which patients and what sequence? Cancer 112:718–722. doi:10.1002/cncr.23189 PubMedCrossRefGoogle Scholar
  14. 14.
    Watanabe N, Ootawa Y, Kodama K, Kaide A, Ootsuka N, Matsuoka J (2010) Concurrent administration of chemo-endocrine therapy for postmenopausal breast cancer patients. Breast Cancer 17(4):247–253. doi:10.1007/s12282-009-0144-6 PubMedCrossRefGoogle Scholar
  15. 15.
    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 92:205–216PubMedCrossRefGoogle Scholar
  16. 16.
    Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, Blohmer JU, Eiermann W, Jackesz R, Jonat W, Lebeau A, Loibl S, Miller W, Seeber S, Semiglazov V, Smith R, Souchon R, Stearns V, Untch M, von Minckwitz G (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. doi:10.1200/JCO.2005.02.6187 PubMedCrossRefGoogle Scholar
  17. 17.
    Chia S, Swain SM, Byrd DR, Mankoff DA (2008) Locally advanced and inflammatory breast cancer. J Clin Oncol 26:786–790PubMedCrossRefGoogle Scholar
  18. 18.
    Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, Blohmer JU, Eiermann W, Jackesz R, Jonat W, Lebeau A, Loibl S, Miller W, Seeber S, Semiglazov V, Smith R, Souchon R, Stearns V, Untch M, von Minckwitz G (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; Erratum in: J Clin Oncol 2006;24:3221PubMedCrossRefGoogle Scholar
  19. 19.
    Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, Melnikova OA, Paltuev RM, Kletzel A, Berstein LM (2007) Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer 110(2):244–254PubMedCrossRefGoogle Scholar
  20. 20.
    Gnant M, Harbeck N, Thomssen C (2011) St. Gallen 2011: summary of the consensus discussion. Breast Care (Basel) 6(2):136–141CrossRefGoogle Scholar
  21. 21.
    Chia S, Swain SM, Byrd DR, Mankoff DA (2008) Locally advanced and inflammatory breast cancer. J Clin Oncol 26:786–790. doi:10.1200/JCO.2008.15.0243 PubMedCrossRefGoogle Scholar
  22. 22.
    Rouzier R, Pusztai L, Delaloge S, Gonzalez-Angulo AM, Andre F, Hess KR, Buzdar AU, Garbay JR, Spielmann M, Mathieu MC, Symmans WF, Wagner P, Atallah D, Valero V, Berry DA, Hortobagyi GN (2005) Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer. J Clin Oncol 23:8331–8339. doi:10.1200/JCO.2005.01.2898 PubMedCrossRefGoogle Scholar
  23. 23.
    Ross JS, Linette GP, Stec J, Clark E, Ayers M, Leschly N, Symmans WF, Hortobagyi GN, Pusztai L (2004) Breast cancer biomarkers and molecular medicine: part II. Expert Rev Mol Diagn 4:169–188. doi:10.1586/14737159.4.2.169 PubMedCrossRefGoogle Scholar
  24. 24.
    Bast RC Jr, Ravdin P, Hayes DF, Bates S, Fritsche H Jr, Jessup JM, Kemeny N, Locker GY, Mennel RG, Somerfield MR (2001) 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American society of clinical oncology. J Clin Oncol 19:1865–1878PubMedGoogle Scholar
  25. 25.
    Gibson L, Lawrence D, Dawson C, Bliss J (2009) Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev: CD003370. doi:10.1002/14651858.CD003370.pub3
  26. 26.
    Torrisi R, Dellapasqua S, Ghisini R, Viale G, Veronesi P, Luini A, Intra M, Peruzzotti G, Rocca A, Balduzzi A, Cardillo A, Goldhirsch A, Colleoni M (2008) Preoperative concurrent chemo- and endocrine therapies for women with large operable breast cancer expressing steroid hormone receptors. Breast 17:654–660. doi:10.1016/j.breast.2008.05.002 PubMedCrossRefGoogle Scholar
  27. 27.
    Cohen MH, Johnson JR, Li N, Chen G, Pazdur R (2002) Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer. Clin Cancer Res 8:665–669PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Mohammad Mohammadianpanah
    • 1
  • Yaghoub Ashouri
    • 1
  • Sare Hoseini
    • 1
  • Niloofar Amadloo
    • 1
  • Abdolrasoul Talei
    • 2
  • Sedigheh Tahmasebi
    • 2
  • Hamid Nasrolahi
    • 1
  • Ahmad Mosalaei
    • 1
  • Shapour Omidvari
    • 1
  • Mansour Ansari
    • 1
  • Mohammad Amin Mosleh-Shirazi
    • 1
    • 3
  1. 1.Department of Radiation Oncology, Cancer Research CenterNamazi Hospital, Shiraz University of Medical SciencesShirazIran
  2. 2.Department of SurgeryShahid Faghihi Hospital, Shiraz University of Medical SciencesShirazIran
  3. 3.Center for Research in Medical Physics and Biomedical EngineeringShiraz University of Medical SciencesShirazIran

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