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Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers

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Summary

Purpose

In the adjuvant setting, taxanes modestly improve clinical outcome and survival. The goal of the present study was to define the efficacy of neoadjuvant docetaxel in treatment-naïve large, locally advanced breast cancers and to better understand docetaxel’s mechanism of action by evaluating biomarker modulation in response to treatment.

Patients and methods

Fifty-one patients were enrolled. Patients received four cycles of docetaxel (100 mg/m2 q3weeks) followed by surgery and four cycles of doxorubicin and cyclophosphamide (60/600 mg/m2 q3weeks). Radiation and hormonal therapy were given if clinically indicated. Clinical responses were assessed at completion of neoadjuvant docetaxel. Pathological responses were considered complete (pCR) if no tumor cells were identified in the surgical specimen or near complete (npCR) if only occasional scattered tumor cells were seen. Proliferation (Ki-67) and apoptosis (cleaved caspase-3) were measured by IHC in tissue obtained at baseline and at surgery.

Results

The median tumor size was 9 cm (range 4–30 cm). Objective response rate was 75% with clinical complete response in 27%, partial response in 48%, and stable disease in 25% of the patients. pCR/npCR was reported in 20% of patients. With a median follow up of 28 months, 98 and 78% of the patients were alive at 12 and 24 months, respectively. Overall survival at 24 months was significantly better in patients who achieved a clinical response, 85 versus 51%, p=0.008, but pCR/npCR was not a significant predictor of outcome. Apoptosis was induced in clinical responders (p=0.002), while the proliferation index did not change significantly. In patients who had no clinical response to docetaxel, neither apoptosis nor proliferation changed significantly.

Conclusion

Neoadjuvant single agent docetaxel is effective in treating patients with large locally advanced breast cancer and clinical response is associated with improved survival. Docetaxel acts therapeutically by inducing apoptosis and this can be used as a marker of response.

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References

  1. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Early Breast Cancer Trialists’ Collaborative Group. Lancet 339: 1–15, 1992

    Google Scholar 

  2. Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 352: 930–42, 1998

  3. Hortobagyi GN,: Comprehensive management of locally advanced breast cancer. Cancer 66:1387–1391, 1990

    Article  PubMed  CAS  Google Scholar 

  4. Hortobagyi GN, Ames FC, Buzdar AU, Kau SW, McNeese MD, Paulus D, Hug V, Holmes FA, Romsdahl MM, Fraschini G, et al. :Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy Cancer 62:2507–2516, 1988

    Article  PubMed  CAS  Google Scholar 

  5. Fisher B, Gunduz N, Saffer EA,:Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases Cancer Res 43:1488–1492, 1983

    PubMed  CAS  Google Scholar 

  6. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB, Jr., Hoehn JL, Lees AW, Dimitrov NV, Bear HD,: Effect of preoperative chemotherapy on the outcome of women with operable breast cancer J Clin Oncol 16:2672–2685, 1998

    PubMed  CAS  Google Scholar 

  7. Goble S, Bear HD,: Emerging role of taxanes in adjuvant and neoadjuvant therapy for breast cancer: the potential and the questions Surg Clin North Am 83:943–971, 2003

    Article  PubMed  Google Scholar 

  8. Hutcheon AW, Heys SD, Sarkar TK, Ogston KN, Eremin O, Walker LG, Miller ID,: Docetaxel primary chemotherapy in breast cancer: a five year update of the Aberdeen trial Breast Cancer Res Treat 82:S9, 2003

    Google Scholar 

  9. Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Elledge R, Mohsin S, Osborne CK, Chamness GC, Allred DC, O’Connell P,: Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer Lancet 362:362–369, 2003

    Article  PubMed  CAS  Google Scholar 

  10. Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E, 3rd, Schilsky RL, Wood WC, Muss HB, Norton L,: Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer J Clin Oncol 21:976–983, 2003

    Article  PubMed  CAS  Google Scholar 

  11. Nabholtz JM, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Vogel C, Weaver C, Walley B, Martin M, Chap L, Tomiak E, Juhos E, Guevin R, Howell A, Hainsworth J, Fornander T, Blitz S, Gazel S, Loret C, Riva A,: Phase III trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer (BC) patients: interim analysis of the BCIRG 001 study Proc Am Soc Clin Oncol 21:36a, 2002

    Google Scholar 

  12. Valero V,: Docetaxel as single-agent therapy in metastatic breast cancer: clinical efficacy. Semin Oncol 24:S13-11–S13-18, 1997

    Google Scholar 

  13. Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN,: Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel J Clin Oncol 20:1456–1466, 2002

    Article  PubMed  CAS  Google Scholar 

  14. von Minckwitz G, Raab G, Schuette M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, Lampe W, Jackisch C, duBois A, Caputo A, Kaufmann Jr. M,: Dose-dense versus sequential adriamcycin/docetaxel combination as preoperative chemotherapy (pCHT) in operable breast cancer (T2-3, N0-2,M0) – primary endpoint analysis of the GEPARDUO-Study Proc Am Soc Clin Oncol 21:43a, 2002

    Google Scholar 

  15. Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N,: The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27 J Clin Oncol 21:4165–4174, 2003

    Article  PubMed  CAS  Google Scholar 

  16. Vinholes J, Bouzid K, Salas F, Mickiewicz E, Valdivia S, Ostapenko V, Ghilezan N, Blanc C,: Preliminary results of a multicentre phase III trial of taxotere and doxorubicin (AT) versus 5-Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) in patients (Pts) with Unresectable Locally Advanced Breast Cancer (ULABC) Proc Am Soc Clin Oncol 20:26a, 2001

    Google Scholar 

  17. Luporsi E, Vanlemmens L, Coudert B, Mayer F, Bonneterre J, Petit T, Borel C, Hirsch M, Bey P,: 6 Cycles of FEC 100 vs 6 cycles of Epirubicin-Docetaxel (ED) as neoadjuvant chemotherapy in operable breast cancer patients (Pts): preliminary results of a randomized phase II trial of Girec S01 Proc Am Soc Clin Oncol 19:92a, 2000

    Google Scholar 

  18. Gradishar WJ,: Docetaxel as neoadjuvant chemotherapy in patients with stage III breast cancer. Oncology (Huntingt) 11:15–18, 1997

    CAS  Google Scholar 

  19. Amat S, Bougnoux P, Penault-Llorca F, Fetissof F, Cure H, Kwiatkowski F, Achard JL, Body G, Dauplat J, Chollet P,: Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate Br J Cancer 88:1339–1345, 2003

    Article  PubMed  CAS  Google Scholar 

  20. Hutcheon AW, Heys SD, Sarkar TK,: Neoadjuvant docetaxel in locally advanced breast cancer Breast Cancer Res Treat 79(Suppl 1):S19–S24, 2003

    Article  PubMed  CAS  Google Scholar 

  21. Evans TRJ, Gould E, Foster E, Crown JP, Leonard RCF, Mansi JL,: Phase III randomised trial of adriamycin (A) and docetaxel (D) versus A and cyclophosphamide (C) as primary medical therapy (PMT) in women with breast cancer: an ACCOG study Proc Am Soc Clin Oncol 21:35a, 2002

    Google Scholar 

  22. Herbst RS, Khuri FR: Mode of action of docetaxel  – a basis for combination with novel anticancer agents Cancer Treat Rev 29:407–415, 2003

    Article  PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  24. 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

    PubMed  CAS  Google Scholar 

  25. Chang J, Ormerod M, Powles TJ, Allred DC, Ashley SE, Dowsett M,: Apoptosis and proliferation as predictors of chemotherapy response in patients with breast carcinoma Cancer 89:2145–2152, 2000

    Article  PubMed  CAS  Google Scholar 

  26. Parton M, Krajewski S, Smith I, Krajewska M, Archer C, Naito M, Ahern R, Reed J, Dowsett M,: Coordinate expression of apoptosis-associated proteins in human breast cancer before and during chemotherapy Clin Cancer Res 8:2100–2108, 2002

    PubMed  CAS  Google Scholar 

  27. Ellis PA, Smith IE, Detre S, Burton SA, Salter J, A’Hern R, Walsh G, Johnston SR, Dowsett M,: Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer following preoperative chemotherapy Breast Cancer Res Treat 48:107–116, 1998

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Supported in part by Aventis, Inc., Breast Cancer Research Foundation and Emma Jacobs Research Fund.

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Authors and Affiliations

  1. Breast Center and the Departments of Medicine, Pathology, and Molecular and Cellular Biology, Baylor College of Medicine and the Methodist Hospital, Houston, TX, 77030 , USA

    Yee-Lu Tham, L. Fernando Gomez, Syed Mohsin, M. Carolina Gutierrez, Heidi Weiss, Susan G. Hilsenbeck, Richard M. Elledge, Gary C. Chamness, C. Kent Osborne, D. Craig Allred & Jenny C. Chang

  2. Breast Center, Baylor College of Medicine and the Methodist Hospital, 1 Baylor Plaza, Houston, TX, 77030, USA

    Jenny C. Chang

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  1. Yee-Lu Tham
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  2. L. Fernando Gomez
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  3. Syed Mohsin
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  4. M. Carolina Gutierrez
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  6. Susan G. Hilsenbeck
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  11. Jenny C. Chang
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Correspondence to Jenny C. Chang.

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Address for offprints and correspondence: Jenny Chang, Breast Center, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA; Tel.: +1-713-798-1905; Fax: +1-713-798-1642; E-mail: jcchang@breastcenter.tmc.edu

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Tham, YL., Gomez, L.F., Mohsin, S. et al. Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers. Breast Cancer Res Treat 94, 279–284 (2005). https://doi.org/10.1007/s10549-005-9020-z

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