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

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)279-284
Number of pages6
JournalBreast Cancer Research and Treatment
Volume94
Issue number3
DOIs
StatePublished - Dec 2005
Externally publishedYes

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docetaxel
Breast Neoplasms
Apoptosis
Survival
Taxoids
Neoplasms

Keywords

  • Apoptosis
  • Breast cancer
  • Docetaxel
  • Locally advanced
  • Neoadjuvant

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers. / Tham, Yee Lu; Gomez, L. Fernando; Mohsin, Syed; Gutierrez, M. Carolina; Weiss, Heidi; Hilsenbeck, Susan G.; Elledge, Richard M; Chamness, Gary C.; Osborne, C. Kent; Allred, D. Craig; Chang, Jenny C.

In: Breast Cancer Research and Treatment, Vol. 94, No. 3, 12.2005, p. 279-284.

Research output: Contribution to journalArticle

Tham, YL, Gomez, LF, Mohsin, S, Gutierrez, MC, Weiss, H, Hilsenbeck, SG, Elledge, RM, Chamness, GC, Osborne, CK, Allred, DC & Chang, JC 2005, 'Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers', Breast Cancer Research and Treatment, vol. 94, no. 3, pp. 279-284. https://doi.org/10.1007/s10549-005-9020-z
Tham, Yee Lu ; Gomez, L. Fernando ; Mohsin, Syed ; Gutierrez, M. Carolina ; Weiss, Heidi ; Hilsenbeck, Susan G. ; Elledge, Richard M ; Chamness, Gary C. ; Osborne, C. Kent ; Allred, D. Craig ; Chang, Jenny C. / Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers. In: Breast Cancer Research and Treatment. 2005 ; Vol. 94, No. 3. pp. 279-284.
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abstract = "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-na{\"i}ve 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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AU - Tham, Yee Lu

AU - Gomez, L. Fernando

AU - Mohsin, Syed

AU - Gutierrez, M. Carolina

AU - Weiss, Heidi

AU - Hilsenbeck, Susan G.

AU - Elledge, Richard M

AU - Chamness, Gary C.

AU - Osborne, C. Kent

AU - Allred, D. Craig

AU - Chang, Jenny C.

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N2 - 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.

AB - 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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