title: Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer.
abstract: We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab.
  
  
  BACKGROUND
  Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer.
  
  
  METHODS
  We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety.
  
  
  RESULTS
  Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with estrogen receptor-positive and -negative cancer, respectively. Of all the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; only 1 patient required a dose reduction for nab-PTX because of peripheral neuropathy.
  
  
  CONCLUSIONS
  Neoadjuvant therapy using this combination appears to be effective and safe.
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka Medical College Hospital, Osaka, Japan. Electronic address: sur112@poh.osaka-med.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka Medical College Hospital, Osaka, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Iwamoto
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka Medical College Hospital, Osaka, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Breast Surgery, Osaka Rosai Hospital, Osaka, Japan.
authors.forename: Nobuki
authors.initials: N
authors.lastname: Matsunami
authors.affiliation: Department of Breast Surgery, Osaka Rosai Hospital, Osaka, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Morishima
authors.affiliation: Department of Breast Surgery, Osaka Police Hospital, Osaka, Japan.
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Yoshidome
authors.affiliation: Department of Breast Surgery, Yao Municipal Hospital, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Breast Surgery, Yao Municipal Hospital, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Morimoto
authors.affiliation: Department of Breast Surgery, Kansai Medical University Takii Hospital, Osaka, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Yamamoto
authors.affiliation: Department of Breast Surgery, Kansai Medical University Takii Hospital, Osaka, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tsubota
authors.affiliation: Department of Breast Surgery, Takatsuki Red Cross Hospital, Osaka, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka Medical College Hospital, Osaka, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Uchiyama
mesh_terms: D000328:Adult; D000368:Aged; D000068196:Albumin-Bound Paclitaxel / Q000627:therapeutic use*; D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D053758:Nanoparticles / Q000627:therapeutic use*; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000068196:Albumin-Bound Paclitaxel; D018943:Anthracyclines; D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Human epidermal growth factor receptor 2; Nanoparticle albumin-bound paclitaxel; Neoadjuvant chemotherapy; Pathologic complete response; Trastuzumab