title: Randomized trial of preoperative docetaxel with or without capecitabine after 4 cycles of 5-fluorouracil– epirubicin–cyclophosphamide (FEC) in early-stage breast cancer: exploratory analyses identify Ki67 as a predictive biomarker for response to neoadjuvant chemotherapy.
abstract: This randomized, multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide (FEC) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker. Patients were randomized to 4 cycles of docetaxel/capecitabine (docetaxel: 75 mg/m2 on day 1; capecitabine: 1,650 mg/m2 on days 1–14 every 3 weeks) or docetaxel alone (75 mg/m2 on day 1 every 3 weeks) after completion of 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 every 3 weeks). The primary endpoint was the pathological complete response (pCR) rate. Predictive factor analysis was conducted using clinicopathological markers, including hormone receptors and Ki67 labeling index (Ki67LI). A total of 477 patients were randomized; the overall response in the docetaxel/capecitabine and docetaxel groups was 88.3 and 87.4 %, respectively. There were no significant differences in the pCR rate (docetaxel/capecitabine: 23 %; docetaxel: 24 %; p = 0.748), disease-free survival, or overall survival. However, patients with mid-range Ki67LI (10–20 %) showed a trend towards improved pCR rate with docetaxel/capecitabine compared to docetaxel alone. Furthermore, multivariate logistic regression analysis showed pre-treatment Ki67LI (odds ratio 1.031; 95 % CI 1.014–1.048; p = 0.0004) to be a significant predictor of pCR in this neoadjuvant treatment setting. Docetaxel/capecitabine (after 4 cycles of FEC) did not generate significant improvement in pCR compared to docetaxel alone. However, exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer.
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.forename: L W C
authors.initials: LW
authors.lastname: Chow
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Masuda
authors.forename: H
authors.initials: H
authors.lastname: Sasano
authors.forename: F
authors.initials: F
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Bando
authors.forename: H
authors.initials: H
authors.lastname: Iwata
authors.forename: T
authors.initials: T
authors.lastname: Morimoto
authors.forename: S
authors.initials: S
authors.lastname: Kamigaki
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Kuroi
authors.forename: K
authors.initials: K
authors.lastname: Aogi
authors.forename: M
authors.initials: M
authors.lastname: Kashiwaba
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
authors.forename: K
authors.initials: K
authors.lastname: Hisamatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Ueno
authors.forename: E
authors.initials: E
authors.lastname: Fakhrejahani
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Toi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D015251:Epirubicin; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011300:Preoperative Care; D011379:Prognosis; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D000069287:Capecitabine; D003520:Cyclophosphamide; D005472:Fluorouracil