title: Cytotoxic and antiproliferative activity of the single agent epirubicin versus epirubicin plus tamoxifen as primary chemotherapy in human breast cancer: a single-institution phase III trial.
abstract: This study was designed to address whether simultaneous primary chemo-hormonal therapy provides additional activity compared with chemotherapy alone in breast cancer patients with operable or locally advanced disease. Between January 1997 and January 2002, 211 consecutive patients with T2-4, N0-1, M0 breast cancer were randomized to receive either epirubicin alone (EPI) or epirubicin plus tamoxifen (EPI-TAM). Ki67 expression was evaluated immunohistochemically in tumor specimens obtained before chemotherapy by incision biopsy and at definitive surgery. Tumor shrinkage of >50% was obtained in 76% of patients randomized in the EPI arm and 81.9% of patients randomized in the EPI-TAM arm (not significant). The corresponding rates of clinical and pathological complete response were 20.2 and 21.9% (not significant), and 4.8 and 6.7% (not significant), respectively. Pathologically complete response was more frequently observed in estrogen receptor (ER)-negative (ER-) tumors (P=0.04) and correlated with elevated baseline Ki67 expression (P<0.01). Both EPI and EPI-TAM treatments resulted in a significant reduction in Ki67 expression, either in overall patients (P=0.000) or in patients with ER+ breast cancer (P=0.000). The reduction in Ki67 immunostaining in the EPI-TAM arm was greater than in the EPI arm, leading to a lower Ki67 expression at post-operative residual histology (P=0.0041). The addition of tamoxifen to epirubicin chemotherapy did not improve the response rate but led to a significantly higher reduction in the Ki67 expression. Baseline elevated Ki67 expression and the ER- status were both associated with a greater chance of obtaining a pathological complete response at residual histology.
authors.affiliation: Breast Unit and Anatomia Patologica Azienda Ospedaliera Istituti Ospitalieri, Cremona, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Oncologia Medica, Azienda Ospedaliera San Luigi, Orbassano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bottini
authors.forename: A
authors.initials: A
authors.lastname: Berruti
authors.forename: M P
authors.initials: MP
authors.lastname: Brizzi
authors.forename: A
authors.initials: A
authors.lastname: Bersiga
authors.forename: D
authors.initials: D
authors.lastname: Generali
authors.forename: G
authors.initials: G
authors.lastname: Allevi
authors.forename: S
authors.initials: S
authors.lastname: Aguggini
authors.forename: G
authors.initials: G
authors.lastname: Bolsi
authors.forename: S
authors.initials: S
authors.lastname: Bonardi
authors.forename: B
authors.initials: B
authors.lastname: Tondelli
authors.forename: F
authors.initials: F
authors.lastname: Vana
authors.forename: M
authors.initials: M
authors.lastname: Tampellini
authors.forename: P
authors.initials: P
authors.lastname: Alquati
authors.forename: L
authors.initials: L
authors.lastname: Dogliotti
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019394:Ki-67 Antigen; D013629:Tamoxifen; D015251:Epirubicin