title: Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer.
abstract: PURPOSE The indications of adjuvant chemotherapy for patients with estrogen receptor (ER) -positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer. PATIENTS AND METHODS Expression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point. Results Ki67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71). CONCLUSION Ki67 expression identifies a subset of patients with ER-positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.
authors.affiliation: Department of Pathology, Centre Jean Perrin, EA 4233, Université d'Allvergne Clermont 1, Clermont-Ferrand 63000, France. frederique.penault-llorca@cjp.fr
authors.forename: Frédérique
authors.initials: F
authors.lastname: Penault-Llorca
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.forename: Christine
authors.initials: C
authors.lastname: Sagan
authors.forename: Magali
authors.initials: M
authors.lastname: Lacroix-Triki
authors.forename: Yves
authors.initials: Y
authors.lastname: Denoux
authors.forename: Veronique
authors.initials: V
authors.lastname: Verriele
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Baranzelli
authors.forename: Frederic
authors.initials: F
authors.lastname: Bibeau
authors.forename: Martine
authors.initials: M
authors.lastname: Antoine
authors.forename: Nicole
authors.initials: N
authors.lastname: Lagarde
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Martin
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D000077143:Docetaxel; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin