title: Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer.
abstract: Tumor expression of the proliferation antigen Ki67 is widely used to assess the prognosis of cancer patients. A change in the expression of Ki67 after short-term exposure of patients to therapeutic agents is frequently used as a pharmacodynamic marker of efficacy, particularly among breast cancer patients before undergoing surgery. To determine the clinical significance of the level of tumor cell proliferation during endocrine therapy for breast cancer, we measured the expression of Ki67 in tumor biopsy samples taken before and after 2 weeks of presurgical treatment with anastrozole or tamoxifen or the combination of anastrozole plus tamoxifen in 158 patients with hormone receptor-positive primary disease. In a multivariable analysis, we found that higher Ki67 expression after 2 weeks of endocrine therapy was statistically significantly associated with lower recurrence-free survival (P = .004) whereas higher Ki67 expression at baseline was not. Larger baseline tumor size and lower estrogen receptor level after 2 weeks of treatment were also statistically significantly associated with poorer recurrence-free survival (P < .001 and P = .04, respectively). Our data indicate that measurements of tumor Ki67 level after short-term endocrine treatment may improve the prediction of recurrence-free survival by integrating the prognostic value of Ki67 level at baseline with changes in Ki67 level that are associated with treatment benefit.
authors.affiliation: Academic Department of Biochemistry, 4th Floor, Wallace Wing, The Royal Marsden Hospital, Fulham Road, London SW3 6 JJ, UK. mitch.dowsett@icr.ac.uk
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Ian E
authors.initials: IE
authors.lastname: Smith
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Ebbs
authors.forename: J Michael
authors.initials: JM
authors.lastname: Dixon
authors.forename: Anthony
authors.initials: A
authors.lastname: Skene
authors.forename: Roger
authors.initials: R
authors.lastname: A'Hern
authors.forename: Janine
authors.initials: J
authors.lastname: Salter
authors.forename: Simone
authors.initials: S
authors.lastname: Detre
authors.forename: Margaret
authors.initials: M
authors.lastname: Hills
authors.forename: Geraldine
authors.initials: G
authors.lastname: Walsh
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000379:methods*; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D009570:Nitriles / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis; D018401:Sample Size; D013629:Tamoxifen / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole