title: Proliferation and apoptosis as markers of benefit in neoadjuvant endocrine therapy of breast cancer.
abstract: The study of changes in proliferation as a marker of treatment benefit during presurgical endocrine treatment of breast cancer has become increasingly popular, particularly using the nuclear marker Ki67, and holds the potential for prioritizing new treatments for full clinical development. There are weakly significant relationships between Ki67 change and clinical response that differ according to data handling. In the neoadjuvant Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen trial, suppression of Ki67 at both 2 and 12 weeks was greater with the aromatase inhibitor anastrozole than with either tamoxifen or the combination of anastrozole and tamoxifen. We report here that absolute values of Ki67 after 2 weeks were also significantly lower with anastrozole than with tamoxifen and the combination. This indicates that it may be possible to make such comparisons using surgical samples only. We argue that these changes in proliferation and concurrent changes in apoptosis may be expected to be more predictive of adjuvant benefit from endocrine therapy than clinical response.
authors.affiliation: Academic Department of Biochemistry and Breast Unit, Royal Marsden Hospital, London SW3 6JJ, United Kingdom. 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: Steve 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: Clive
authors.initials: C
authors.lastname: Griffith
authors.forename: Irene
authors.initials: I
authors.lastname: Boeddinghaus
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: Susan
authors.initials: S
authors.lastname: Ashley
authors.forename: Stephen
authors.initials: S
authors.lastname: Francis
authors.forename: Geraldine
authors.initials: G
authors.lastname: Walsh
authors.forename: Roger
authors.initials: R
authors.lastname: A'Hern
mesh_terms: D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D020360:Neoadjuvant Therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D009570:Nitriles / Q000627:therapeutic use; D011379:Prognosis; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole