title: Induction of apoptosis by tamoxifen and ICI 182780 in primary breast cancer.
abstract: Hormonal breast cancer therapies have traditionally been considered cytostatic, but recent pre-clinical data suggest that anti-oestrogens can induce apoptosis. The aim of this study was to assess whether tamoxifen (TAM) and ICI 182780 (ICI) could induce apoptosis in human breast cancer, and whether this was related to oestrogen receptor status. We measured apoptosis in primary breast cancer patients before and after pre-surgical treatment with 20 mg/day TAM (study 1) or 6 or 18 mg/day ICI (study 2). In each study there was a randomised non-treatment (NT) control group. TAM significantly increased apoptotic index (AI) in ER+ but not in ER- tumours. There was a significant increase in AI following treatment with ICI. Insufficient pairs of samples were available to determine whether this change was confined to ER+ tumours, but in a cross-sectional analysis AI was significantly higher in excision biopsies for ICI-treated than NT patients for ER+ but not ER- tumours. Our results provide clinical evidence that apoptosis may be induced in ER+ primary breast cancer by both non-steroidal and steroidal anti-oestrogens.
authors.affiliation: Department of Biochemical Endocrinology, Royal Marsden NHS Trust, London, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Ellis
authors.forename: G
authors.initials: G
authors.lastname: Saccani-Jotti
authors.forename: R
authors.initials: R
authors.lastname: Clarke
authors.forename: S R
authors.initials: SR
authors.lastname: Johnston
authors.forename: E
authors.initials: E
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Howell
authors.forename: R
authors.initials: R
authors.lastname: A'Hern
authors.forename: J
authors.initials: J
authors.lastname: Salter
authors.forename: S
authors.initials: S
authors.lastname: Detre
authors.forename: R
authors.initials: R
authors.lastname: Nicholson
authors.forename: J
authors.initials: J
authors.lastname: Robertson
authors.forename: I E
authors.initials: IE
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D003131:Combined Modality Therapy; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D016612:Paraffin Embedding; D010919:Placebos; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D010919:Placebos; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol