title: DCIS and aromatase inhibitors.
abstract: In patients with hormone receptor positive DCIS tamoxifen reduces recurrence rates by almost 50%. Few data are available with aromatase inhibitors from randomised studies. In the ATAC study there were three DCIS lesions in the anastrozole arm and four in the tamoxifen arm in the women with ER positive invasive cancer. In the MA17 study which randomised patients to up to 5 years of letrozole or placebo there was only one DCIS event in the contralateral breast in patients taking letrozole and five on placebo. There were also four patients in this study who had DCIS in the conserved breast on placebo and none in the letrozole treated group. The few clinical data that are available therefore suggest the aromatase inhibitors are likely to be effective in DCIS. A histological review of a study of 206 postmenopausal women with invasive oestrogen receptor positive breast cancer who were randomised as part of a 14 day preoperative study to receive 2.5mg of letrozole or 1mg of anastrozole identified 27 patients with 28 pairs of tumours in whom there was sufficient ER positive DCIS in invasive cancer in the initial core biopsy and in the subsequent surgery specimen, to evaluate for PgR activity and proliferation. Within the DCIS both aromatase inhibitors significantly reduced PgR expression and both drugs also produced a significant fall in proliferation. There was a moderate degree of agreement between the fall in PgR in both the invasive cancer and DCIS (Kappa=0.5; p=0.0013) and between the fall in proliferation and between the invasive and in situ components (correlation coefficient=0.68; p<0.001). This study has shown significant effects of aromatase inhibitors on DCIS indicating that these agents are therapeutically active in this condition.
authors.affiliation: Edinburgh Breast Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom. jmd@ed.ac.uk
authors.forename: J Michael
authors.initials: JM
authors.lastname: Dixon
authors.forename: Dana
authors.initials: D
authors.lastname: Faratian
authors.forename: Sharon
authors.initials: S
authors.lastname: White
authors.forename: Lorna
authors.initials: L
authors.lastname: Renshaw
authors.forename: Juliette
authors.initials: J
authors.lastname: Murray
authors.forename: Oliver
authors.initials: O
authors.lastname: Young
authors.forename: E Jane
authors.initials: EJ
authors.lastname: Macaskill
authors.forename: Linda
authors.initials: L
authors.lastname: Williams
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thomas
authors.forename: Dean B
authors.initials: DB
authors.lastname: Evans
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D000077289:Letrozole; D009361:Neoplasm Invasiveness; D009570:Nitriles / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000277:Adjuvants, Pharmaceutic; D000077384:Anastrozole; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D000077289:Letrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles