title: BRCA1/BRCA2 mutation status and analysis of cancer family history in participants of the Royal Marsden Hospital tamoxifen chemoprevention trial.
abstract: We have analysed the pedigrees of all 70 women who developed cancer in the Royal Marsden Hospital (RMH) tamoxifen chemoprevention trial, using the Claus model, to assess breast cancer susceptibility heterozygote risk (HR) and screened the entire coding regions of BRCA1 and 2 genes in 62 of these cases. We found a reduced incidence of breast cancers developing on tamoxifen in women who have a lower HR, but not in women with higher HR. There were too few BRCA1/2 mutations (4 cases) to be able to determine the efficacy of tamoxifen by BRCA status. Immunohistochemical analysis showed a significantly lower frequency of median ER (p=0.03) in the cancers developing in tamoxifen-treated patients. These results suggest that tamoxifen is less likely to be effective at reducing breast cancers which are ER negative and also in some individuals at higher HR.
authors.affiliation: Translational Cancer Genetics Team, Section of Cancer Genetics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. zsofia.kote-jarai@icr.ac.uk
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Powles
authors.forename: Gillian
authors.initials: G
authors.lastname: Mitchell
authors.forename: Alwynne
authors.initials: A
authors.lastname: Tidy
authors.forename: Sue
authors.initials: S
authors.lastname: Ashley
authors.forename: Douglas
authors.initials: D
authors.lastname: Easton
authors.forename: Laura
authors.initials: L
authors.lastname: Assersohn
authors.forename: Nayanta
authors.initials: N
authors.lastname: Sodha
authors.forename: Janine
authors.initials: J
authors.lastname: Salter
authors.forename: Barry
authors.initials: B
authors.lastname: Gusterson
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen