BRCA1/BRCA2 mutation status and analysis of cancer family history in participants of the Royal Marsden Hospital tamoxifen chemoprevention trial.
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.
Kote-Jarai
Zsofia
Z
Translational Cancer Genetics Team, Section of Cancer Genetics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. zsofia.kote-jarai@icr.ac.uk
Powles
Trevor J
TJ
Mitchell
Gillian
G
Tidy
Alwynne
A
Ashley
Sue
S
Easton
Douglas
D
Assersohn
Laura
L
Sodha
Nayanta
N
Salter
Janine
J
Gusterson
Barry
B
Dowsett
Mitch
M
Eeles
Rosalind
R
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*
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen