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dc.contributor.authorBramley, M
dc.contributor.authorClarke, Robert B
dc.contributor.authorHowell, Anthony
dc.contributor.authorEvans, D Gareth R
dc.contributor.authorArmer, T
dc.contributor.authorBaildam, Andrew D
dc.contributor.authorAnderson, Elizabeth
dc.date.accessioned2009-07-06T12:10:17Z
dc.date.available2009-07-06T12:10:17Z
dc.date.issued2006-04-10
dc.identifier.citationEffects of oestrogens and anti-oestrogens on normal breast tissue from women bearing BRCA1 and BRCA2 mutations. 2006, 94 (7):1021-8 Br. J. Canceren
dc.identifier.issn0007-0920
dc.identifier.pmid16538216
dc.identifier.doi10.1038/sj.bjc.6603042
dc.identifier.urihttp://hdl.handle.net/10541/72560
dc.description.abstractThere is considerable interest in whether anti-oestrogens can be used to prevent breast cancer in women bearing mutations in the BRCA1 and BRCA2 genes. The effects of oestradiol (E2), tamoxifen (TAM) and fulvestrant (FUL) on proliferation and steroid receptor expression were assessed in normal breast epithelium taken from women at varying risks of breast cancer and implanted into athymic nude mice, which were treated with E2 in the presence and absence of TAM or FUL. Tissue samples were taken at various time points thereafter for assessment of proliferative activity and expression of oestrogen and progesterone receptors (ERalpha and PgR) by immunohistochemistry. Oestradiol increased proliferation in the breast epithelium from women carrying mutations in the BRCA1/2 genes, those otherwise at increased risk and those at population risk of breast cancer. This increase was reduced by both TAM and FUL in all risk groups. In the absence of E2, PgR expression was reduced in all risk groups but significantly more so in the BRCA-mutated groups. Subsequent E2 treatment caused a rapid, complete induction of PgR expression in the population-risk group but not in the high-risk or BRCA-mutated groups in which PgR induction was significantly delayed. These data suggest that the mechanisms by which E2 induces breast epithelial PgR expression are impaired in BRCA1/2 mutation carriers, whereas those regulating proliferation remain intact. We conclude that early anti-oestrogen treatment should prevent breast cancer in very high-risk women.
dc.language.isoenen
dc.subjectBreast Canceren
dc.subject.meshAdolescent
dc.subject.meshAdult
dc.subject.meshBreast
dc.subject.meshBreast Neoplasms
dc.subject.meshCell Proliferation
dc.subject.meshEstradiol
dc.subject.meshEstrogen Antagonists
dc.subject.meshEstrogen Receptor alpha
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation
dc.subject.meshGenes, BRCA1
dc.subject.meshGenes, BRCA2
dc.subject.meshHumans
dc.subject.meshMiddle Aged
dc.subject.meshMutation
dc.subject.meshReceptors, Progesterone
dc.subject.meshRisk Factors
dc.subject.meshTamoxifen
dc.titleEffects of oestrogens and anti-oestrogens on normal breast tissue from women bearing BRCA1 and BRCA2 mutations.en
dc.typeArticleen
dc.contributor.departmentDepartment of Surgery, Christie Hospital NHS Trust, Manchester M20 4BX, USA.en
dc.identifier.journalBritish Journal of Canceren
html.description.abstractThere is considerable interest in whether anti-oestrogens can be used to prevent breast cancer in women bearing mutations in the BRCA1 and BRCA2 genes. The effects of oestradiol (E2), tamoxifen (TAM) and fulvestrant (FUL) on proliferation and steroid receptor expression were assessed in normal breast epithelium taken from women at varying risks of breast cancer and implanted into athymic nude mice, which were treated with E2 in the presence and absence of TAM or FUL. Tissue samples were taken at various time points thereafter for assessment of proliferative activity and expression of oestrogen and progesterone receptors (ERalpha and PgR) by immunohistochemistry. Oestradiol increased proliferation in the breast epithelium from women carrying mutations in the BRCA1/2 genes, those otherwise at increased risk and those at population risk of breast cancer. This increase was reduced by both TAM and FUL in all risk groups. In the absence of E2, PgR expression was reduced in all risk groups but significantly more so in the BRCA-mutated groups. Subsequent E2 treatment caused a rapid, complete induction of PgR expression in the population-risk group but not in the high-risk or BRCA-mutated groups in which PgR induction was significantly delayed. These data suggest that the mechanisms by which E2 induces breast epithelial PgR expression are impaired in BRCA1/2 mutation carriers, whereas those regulating proliferation remain intact. We conclude that early anti-oestrogen treatment should prevent breast cancer in very high-risk women.


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