Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, <i>BRCA</i> mutations and oophorectomy

Møller, Pål; Borg, Åke; Evans, D. Gareth; Haites, Neva Elizabeth; Reis, Marta M.; Vasen, Hans F. A.; Anderson, Elaine; Steel, C. M.; Apold, Jaran; Goudie, David; Howell, Anthony; Lalloo, Fiona; Mæhle, Lovise; Gregory, Helen; Heimdal, Ketil

doi:10.1002/ijc.10641

Cited by 102 publications

(66 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Taken together, these observations suggest that while estrogenic pathways may act as an initial stimulus for abnormal proliferation, cancer progression may be maintained by ERaindependent mechanisms. This is consistent with observations made in BRCA1-related human breast cancer in which ovariectomy is protective, but the majority of cancers that develop are ERa negative (Kauff et al, 2002;Moller et al, 2002;Rebbeck et al, 2002;Foulkes et al, 2004).…”

Section: Discussionsupporting

confidence: 91%

Promotion of mammary cancer development by tamoxifen in a mouse model of Brca1-mutation-related breast cancer

Jones

Halama

et al. 2005

Oncogene

View full text Add to dashboard Cite

Loss of full-length Brca1 in mammary epithelial cells of the mouse mammary tumor virus (MMTV)-Cre Brca1 conditional exon 11 deletion mouse model results in the development of mammary adenocarcinomas with similar genetic changes to those found in human BRCA1-mutation-related breast cancers. We used this experimental model to evaluate the chemopreventive effect of tamoxifen on the development of mammary preneoplasia and adenocarcinoma. No protective effects of tamoxifen administration on mammary cancer development were found. Instead, tamoxifen treatment significantly increased rates of mammary epithelial cell proliferation and the prevalence of mammary hyperplasia at 6 months of age. Tamoxifen-exposed mice developed adenocarcinomas at younger ages than control mice and a higher percentage of mice developed adenocarcinomas by 12 months of age. Both whole mouse and tissue culture cell models were used to test if loss of full-length Brca1 was associated with a relative increase in the agonist activity of tamoxifen. Tamoxifen induced increased ductal growth in MMTV-Cre Brca1 conditional mice compared to wild type. Estrogen receptor alpha (ERa) expression was downregulated in the tamoxifen-induced hyperplasias. Reducing BRCA1 levels in MCF-7 cells using siRNA resulted in a relative increase in the agonist activity of tamoxifen. Results suggest a model of mammary cancer progression in which loss of full-length Brca1 altered the agonist/antagonist activity of tamoxifen, resulting in tamoxifen-induced mammary epithelial cell proliferation with subsequent loss of ERa expression and development of ERa-negative hyperplasias and adenocarcinomas.

show abstract

Section: Discussionsupporting

confidence: 91%

Promotion of mammary cancer development by tamoxifen in a mouse model of Brca1-mutation-related breast cancer

Jones

Halama

et al. 2005

Oncogene

View full text Add to dashboard Cite

show abstract

“…The tendency for a significant proportion of gene carriers (particularly BRCA1) to have oestrogen-receptor-negative breast cancer suggests limited efficacy of SERMS in the treatment of breast cancer in this group (Lakhani et al, 2002). There is limited evidence on the efficacy of mammography in pre-menopausal women, although some benefit is likely for those over age 40 (Lalloo et al, 1998;Moller et al, 2002). Lack of efficacy may be due to screening trials assessing younger age groups (i.e.…”

mentioning

confidence: 99%

Psychosocial impact of breast/ovarian (BRCA 1/2) cancer-predictive genetic testing in a UK multi-centre clinical cohort

et al. 2004

View full text Add to dashboard Cite

This multi-centre UK study assesses the impact of predictive testing for breast and ovarian cancer predisposition genes (BRCA1/2) in the clinical context. In the year following predictive testing, 261 adults (59 male) from nine UK genetics centres participated; 91 gene mutation carriers and 170 noncarriers. Self-report questionnaires were completed at baseline (pre-genetic testing) and 1, 4 and 12 months following the genetic test result. Men were assessed for general mental health (by general health questionnaire (GHQ)) and women for general mental health, cancer-related worry, intrusive and avoidant thoughts, perception of risk and risk management behaviour. Main comparisons were between female carriers and noncarriers on all measures and men and women for general mental health. Female noncarriers benefited psychologically, with significant reductions in cancer-related worry following testing (Po0.001). However, younger female carriers (o50 years) showed a rise in cancer-related worry 1 month post-testing (Po0.05). This returned to pre-testing baseline levels 12 months later, but worry remained significantly higher than noncarriers throughout (Po0.01). There were no significant differences in GHQ scores between males and females (both carriers and noncarriers) at any time point. Female carriers engaged in significantly more risk management strategies than noncarriers in the year following testing (e.g. mammograms; 92% carriers vs 30% noncarriers). In the 12 months post-testing, 28% carriers had bilateral risk-reducing mastectomy and 31% oophorectomy. Oophorectomy was confined to older (mean 41 yrs) women who already had children. However, worry about cancer was not assuaged by surgery following genetic testing, and this requires further investigation. In all, 20% of female carriers reported insurance problems. The data show persistent worry in younger female gene carriers and confirm changes in risk management consistent with carrier status. Men were not adversely affected by genetic testing in terms of their general mental health.

show abstract

“…This deletion was first described by Durocher et al (1996) in a patient diagnosed with breast cancer at 28 years and with ovarian cancer at 34 and with a strong family history (three breast cancers diagnosed at ages 26, 29 and 40 in different relatives). As this deletion was found in different ethnic groups like African Americans (Panguluri et al, 1999) and West Europeans (Moller et al, 2002), it is likely to be of ancient origin, although haplotype analysis might be required to confirm this hypothesis.…”

mentioning

confidence: 99%

BRCA1 mutations in Brazilian patients

et al. 2004

View full text Add to dashboard Cite

BRCA1 mutations are known to be responsible for the majority of hereditary breast and ovarian cancers in women with early onset and a family history of the disease. In this paper we present a mutational survey conducted in 47 Brazilian patients with breast/ovarian cancer, selected based on age at diagnosis, family history, tumor laterality, and presence of breast cancer in male patients. All 22 coding exons and intron-exon junctions were sequenced. Constitutional mutations were found in seven families, consisting of one insertion (insC5382) in exon 20 (four patients), one four base-pair deletion (3450-3453delCAAG) in exon 11 resulting in a premature stop codon (one patient), one transition (IVS17+2T > C) in intron 17 affecting a mRNA splicing site (one patient), and a C > T transition resulting in a stop-codon (Q1135X) in exon 11 (one patient). The identification of these mutations which are associated to hereditary breast and ovarian cancers will contribute to the characterization of the mutational spectrum of BRCA1 and to the improvement of genetic counseling for familial breast/ovarian cancer patients in Brazil. Key words: BRCA1, breast cancer, ovarian cancer. The Breast Cancer Linkage Consortium dataset indicates that the proportion of familial breast and ovarian cancers associated to BRCA1 or BRCA2 may be as high as 98% (Martin et al., 2001). Mutations in BRCA1 account for 45% of families with multiple cases of breast cancer and for at least 80% of families with early-onset breast and/or ovarian cancer (Miki et al., 1994). Moreover, 88% of families with at least four cases of early-onset breast cancer and one case of ovarian cancer are related to mutations in BRCA1 and BRCA2 (Unger et al., 2000). Furthermore, germ line BRCA1 or BRCA2 mutation carriers also have an increased risk of developing other cancers in prostate, stomach, colon, pancreas, fallopian tubes and uterus when compared to the general population (Offit, 1998;Brose et al., 2002). However, the alternative possibility of mutations in other, still unidentified susceptibility genes with low penetrance or chance clustering in families with multiple cases of breast/ovarian cancer without mutations in BRCA1 or BRCA2 remains to be determined.More than 800 different mutations were reported in BRCA1, and most of them are listed in the Breast Cancer Information Core (BIC -http://research.nhgri.nih.gov/bic/). Mutation carriers have an increased risk of developing breast cancer at different ages, with estimates of approximately 37% up to 40 years, 66% up to 55, 73% up to 70, and 82% over their entire lifetime (Hall et al., 1990;Brose et al., 2002). As for ovarian cancer, the risk was estimated to be 29% up to 50 years and 40% up to 70 years (Ford et al

show abstract

Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy

Cited by 102 publications

References 27 publications

Promotion of mammary cancer development by tamoxifen in a mouse model of Brca1-mutation-related breast cancer

Promotion of mammary cancer development by tamoxifen in a mouse model of Brca1-mutation-related breast cancer

Psychosocial impact of breast/ovarian (BRCA 1/2) cancer-predictive genetic testing in a UK multi-centre clinical cohort

BRCA1 mutations in Brazilian patients

Contact Info

Product

Resources

About