- Cancer Types
Information about risk, prevention, screening, symptoms, diagnosis, treatment, and support for all cancers Cancer A to Z - Cancer Treatment
Cancer Treatment
Information about cancer treatment, including surgery, chemotherapy, radiation therapy, clinical trials, proton therapy, complementary medicine, and cutting edge technologies.
- Risk and Prevention
- Cancer Drugs
- Support
Support
Ways for cancer patients and caregivers to cope with cancer, side effects, nutrition, general cancer support issues, grief/end of life issues, and shared survivor's experiences.
- Healthcare Professionals
- Clinical Trials
My Patient Treatment Binder
OncoLink Blogs
What's My Cancer Risk?
OncoPilot: Navigating Your Cancer Journey
Community Events Calendar
OncoLink eNews
Abramson Cancer CenterNCI CANCERLIT® Search: Breast Cancer, Hereditary - September 2002
National Cancer Institute®
Last Modified: September 1, 2002
- Measures of familial aggregation as predictors of breast-cancer risk.
- Intron 3 16 bp duplication polymorphism of p53 is associated with an increased risk for breast cancer by the age of 50 years.
- A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer.
- Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families.
- A breast cancer family from Spain with germline mutations in both the BRCA1 and BRCA2 genes.
- Minor role for BRCA2 (exon11) and p53 (exon 5-9) among Sudanese breast cancer patients.
- Two-stage designs for gene-disease association studies.
- Initiating oncogenic event determines gene-expression patterns of human breast cancer models.
- Analysis of 5382insC (BRCA1) and 6174delT (BRCA2) mutations in 382 healthy Chilean women with a family history of breast cancer.
- Concerns of women presenting to a comprehensive cancer centre for genetic cancer risk assessment.
- Management of women with a family history of breast cancer in the North West Region of England: training for implementing a vision of the
- Novel BRCA2 mutation in a Polish family with hamartoma and two male breast cancers.
- Sex hormone-binding globulin polymorphisms in familial and sporadic breast cancer.
- Male breast carcinoma.
- Allelic loss of chromosome 3p24 correlates with tumor progression rather than with retinoic acid receptor beta2 expression in breast carcinoma.
- Evaluation of two-dimensional differential gel electrophoresis for proteomic expression analysis of a model breast cancer cell system.
- Differences in breast cancer hormone receptor status and histology by race and ethnicity among women 50 years of age and older.
- [Gene expression profiling using cDNA arrays and prognosis of breast cancer]
- The genome's best friend.
- A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA
- Analysis of the complete sequence of the novel metastasis-associated candidate gene, mta1, differentially expressed in mammary adenocarcinoma
- Breast cancer metastasis-associated genes: role in tumour progression to the metastatic state.
- Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor.
- Loss of heterozygosity events impeding breast cancer metastasis contain the MTA1 gene.
- E-cadherin promoter methylation can regulate its expression in invasive ductal breast cancer tissue in Chinese woman.
- Artificial neural networks: a new model for assessing prognostic factors.
- P53 determination alongside classical prognostic factors in node-negative breast cancer: an evaluation at more than 10-year
- Identification of high risk breast-cancer patients by gene expression profiling.
- Ontario defies US firm's genetic patent, continues cancer screening.
- Breast cancer risk after childbirth in young women with family history (Denmark).
- [Reversal of nomegestrol acetate on multidrug resistance in drug-resistant human breast cancer cell line MCF7/ADR]
- Environmental toxins and breast cancer on Long Island. I. Polycyclic aromatic hydrocarbon DNA adducts.
- Differential effect of NAT2 on the association between active and passive smoke exposure and breast cancer risk.
- Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability.
- Heritable breast cancer in twins.
- Patients' attitudes about autonomy and confidentiality in genetic testing for breast-ovarian cancer susceptibility.
- [HER-2 diagnostics]
- Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing
- The ROSA26 LacZ-neo(R) insertion confers resistance to mammary tumors in Apc(Min/+) mice.
- Correlation of prostate-specific antigen promoter polymorphisms with clinicopathological characteristics in breast cancer.
- Molecular-cytogenetic analysis of fragmentation of chromosome 17 in the breast cancer cell line EFM-19.
- Differential modulation by estradiol of P-glycoprotein drug resistance protein expression in cultured MCF7 and T47D breast cancer cells.
- Correlation of MDR-1, nm23-H1 and H Sema E gene expression with histopathological findings and clinical outcome in ovarian and breast
- Ethnic variation in the HER-2 codon 655 genetic polymorphism previously associated with breast cancer.
- New human breast cancer cells to study progesterone receptor isoform ratio effects and ligand-independent gene regulation.
- In silico comparison of the transcriptome derived from purified normal breast cells and breast tumor cell lines reveals candidate upregulated
- Characterization of 2 novel and 2 recurring BRCA1 germline mutations in breast and/or ovarian carcinoma patients from the area of Naples.
- Possible co-regulation of genes associated with enhanced progression of mammary adenocarcinomas.
- DNA aneuploidy in relation to the combination of analysis of estrogen receptor, progesterone receptor, p53 protein and epidermal growth factor
- Regulation of major histocompatibility complex class I expression by NF-kappaB-related proteins in breast cancer cells.
- Frequent loss of heterozygosity at the DNA mismatch-repair loci hMLH1 and hMSH3 in sporadic breast cancer.
- The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2).
- Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor and parthenolide.
- Copper-transporting P-type adenosine triphosphatase (ATP7B) is expressed in human breast carcinoma.
- Estrogen receptor-beta expression in hereditary breast cancer.
- Molecular and biologic markers of premalignant lesions of human breast.
- The effect of DNA-alkylating agents on gene expression from two integrated reporter genes in a mouse mammary tumor line.
- Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators.
- Frequent mutations of the Trp53, Hras1 and beta-catenin (Catnb) genes in 1,3-butadiene-induced mammary adenocarcinomas in B6C3F1 mice.
- Absence of major defects in non-homologous DNA end joining in human breast cancer cell lines.
- BRCA2 and Smad3 synergize in regulation of gene transcription.
- Molecular and genetic abnormalities in radial scar.
- Tamoxifen enhances interferon-regulated gene expression in breast cancer cells.
- Assessing the significance of consistently mis-regulated genes in cancer associated gene expression matrices.
- The HER2 extracellular domain as a prognostic and predictive factor in breast cancer.
- Reliability of the tissue microarray based FISH for evaluation of the HER-2 oncogene in breast carcinoma.
- Mutational analysis of the class I beta-tubulin gene in human breast cancer.
- TP53 mutations in breast cancer tumors of patients from Rio de Janeiro, Brazil: association with risk factors and tumor characteristics.
- Functional allelic loss detected at the protein level in archival human tumours using allele-specific E-cadherin monoclonal antibodies.
- Family history of cancer and incidence of acute leukemia in adults.
- Genetic and environmental determinants on tissue response to in vitro carcinogen exposure and risk of breast cancer.
- CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3.
- Heritability of mammographic density, a risk factor for breast cancer.
- Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women.
- Analysis of estrogen receptor polymorphism in codon 325 by PCR-SSCP in breast cancer: association with lymph node metastasis.
- Male breast cancer: a marker for secondary and familial neoplasms.
- Multiparametric flow cytometric analysis in a breast cancer cell line (MCF-7).
- Clinical geneticists' attitudes and practice towards testing for breast cancer susceptibility genes.
- Breast cancer susceptibility-A new look at an old model.
- Inducible expression of FGF-3 in mouse mammary gland.
- ATM heterozygosity and cancer risk.
- Pathway pathology: histological differences between ErbB/Ras and Wnt pathway transgenic mammary tumors.
- Correlation of DNA hypomethylation at pericentromeric heterochromatin regions of chromosomes 16 and 1 with histological features and
- Breast cancer after mantle irradiation for Hodgkin's disease: correlation of clinical, pathologic, and molecular features including
- MAGE-A gene expression pattern in primary breast cancer.
- The p53 pathway in breast cancer.
- BRCA1 induces DNA damage recognition factors and enhances nucleotide excision repair.
- Inactivation of Apc perturbs mammary development, but only directly results in acanthoma in the context of Tcf-1 deficiency.
- [Temporary dependency of steroid-receptor prognostic value in breast cancer]
- Analysis of BRCA1 and BRCA2 in breast and breast/ovarian cancer families shows population substructure in the Iberian peninsula.
- Multivariate analysis of bcl-2, apoptosis, P53 and HER-2/neu in breast cancer: a short-term follow-up.
- Familial risk factors for breast cancer among Arab women in Israel.
- CCND1- and ERBB2-gene deregulation and PTEN mutation analyses in invasive lobular carcinoma of the breast.
Table of Contents
1
UI - 11822727
AU - Boucher KM; Kerber RA
TI -
Measures of familial aggregation as predictors of breast-cancer risk.
SO - J Epidemiol Biostat 2001;6(5):377-85
AD - Huntsman Cancer Institute and Department of Oncological Sciences,
University of Utah, Salt Lake City 84112, USA.
BACKGROUND: Several measures of familial disease aggregation have been
proposed, but only a few of these are designed to be implemented at the
individual level. We evaluate two of them in the context of
breast-cancer incidence. METHODS: A population-based cohort consisting
of 114 429 women born between 1874 and 1931 and at risk for breast
cancer after 1965 was identified by linking the Utah Population Data
Base and the Utah Cancer Registry. Two competing methods were used to
obtain predictors of familial aggregation of risk: the number of
first-degree relatives with breast cancer (NIST) and the familial
standardised incidence ratio (FSIR), which weights the disease status of
relatives based on their degree of relatedness with the proband.
Relative risks were estimated using Mantel-Haenszel. Poisson regression
and spline regression methods. The age-dependent hazard function was
also estimated. RESULTS: Compared to a baseline category containing
91.5% of the subjects, the 0.7% of subjects identified as high risk
using the FSIR criterion had a relative risk of about 2.8, while those
identified as high risk using the NIST criterion had a relative risk of
2.0. Moderate-risk subjects had a relative risk of about 1.75 using
either criterion. FSIR was a significant predictor of risk even for
those with no affected first-degree relatives. No decline in the
baseline risk was observed at advanced ages. CONCLUSIONS: FSIR appears
to be a better predictor of breast-cancer risk than NIST, particularly
for high-risk subjects.
2
UI - 11927843
AU - Wang-Gohrke S; Becher H; Kreienberg R; Runnebaum IB; Chang-Claude J
TI -
Intron 3 16 bp duplication polymorphism of p53 is associated with an
increased risk for breast cancer by the age of 50 years.
SO - Pharmacogenetics 2002 Apr;12(3):269-72
AD - Department of Obstetrics and Gynaecology, Molecular Biology Laboratory,
University of Ulm, Germany.
We used a large population-based case-control study to determine whether
three known p53 polymorphisms, intron 3 16 bp duplication, codon
72(Arg/Pro) and intron 6 MspI restriction fragment length polymorphism,
alter the risk for breast cancer in German women. For all three
polymorphisms, the odds ratios (ORs) for breast cancer were increased in
women carrying the rare allele; however, this was statistically
significant only for the 16 bp duplication polymorphism. Compared with
the 16 bp duplication wild-type A1/A1 genotype, ORs for A1/A2 genotype
and A2/A2 genotype were 1.3 [95% confidence interval (CI) 1.0-1.7] and
1.7 (95% CI 0.8-3.4), suggesting an allele dosage effect (trend test, P
= 0.03). Significant evidence was found for a differential effect by
family history of breast cancer (P = 0.03 for interaction), with the OR
being 5.3 among women with a first degree family history. Our data
suggest that inheritance of an intronic polymorphism in the p53 gene
increases breast cancer risk appreciably in women by the age of 50 years
with a family history of breast cancer in the German population.
3
UI - 12161606
AU - Chappuis PO; Goffin J; Wong N; Perret C; Ghadirian P; Tonin PN; Foulkes
TI -
WD
A significant response to neoadjuvant chemotherapy in BRCA1/2 related
breast cancer.
SO - J Med Genet 2002 Aug;39(8):608-10
4
UI - 12161607
AU - Kauff ND; Perez-Segura P; Robson ME; Scheuer L; Siegel B; Schluger A;
TI -
Rapaport B; Frank TS; Nafa K; Ellis NA; Parmigiani G; Offit K
Incidence of non-founder BRCA1 and BRCA2 mutations in high risk
Ashkenazi breast and ovarian cancer families.
SO - J Med Genet 2002 Aug;39(8):611-4
5
UI - 12161611
AU - Caldes T; de la Hoya M; Tosar A; Sulleiro S; Godino J; Ibanez D; Martin
TI -
M; Perez-Segura P; Diaz-Rubio E
A breast cancer family from Spain with germline mutations in both the
BRCA1 and BRCA2 genes.
SO - J Med Genet 2002 Aug;39(8):e44
6
UI - 11883440
AU - Masri MA; Abdel Seed NM; Fahal AH; Romano M; Baralle F; El Hassam AM;
TI -
Ibrahim ME
Minor role for BRCA2 (exon11) and p53 (exon 5-9) among Sudanese breast
cancer patients.
SO - Breast Cancer Res Treat 2002 Jan;71(2):145-7
AD - Institute of Endemic Diseases, University of Khartoum, Sudan.
A cohort of 20 breast cancer patients from the Sudan was tested for germ
line and somatic mutation in their BRCA2 exon 11 as well as the main
conserved area of the p53 tumor suppressor gene. The results indicate
that both regions may play a limited role in the pathogenesis of breast
cancer in those patients. The fact that there are no somatic mutations
detected in p53 was particularly surprising as the expected rate for
mutations in breast cancer is 30-50%.
7
UI - 11890312
AU - Satagopan JM; Verbel DA; Venkatraman ES; Offit KE; Begg CB
TI -
Two-stage designs for gene-disease association studies.
SO - Biometrics 2002 Mar;58(1):163-70
AD - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering
Cancer Center, New York, New York 10021, USA. satago@biosta.mskcc.org
The goal of this article is to describe a two-stage design that
maximizes the power to detect gene-disease associations when the
principal design constraint is the total cost, represented by the total
number of gene evaluations rather than the total number of individuals.
In the first stage, all genes of interest are evaluated on a subset of
individuals. The most promising genes are then evaluated on additional
subjects in the second stage. This will eliminate wastage of resources
on genes unlikely to be associated with disease based on the results of
the first stage. We consider the case where the genes are correlated and
the case where the genes are independent. Using simulation results, it
is shown that, as a general guideline when the genes are independent or
when the correlation is small, utilizing 75% of the resources in stage 1
to screen all the markers and evaluating the most promising 10% of the
markers with the remaining resources provides near-optimal power for a
broad range of parametric configurations. This translates to screening
all the markers on approximately one quarter of the required sample size
in stage 1.
8
UI - 12011455
AU - Desai KV; Xiao N; Wang W; Gangi L; Greene J; Powell JI; Dickson R; Furth
TI -
P; Hunter K; Kucherlapati R; Simon R; Liu ET; Green JE
Initiating oncogenic event determines gene-expression patterns of human
breast cancer models.
SO - Proc Natl Acad Sci U S A 2002 May 14;99(10):6967-72
AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer
Institute, Bethesda, MD 20892, USA.
Molecular expression profiling of tumors initiated by transgenic
overexpression of c-myc, c-neu, c-ha-ras, polyoma middle T antigen
(PyMT) or simian virus 40 T/t antigen (T-ag) targeted to the mouse
mammary gland have identified both common and oncogene-specific events
associated with tumor formation and progression. The tumors shared great
similarities in their gene-expression profiles as compared with the
normal mammary gland with an induction of cell-cycle regulators,
metabolic regulators, zinc finger proteins, and protein tyrosine
phosphatases, along with the suppression of some protein tyrosine
kinases. Selection and hierarchical clustering of the most variant
genes, however, resulted in separating the mouse models into three
groups with distinct oncogene-specific patterns of gene expression. Such
an identification of targets specified by particular oncogenes may
facilitate development of lesion-specific therapeutics and preclinical
testing. Moreover, similarities in gene expression between human breast
cancers and the mouse models have been identified, thus providing an
important component for the validation of transgenic mammary cancer
models.
9
UI - 12125210
AU - Jara L; Ampuero S; Seccia L; Bustamante M; Blanco R; Ojeda JM
TI -
Analysis of 5382insC (BRCA1) and 6174delT (BRCA2) mutations in 382
healthy Chilean women with a family history of breast cancer.
SO - Biol Res 2002;35(1):85-93
AD - Human Genetics Program, Institute of Biomedical Sciences, School of
Medicine, University of Chile. ljara@machi.med.uchile.cl
Breast cancer is the most common malignancy among women. Chilean studies
reveal that this cancer presents the third highest mortality rate. A
family history of breast cancer is one of the major risk factors for the
development of this disease. BRCA1 and BRCA2 are the two main hereditary
breast cancer susceptibility genes, and mutations in these genes are
related to inherited breast cancer. In specific populations only some
mutations have been found to be associated with susceptibility. The
purpose of this study was to establish the frequency of 5382insC (BRCA1)
and 6174delT (BRCA2) germline mutations in 382 healthy Chilean women
with at least two relatives affected with breast cancer and in probands
and their relatives from 8 high risk families for breast cancer, using
mismatch PCR assay. The results obtained showed that 5382insC and
6174delT mutations were not found in either of the groups studied. The
ethnic origin of the contemporary Chilean population and the data
reported in the literature suggest that these mutations may be absent or
have a very low frequency in this population.. This genetic study is
part of a breast cancer screening program that also includes annual
mammography and clinical breast examination over a five-year period.
Strategies to reduce morbidity and mortality associated with breast
cancer lie in early detection in women with genetic risk.
10
UI - 12114489
AU - MacDonald DJ; Choi J; Ferrell B; Sand S; McCaffrey S; Blazer KR; Grant
TI -
M; Weitzel JN
Concerns of women presenting to a comprehensive cancer centre for
genetic cancer risk assessment.
SO - J Med Genet 2002 Jul;39(7):526-30
11
UI - 12114490
AU - McAllister M; O'Malley K; Hopwood P; Kerr B; Howell A; Evans DG
TI -
Management of women with a family history of breast cancer in the North
West Region of England: training for implementing a vision of the
future.
SO - J Med Genet 2002 Jul;39(7):531-5
12
UI - 12114492
AU - Kwiatkowska E; Brozek I; Izycka-Swieszewska E; Limon J; Mackiewicz A
TI -
Novel BRCA2 mutation in a Polish family with hamartoma and two male
breast cancers.
SO - J Med Genet 2002 Jul;39(7):E35
13
UI - 12151349
AU - Forsti A; Jin Q; Grzybowska E; Soderberg M; Zientek H; Sieminska M;
TI -
Rogozinska-Szczepka J; Chmielik E; Utracka-Hutka B; Hemminki K
Sex hormone-binding globulin polymorphisms in familial and sporadic
breast cancer.
SO - Carcinogenesis 2002 Aug;23(8):1315-20
AD - Department of Biosciences at Novum, Karolinska Institute, SE-14157
Huddinge, Sweden. asta.forsti@cnt.ki.se
Ovarian steroids are one of the strongest risk factors for breast
cancer. Sex hormone-binding globulin (SHBG) binds and transports sex
steroids in the blood, regulating their bioavailable fraction and access
to target cells. It can also inhibit the estradiol-induced proliferation
of breast cancer cells through its membrane receptor. Three
coding-region polymorphisms, which lead to an amino acid change, have
been reported. We studied the influence of these three polymorphisms on
breast cancer risk in three different populations: Polish familial
breast cancer cases, 27% of them carrying a BRCA1/BRCA2 mutation, Nordic
familial and sporadic breast cancer cases. The reported G to A
polymorphism in exon 1 was not found in the 423 analyzed samples.
Instead, we found a C to T transition causing an arg to cys amino acid
change within the same codon in one Polish breast cancer patient and her
daughter. Both of them were heterozygotes for the exon 8 G to A
polymorphism as well. They were diagnosed for bilateral breast cancer
and carried a BRCA1 mutation (5382insC). Analysis of the tumor samples
showed that they had lost the wild-type allele both at exons 1 and 8 of
the SHBG gene. Analysis of the other Polish samples showed no
correlation of the exon 8 polymorphism to breast cancer, bilateral
breast cancer, BRCA1/BRCA2 mutations or age at diagnosis. No association
of the exon 8 polymorphism with breast cancer in the Nordic familial or
sporadic cases was found. The C to T polymorphism located in exon 4 was
rare in all the studied populations (overall allele frequency 0.011).
However, in each of the study populations there was a trend for a lower
variant allele frequency in cancer cases than in controls. Variant
allele frequency in all the breast cancer cases was significantly lower
than in all the controls (chi(2) = 5.27, P-value 0.02; odds ratio =
0.23, 95% confidence interval 0.05-0.84).
14
UI - 12174988
AU - Meguerditchian AN; Falardeau M; Martin G
TI -
Male breast carcinoma.
SO - Can J Surg 2002 Aug;45(4):296-302
AD - Department of Surgery, Universite Laval, Quebec City, Que.
OBJECTIVE: To review the epidemiology, presentation, diagnosis,
molecular genetics, treatment and prognosis of male breast cancer. DATA
SOURCES: Articles, written in English or French, selected from the
"male breast cancer," according to the following criteria: covering
institutional experience or comparing diagnostic and treatment
modalities, and epidemiologic or general reviews. STUDY SELECTION: Of
198 articles found 50 fulfilled the review criteria. DATA SYNTHESIS:
Risk factors included advanced age, a positive family history, Jewish
origin, black race, excess exposure to female hormones (Klinefelter's
syndrome), environmental exposure (irradiation), alcohol, obesity,
higher socioeconomic or higher educational status and childlessness.
Gynecomastia remains a controversial factor, this term being used for
both a histologic reality and a physical finding. Advanced disease is
characterized by pain, bloody discharge and skin ulceration. There is no
definitive diagnostic algorithm. Experience with male breast mammography
is limited, and imaging is less informative for patients under 50 years
of age. Fine-needle aspiration tends to overestimate the rate of
malignancy. The commonest histologic finding is infiltrating ductal
adenocarcinoma. Treatment includes modified radical mastectomy, followed
by cyclophosphamide-methotrexate-5-fluorouracil or
5-fluorouracil-Adriamycin-cyclophosphamide chemotherapy for disease of
stage II or greater. Radiotherapy does not seem to add any benefit. The
disease is highly receptor-positive; however, many patients discontinue
tamoxifen due to side effects. The most important prognostic factors are
tumour size, lymphatic invasion and axillary node status. CONCLUSIONS:
Because of the low incidence of male breast cancer, advances will be
obtained mainly with the rapid transfer of newly gained knowledge in
female mammary neoplasia. The increased use of adjuvant chemotherapy
combined with tamoxifen postoperatively may have a positive impact on
survival. Public education should be oriented toward men at higher risk
to reduce the interval between appearance of symptoms and consultation.
Rigorous data collection will allow for thorough reporting of risk
factors and thus the possibility of characterizing the etiology of this
disease.
15
UI - 11767003
AU - Yang Q; Yoshimura G; Nakamura M; Nakamura Y; Shan L; Suzuma T; Tamaki T;
TI -
Umemura T; Mori I; Kakudo K
Allelic loss of chromosome 3p24 correlates with tumor progression rather
than with retinoic acid receptor beta2 expression in breast carcinoma.
SO - Breast Cancer Res Treat 2001 Nov;70(1):39-45
AD - Department of Surgery, Kihoku Hospital, Wakayama Medical University
School of Medicine, Wakayama City, Japan.
yang-qf@mail.wakayama-med.ac.jp
A tumor suppressor gene. retinoic acid receptor (RAR) beta2, has been
mapped to chromosome 3p24, a region where loss of heterozygosity (LOH)
has been observed commonly in carcinomas of various tumor tissues. RAR
beta2 expression is reduced or lost in many malignant tumors including
breast cancer, however, whether LOH accounts for the loss of expression
of RAR beta2 in breast cancer is unknown. We, therefore, assessed LOH on
chromosome band 3p24 to correlate it with RAR beta2 expression and other
established prognostic parameters in 52 breast carcinomas. Based on
three microsatellites, D3S 1283, D3S 1293 and D3S 1286. all of the
tumors were informative, of these, 12 (23%) exhibited LOH. RAR beta2
expression was lost in 42% (19/45) of these samples. We found that LOH
on chromosome band 3p24 was not correlated with loss of RAR beta2, but
correlated with higher histological grade, p53-positivity, and loss of
estrogen and progesterone receptors. Our findings suggest that LOH of
the RAR beta2 gene does not account for the frequent loss of RAR beta2
expression in breast cancer but the genomic structural alteration at or
close to the RAR beta2 gene locus are likely to be associated with tumor
progression and/or loss of hormonal dependency.
16
UI - 12096126
AU - Gharbi S; Gaffney P; Yang A; Zvelebil MJ; Cramer R; Waterfield MD; Timms
TI -
JF
Evaluation of two-dimensional differential gel electrophoresis for
proteomic expression analysis of a model breast cancer cell system.
SO - Mol Cell Proteomics 2002 Feb;1(2):91-8
AD - Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W
7BS, United Kingdom.
The technique of fluorescent two-dimensional (2D) difference gel
electrophoresis for differential protein expression analysis has been
evaluated using a model breast cancer cell system of ErbB-2
overexpression. Labeling of paired cell lysate samples with N-hydroxy
succinimidyl ester-derivatives of fluorescent Cy3 and Cy5 dyes for
separation on the same 2D gel enabled quantitative, sensitive, and
reproducible differential expression analysis of the cell lines.
SyproRuby staining was shown to be a highly sensitive and 2D difference
gel electrophoresis-compatible method for post-electrophoretic
visualization of proteins, which could then be picked and identified by
matrix-assisted laser-desorption ionization mass spectroscopy. Indeed,
from these experiments, we have identified multiple proteins that are
likely to be involved in ErbB-2-mediated transformation. A triple dye
labeling methodology was used to identify proteins differentially
expressed in the cell system over a time course of growth factor
stimulation. A Cy2-labeled pool of samples was used as a standard with
all Cy3- and Cy5-labeled sample pairs to facilitate cross-gel
quantitative analysis. DeCyder (Amersham Biosciences, Inc.) software was
used to distinguish clear statistical differences in protein expression
over time and between the cell lines.
17
UI - 12101106
AU - Li CI; Malone KE; Daling JR
TI -
Differences in breast cancer hormone receptor status and histology by
race and ethnicity among women 50 years of age and older.
SO - Cancer Epidemiol Biomarkers Prev 2002 Jul;11(7):601-7
AD - Fred Hutchinson Cancer Research Center, Division of Public Health
Sciences, Seattle, Washington 98109-1024, USA. cili@fhcrc.org
Numerous studies have demonstrated differences in certain biological
breast cancer characteristics associated with survival, including
hormone receptor status and histology, among women of different racial
and ethnic groups. However, women classified as "Asian or Pacific
Islanders" or "Hispanic whites" represent heterogeneous populations, and
few studies have separately evaluated subgroups of these populations
with respect to these breast tumor characteristics. Using data obtained
from 11 cancer registries that participate in the Surveillance,
Epidemiology, and End Results (SEER) Program, the tumor characteristics
of 93,317 women in whom invasive breast cancer was diagnosed from 1992
to 1998 were compared by race and ethnicity using unconditional and
polytomous logistic regression. The study consisted of 75,978
non-Hispanic whites, 6,915 African Americans, 203 Native Americans,
5,750 Asians/Pacific Islanders, and 4,471 Hispanic whites. Eight
Asian/Pacific Islander and four Hispanic white subgroups were also
analyzed separately. Relative to non-Hispanic whites, African Americans,
Native Americans, Filipinos, Chinese, Koreans, Vietnamese,
Indians/Pakistanis, Mexicans, South/Central Americans, and Puerto Ricans
living in the United States had 1.4- to 3.1-fold elevated risks of
presenting with estrogen receptor-negative/progesterone
receptor-negative breast cancer. Numerous differences by histological
type, including lobular, ductal/lobular, mucinous, comedocarcinoma,
tubular, and medullary histologies, were also observed by
race/ethnicity. Breast cancer tumor characteristics differ by
race/ethnicity in the United States. Both biological and lifestyle
factors likely contribute to these findings. Our results may explain, to
some extent, the differences in breast cancer stage and survival
observed by race/ethnicity. Understanding the factors underlying these
differences may provide further insight into breast cancer etiology in
different populations.
18
UI - 12135856
AU - Bertucci F; Nasser V; Houlgatte R; Birnbaum D
TI -
[Gene expression profiling using cDNA arrays and prognosis of breast
cancer]
SO - Bull Cancer 2002 Jun;89(6):571-4
AD - Departement d'oncologie moleculaire (TAGC: technologies avancees pour le
genome et la clinique), Institut Paoli-Calmettes, IFR57, 27, bd Le
-Roure, 13009 Marseille, France.
Breast cancer is a major health problem. Clinical heterogeneity makes
prognosis and sensitivity to treatment highly variable among patients.
The recently developed cDNA array technology allows to analyse the
expression of thousands of genes simultaneously. Results of the
pioneering studies are promising: expression profiling of breast tumours
using cDNA arrays seems able to identify new prognostic sub-classes
unidentifiable using conventional parameters.
19
UI - 12101401
AU - Jinks-Robertson S
TI -
The genome's best friend.
SO - Nat Genet 2002 Aug;31(4):331-2
20
UI - 8083195
AU - Toh Y; Pencil SD; Nicolson GL
TI -
A novel candidate metastasis-associated gene, mta1, differentially
expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA
cloning, expression, and protein analyses.
SO - J Biol Chem 1994 Sep 16;269(37):22958-63
AD - Department of Tumor Biology, University of Texas M. D. Anderson Cancer
Center, Houston 77030.
To understand the genes involved in breast cancer invasion and
metastasis, we analyzed a novel candidate metastasis-associated gene,
mta1, which was isolated by differential cDNA library screening using
the 13762NF rat mammary adenocarcinoma metastatic system. Northern blot
analyses showed that the mRNA expression level of the mta1 gene was
4-fold higher in the highly metastatic cell line MTLn3 than in the
nonmetastatic cell line MTC.4. The mta1 gene was expressed in various
normal rat organs, especially in the testis, suggesting its essential
normal function. The mRNA expression levels of the human homologue of
this gene also correlated with the metastatic potential in two human
breast cancer metastatic systems. The full-length mta1 cDNA sequence
contained an open reading frame encoding a protein of 703 amino acid
residues, and sequence analysis by data base homology search indicated
that mta1 is a novel gene. The Mta1 protein contained several possible
phosphorylation sites, and a proline-rich amino acid stretch at the
carboxyl-terminal end completely matched the consensus sequence for the
src homology 3 domain-binding motif. Using antibodies raised against
glutathione S-transferase-Mta1 fusion protein or a synthetic
oligopeptide, Western blots showed that the molecular mass of the Mta1
protein was approximately 80 kDa, and the levels of the Mta1 protein
also correlated with the metastatic potential, results similar to those
obtained from the Northern analyses. Thus, the novel gene mta1 may
encode a molecule that is functional in normal cells as well as in
breast cancer invasion and metastasis.
21
UI - 7607577
AU - Toh Y; Pencil SD; Nicolson GL
TI -
Analysis of the complete sequence of the novel metastasis-associated
candidate gene, mta1, differentially expressed in mammary adenocarcinoma
and breast cancer cell lines.
SO - Gene 1995 Jun 14;159(1):97-104
AD - Department of Tumor Biology, University of Texas M.D. Anderson Cancer
Center, Houston 77030, USA.
To understand the genes and gene products involved in breast cancer
invasion and metastasis, we previously isolated ten differentially
expressed genes by differential cDNA library screening techniques, using
the 13762NF rat mammary adenocarcinoma metastatic system. In this study,
we further analysed a novel candidate metastasis-associated gene, mta1,
previously designated clone 10.14. Northern blotting analyses showed
that the steady-state mRNA expression level of mta1 was fourfold higher
in a highly metastatic line (MTLn3) than in a nonmetastatic line
(MTC.4). The mta1 gene was expressed at low levels in various normal rat
organs, except testis, where it was expressed in high amounts. The mRNA
expression levels of the human homologue of this gene were also examined
in two human breast cancer metastatic systems; the ratios of mRNA were
estimated to be MCF-7 (nonmetastatic):MCF7/LCC1 (invasive):MCF7/LCC2
(metastatic) = 1:2:4 and MDA-MB-468 (nonmetastatic):MDA231 (metastatic)
= 1:4. Thus, the expression of this gene directly correlated with
metastatic potential in two human systems, as well as in the rat
metastatic system. Clone 10.14 was used to isolate a full-length cDNA
clone for mta1, yielding the clone p10.14-C4.5, which was sequenced and
analysed. Clone p10.14-C4.5 was 2756-bp long and contained a single open
reading frame that could encode a protein of 703 amino acid (aa)
residues. The aa sequence of mta1 was found to be novel by database
homology search and contained possible phosphorylation sites for
tyrosine kinase, protein kinase C and casein kinase II. A Pro-rich
stretch was found at the C-terminal end that completely matched the
consensus sequence for the SH3-binding motif.(ABSTRACT TRUNCATED AT 250
WORDS)
22
UI - 9513727
AU - Nicolson GL
TI -
Breast cancer metastasis-associated genes: role in tumour progression to
the metastatic state.
SO - Biochem Soc Symp 1998;63():231-43
AD - Institute for Molecular Medicine, Irvine, CA 92614, USA.
Breast cancer patients usually do not die of their primary cancers; they
die of metastatic disease. Thus understanding the progression of breast
cancer to the metastatic state and the changes that take place in highly
malignant breast cells are important goals that could eventually result
in new therapeutic approaches to highly progressive breast disease.
Changes in the expression of certain genes or alterations in gene
structures and encoded products can result in benign tumour cells
progressing to the metastatic state. Experimentally, this has been
performed by transferring dominantly acting oncogenes into susceptible
cells and then testing the malignant properties of these cells in
suitable animal models, but such rapid qualitative changes occur in vivo
only rarely, and the natural progression of mammary cells to the
metastatic state is thought to occur through a slow stepwise process
that can take several years. Some of the slow stepwise changes in
mammary cancer progression can be reversible and need not involve
dominantly acting oncogenes or tumour suppressor genes, consistent with
clinical observations. An important element of the natural progression
of mammary tumours to malignancy may be their ability to circumvent
microenvironmental controls that regulate growth and cellular diversity,
a process that appears to involve mainly quantitative changes in gene
expression, resulting in loss of normal cellular regulation. One of the
important mechanisms of cellular regulation in epithelial tissues, such
as those found in the breast, is mediated by intercellular junctional
communication. Alterations in gene expression can result in loss of
gap-junctional communication, concomitant with cellular diversification
and progression. It is thought that the highly malignant cancer cells
that have slowly evolved in vivo with only a few qualitative changes in
gene structure have undergone extensive cycles of diversification and
the accumulation of several quantitative changes in the expression of
various genes that encode products related to malignancy. We have
identified some of the genes that are related to progression and
metastasis in breast cancer. For example, one of these genes, a novel
gene called mta1 (in rodents) or MTA1 (in humans) appears to be involved
in mammary cell motility and growth regulation. Thus highly malignant
cellular phenotypes can arise rapidly due to specific qualitative
changes in critical controlling genes, or more slowly via less critical
qualitative genetic changes coupled with other cellular changes, such as
loss of intercellular communication, and changes in gene expression,
such as in the MTA1 gene, resulting in cellular diversification and
ultimately tumour progression to the metastatic state.
23
UI - 11146623
AU - Mazumdar A; Wang RA; Mishra SK; Adam L; Bagheri-Yarmand R; Mandal M;
TI -
Vadlamudi RK; Kumar R
Transcriptional repression of oestrogen receptor by
metastasis-associated protein 1 corepressor.
SO - Nat Cell Biol 2001 Jan;3(1):30-7
AD - Department of Molecular and Cellular Oncology, University of Texas M. D.
Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030,
USA.
Activation of the heregulin/HER2 pathway in oestrogen receptor
(ER)-positive breast-cancer cells leads to suppression of
oestrogen-receptor element (ERE)-driven transcription and disruption of
oestradiol responsiveness, and thus contributes to progression of
tumours to more invasive phenotypes. Here we report the identification
of metastatic-associated protein 1 (MTA1), a component of histone
deacetylase (HDAC) and nucleosome-remodelling complexes, as a gene
product induced by heregulin-beta1 (HRG). Stimulation of cells with HRG
is accompanied by suppression of histone acetylation and enhancement of
deacetylase activity. MTA1 is also a potent corepressor of ERE
transcription, as it blocks the ability of oestradiol to stimulate
ER-mediated transcription. The histone-deacetylase inhibitor
trichostatin A blocks MTA1-mediated repression of ERE transcription.
Furthermore, MTA1 directly interacts with histone deacetylase-1 and -2
and with the activation domain of ER-alpha. Overexpression of MTA1 in
breast-cancer cells is accompanied by enhancement of the ability of
cells to invade and to grow in an anchorage-independent manner. HRG also
promotes interaction of MTA1 with endogenous ER and association of MTA1
or HDAC with ERE-responsive target-gene promoters in vivo. These results
identify ER-mediated transcription as a nuclear target of MTA1 and
indicate that HDAC complexes associated with the MTA1 corepressor may
mediate ER transcriptional repression by HRG.
24
UI - 11325822
AU - Martin MD; Fischbach K; Osborne CK; Mohsin SK; Allred DC; O'Connell P
TI -
Loss of heterozygosity events impeding breast cancer metastasis contain
the MTA1 gene.
SO - Cancer Res 2001 May 1;61(9):3578-80
AD - Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Breast cancer mortality is seldom attributable to the primary tumor, but
rather to the presence of systemic (metastatic) disease. Axillary lymph
node dissection can identify the presence of metastatic breast cancer
cells and serves as a marker for systemic disease. Previous work in our
laboratory determined that rates of loss of heterozygosity (LOH) of a
1.6-Mb region of chromosome 14q 31.2 is much higher in axillary lymph
node-negative primary breast tumors than in axillary lymph node-positive
primary breast tumors (P. O'Connell et al., J. NATL: Cancer INST:, 91:
1391-1397, 1999.). This unusual observation suggests that, whereas the
LOH of this region promotes primary breast cancer formation, some
gene(s) mapping to this 1.6-Mb region is rate-limiting for breast cancer
metastasis. Thus, if primary breast cancers delete this region, their
ability to metastasize decreases. To identify this gene(s), we have
physically mapped this area of chromosome 14q, confirmed the position of
two known genes and 13 other expressed sequence tags into this 1.6-Mb
region. One of these, the metastasis-associated 1 (MTA1) gene,
previously identified as a metastasis-promoting gene (Y. Toh et al., J.
BIOL: CHEM:, 269: 22958-22963, 1994.), mapped to the center of our
1.6-Mb target region. Thus, MTA1 represents a strong candidate for this
breast cancer metastasis-promoting gene.
25
UI - 12127160
AU - Hu XC; Loo WT; Chow LW
TI -
E-cadherin promoter methylation can regulate its expression in invasive
ductal breast cancer tissue in Chinese woman.
SO - Life Sci 2002 Aug 9;71(12):1397-404
AD - Department of Surgery, University of Hong Kong Medical Center, Queen
Mary Hospital, Pokfulam, Hong Kong, China.
Promoter methylation is an important mechanism of regulating E-cadherin
expression. Methylation-specific PCR (MSP) assay was done to evaluate
the promoter methylation status of E-cadherin gene in primary tumor
samples from 23 cases of Chinese women with invasive ductal breast
cancers. Western blotting assay was employed for E-cadherin and
beta-actin expressions. Positive MSP results occurred in 26.1% (6/23) of
primary tumor samples and none of four normal skin samples. These
molecular events tended to occur in breast cancers associated with poor
prognosis. Whereas the mean ratio of CDH1/beta-actin for six
MSP-positive cases was 0.0290 +/- 0.0355, the mean ratio for 17
MSP-negative cases was 0.4726 +/- 0.5049 (P = 0.046). In conclusion,
aberrant E-cadherin methylation preferentially occurs in invasive ductal
breast cancer associated with poor prognosis and is one of the
mechanisms of E-cadherin expression silence in breast cancers from
Chinese women.
26
UI - 10847454
AU - Grumett SA; Snow PB
TI -
Artificial neural networks: a new model for assessing prognostic
factors.
SO - Ann Oncol 2000 Apr;11(4):383-4
27
UI - 10847456
AU - Ferrero JM; Ramaioli A; Formento JL; Francoual M; Etienne MC; Peyrottes
TI -
I; Ettore F; Leblanc-Talent P; Namer M; Milano G
P53 determination alongside classical prognostic factors in
node-negative breast cancer: an evaluation at more than 10-year
follow-up.
SO - Ann Oncol 2000 Apr;11(4):393-7
AD - The Centre Antoine Lacassagne, Nice, France.
BACKGROUND: There is heterogeneity of methods and conflicting results
concerning the prognostic value of p53 in node-negative breast cancer.
The clinical value of a quantitative method for measuring tumoralp53
content still needs to be evaluated. PATIENTS AND METHODS: A long-term
retrospective study was conducted on 297 node-negative patients with a
median follow-up greater than 10 years (11 years, 101-172 months).
Classic prognostic factors were considered including age, tumor size,
histoprognostic grade and estradiol (ER) and progesterone receptors
(PR). In addition, the value of p53 determination (immunoluminometric
assay in tumor cytosol) was assessed for this long follow-up period.
RESULTS: p53 concentrations were significantly linked to the
histological grade (P = 0.001), to tumor size (P = 0.02) and ER status
(P = 0.01). Higher p53 tumoral concentrations were found in tumors with
large size, pejorative histological grade and negative ER status. In
contrast, p53 tumoral concentrations were not influenced by menopausal
or PR status. Multivariate Cox analysis demonstrates that tumor size was
the only significant predictor of disease-free survival (P = 0.049) with
a risk factor at 1.38. As regards specific survival, univariate Cox
analysis indicates that p53 taken as a continuous variable is a
significant predictor (P = 0.024) together with histological grade,
tumor size and ER status. In a multivariate Cox analysis there were two
significant and independent variables for predicting overall survival:
tumor size (P = 0.031) and, ER status (P = 0.015) with the highest risk
factor (RR = 2.14). CONCLUSIONS: The present investigation points out
that the prognostic power of p53 tumor determination evaluated at more
than 10 years median survival is not higher than the well-recognized
classic prognostic factors in node-negative breast cancer. The present
data highlight the need to assess the prognostic value of potentially
new biological factors in node-negative breast cancer on cohorts of
patients followed over periods in excess of 10 years.
28
UI - 11809257
AU - Ahr A; Karn T; Solbach C; Seiter T; Strebhardt K; Holtrich U; Kaufmann M
TI -
Identification of high risk breast-cancer patients by gene expression
profiling.
SO - Lancet 2002 Jan 12;359(9301):131-2
We previously used DNA array analyses in the molecular profiling of
breast cancers. By cluster analysis of 55 patients, we identified a
subpopulation of breast cancers-designated class A-that contained a high
number of nodal-positive tumours and that had frequently developed
distant metastases at the time of diagnosis. We have now analysed
follow-up data from these patients. We found that, despite a median of
only 23.5 months of follow-up, 11 of 22 patients in class A progressed
to metastatic disease, and three of five patients classified as having a
nodal status of N0 in this subpopulation developed distant metastases.
Our analysis identifies breast-cancer patients with a high risk of
disease recurrence, and could act as a first step towards improved
patient-adapted therapy.
29
UI - 11873935
AU - Eggerston L
TI -
Ontario defies US firm's genetic patent, continues cancer screening.
SO - CMAJ 2002 Feb 19;166(4):494
30
UI - 11936823
AU - Wohlfahrt J; Olsen JH; Melby M
TI -
Breast cancer risk after childbirth in young women with family history
(Denmark).
SO - Cancer Causes Control 2002 Mar;13(2):169-74
AD - Department of Epidemiology Research, Danish Epidemiology Science Center,
Statens Serum Institut, Copenhagen.
OBJECTIVE: The increased risk of breast cancer in women with family
history of breast cancer (FHBC) might be reduced by early childbirths.
However, childbirth induces a transient increase in risk in the first
5-10 years, which coincides with the relatively increased risk of family
cases at a young age. The objective was to investigate this short-term
change in risk according to FHBC. METHODS: We used a population-based
cohort of 1.5 million Danish women. Between 1968 and 1990, 2770 incident
cases of breast cancer below 40 years of age were identified in the
Danish Cancer Register, of whom 276 (10%) had a FHBC. RESULTS: The first
5 years after a birth the short-term increase in risk was 30% (3-64%)
larger in women with FHBC than without FHBC. After the first 5 years we
observed no difference in the effect of a birth between women with and
without FHBC. CONCLUSIONS: The adverse short-term effect of childbirthis
stronger in women with FHBC.
31
UI - 12015032
AU - Li J; Xu L; He K; Guo W; Zhu X; Zheng Y; Xia P
TI -
[Reversal of nomegestrol acetate on multidrug resistance in
drug-resistant human breast cancer cell line MCF7/ADR]
SO - Zhonghua Zhong Liu Za Zhi 2002 Mar;24(2):129-32
AD - Department of Oncology, Xin Hua Hospital Cancer Center, Shanghai Second
Medical University, Shanghai 200092, China.
OBJECTIVE: To study the reversal effect of nomegestrol acetate (NOM) on
mutidrug resistance (MDR) in MCF7/ADR and its mechanism. METHODS: Using
tetrazolium dye assay, effects of various concentrations of NOM on
sensitivity to ADR in MCF7/ADR was studied. Expression of MDR related
genes MDR1, glutathoine S-transferase Pi (GSTpi), Topoisomerase II alpha
(Topo II alpha) and MDR related protein (MRP) were assayed by reverse
transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry
assay. Using flow cytometry (FCM), intracellular ADR concentration
effects on cell cycle were observed. RESULTS: NOM significantly reversed
MDR in MCF7/ADR. After NOM 20, 10 and 5 micromol/L treatment, the
chemosensitivity to ADR increased to 21, 12 and 8 times. The reversal
activity of NOM was stronger than that of the precursor compound
megestrol acetate, and was comparable to that of verapamail. After
treatment with NOM 5 mic
Cancer Types
Bone Cancer
Brain Tumors
Breast Cancer
Carcinoid Tumors
Endocrine System Cancers
Gastrointestinal Cancers
Gynecologic Cancers
Head and Neck Cancers
Leukemia
Lung Cancers
Lymphomas
Myelomas
Pediatric Cancers
Penile Cancer
Prostate Cancer
Sarcomas
Skin Cancers
Testicular Cancer
Thyroid Cancer
Urinary Tract Cancers
OncoLink Vet
Cancer Treatment
Biologic Therapy
Bone Marrow Transplants
Chemotherapy
Clinical Trials
Complementary Medicine
Gene Therapy
General Treatment Concerns
Hormone Therapy
PDT Center
Proton Therapy
Radiation Oncology
Surgical Oncology
Targeted Therapies
Vaccine Therapies
Cancer Support
Caregivers
Hospice Care and Bereavement
Nutrition and Cancer
Sexuality & Fertility
Side Effects
Support
Survivorship
Exercise and Cancer
Cancer Resources
Cancer News
OncoLink University
Nurses' Notes
Conferences
Newly Diagnosed Patients
Causes and Prevention
Legal and Financial Information for Patients
LGBT Resources
NCI Resources
Global Resources
Cancer Resource List
Resources for Young Adults
OncoLink Media Library
OncoLink TV
Book, Music and Video Reviews
Ask the Experts
Brown Bag Chat
Tracy's Corner
About OncoLink
About OncoLink
Giving to OncoLink
Contact Information
Usage Policy
Editorial Board
How to Partner with OncoLink
Link to OncoLink
Mission Statement
