Breast Cancer

Genetics of the Breast Cancer:

  • Genes Implicated in Hereditary Breast Cancer Syndromes: The medical histories of breast cancer-prone families have been described for over a century. The pattern of breast cancer occurrences in these families is most consistent with an autosomal dominant mode of inheritance. The location of a gene that could explain the pattern of transmission of the breast cancer trait in families averaging early (pre-menopausal) onset of breast cancer was reported in 1990. Since then, two genes have been identified: BRCA1 and BRCA2. Germ-line mutations in these two genes confer susceptibility to breast (female and male) and ovarian cancer, and account for a significant proportion of hereditary breast cancer in two cancer syndromes.  There may be other genetic factors that contribute to hereditary breast cancer, since not all families with multiple cases of breast cancer harbor germ-line BRCA1 or BRCA2 mutations. Host factors (such as lifestyle choices) and other genes may modulate risk of breast cancer in mutation carriers - http://www3.interscience.wiley.com/cgi-bin/fulltext/72500613/PDFSTART

  • A Systematic Review Of Genetic Polymorphisms and Breast Cancer Risk: In this study the authors have identified 46 published case-control studies that have examined the effect of common alleles of 18 different genes on breast cancer risk. Of these, 12 report statistically significant associations, none of which were reported by more than one study. However, many of the studies were small: 10 of the 46 had 80% power or greater to detect a rare allele homozygote relative risk <2.5. We therefore combined the results of individual studies to obtain more precise estimates of risk - http://cebp.aacrjournals.org/cgi/content/full/8/10/843

  • Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer susceptibility: The glutathione S-transferase (GST) family of enzymes function in the body to detoxify carcinogenic compounds. Several genes that code for these enzymes are polymorphic, with particular genotypes previously shown to confer an increased cancer risk. In this study, we investigated the role of three GST genes (GSTM1, GSTP1 and GSTT1) in the development of sporadic breast cancer. Results did not support an involvement of these specific GST gene polymorphisms, either independently or in combination, in susceptibility to sporadic breast cancer in the tested Australian Caucasian population - http://dx.doi.org/10.1016/S0304-3835(00)00361-X

  • Breast cancer risk associated with genotypic polymorphism of the genes involved in the estrogen-receptor-signaling pathway: a multigenic study on cancer susceptibility: The reproductive hormone, estrogen, contributes to the development of breast cancer by binding to the estrogen receptor (ER) in the nucleus, triggering cell growth and tumour promotion. In addition to its role in regulating target genes and signalling pathways involved in cell cycle progression, the ER-signalling pathway may regulate the expression of chromatin-remodelling gene, Metastasis-associated 3 (MTA3), or interact with chromatin-remodelling protein, Metastasis-associated 1 (MTA1). The epidemiological findings of this study highlight the role of newly identified novel ER-related pathways in breast cancer development and provide a more comprehensive picture of the tumorigenic effect of estrogen in breast cancer development - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16502042

  • DNA Copy Number Losses at 1p32-pter in Monozygotic Twins Concordant for Breast Cancer: To find similarities that may possibly indicate novel mutations, we performed comparative genomic hybridization (CGH) analysis following degenerate oligonucleotide primed polymerase chain reaction (PCR) for DNA obtained from unique material of breast cancer that developed in monozygotic twin-pairs. The most frequent loss, detected in half of the abnormal cases, was at 1p32-pter - http://dx.doi.org/doi:10.1016/S0165-4608(98)00274-X

  • High-Resolution Genomic Profiling Reveals Association of Chromosomal Aberrations on 1q and 16p with Histologic and Genetic Subgroups of Invasive Breast Cancer: Invasive ductal carcinoma and invasive lobular carcinoma (ILC) represent the major histologic subtypes of invasive breast cancer. They differ with regard to presentation, metastatic spread, and epidemiologic features. To elucidate the genetic basis of these differences, we analyzed copy number imbalances that differentiate the histologic subtypes. Molecular profiling using bacterial artificial chromosome arrays identified DNA copy number imbalances on 1q and 16p as significant classifiers of histologic and molecular subgroups - http://clincancerres.aacrjournals.org/cgi/content/full/12/2/345

  • Bcl-2 gene family and related proteins in mammary gland involution and breast cancer: Understanding the role Bcl-2 family members play in regulating mammary epithelial cell survival is salient to both normal mammary gland physiology and the development of new therapeutic approaches to breast cancer. Family members are characterized as either pro-apoptotic or anti-apoptotic, depending on cellular context. In addition to its anti-apoptotic effect, Bcl-2 also inhibits progression through the cell cycle - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=99353437&dopt=Abstract

  • Genetics of Breast and Ovarian Cancer - Major Genes Involved: After gender and age, a positive family history is the strongest known predictive risk factor for breast cancer. Hereditary breast cancer is characterized by early age at onset (on average 5-15 years earlier than in sporadic cases), bilaterality, vertical transmission through both maternal and paternal lines, and familial association with tumours of other organs, particularly the ovary and prostate gland. The clinical evidence of an autosomal dominant inherited predisposition to breast cancer has been supported by segregation analysis. The search for genes associated with hereditary susceptibility to breast cancer has been facilitated by the study of large kindreds with multiple affected individuals, and has led to the identification of several susceptibility genes, including BRCA1, BRCA2, TP53, and PTEN/MMAC1 - http://www.cancer.gov/templates/doc.aspx?viewid=6bc9885b-da37-4407-866a-c2c7170fc548&version=HealthProfessional&sectionID=88&#Section_79

  • Genetic Polymorphism and Breast Cancer Risk: Evidence of associations between genetic polymorphisms and breast cancer risk in women has been obtained from case-control or cohort (nested case-control) analytic studies, usually with just a single centre or research group (level of evidence: 3). Results have largely been inconsistent, and none of the markers has had clinical applications - http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page3

Epidemiology of the Breast Cancer:

Screening for Breast Cancer: 

  • Screening for Genetic Risk of Breast Cancer - a comprehensive review: Approximately 10 to 15 percent of all breast cancers are thought to be familial and about one third of these cases are due to an inherited mutation in a BRCA1 or BRCA2 breast cancer susceptibility gene. The lifetime incidence of breast cancer in mutation carriers is above 50 percent, and carriers of BRCA1 mutation also have a substantially increased risk of ovarian cancer. BRCA1 and 2 mutations are associated with early-onset breast cancer, and some experts call for aggressive screening of affected persons. A family history remains the best tool for planning breast cancer surveillance. As experience with BRCA1 and 2 mutations increases, the role of genetic screening may be clarified for both society at large and the medical community - http://www.aafp.org/afp/990101ap/99.html

  • Who is screened for breast cancer by the UK breast screening programme: http://www.cancerhelp.org.uk/help/default.asp?page=3303

Measures:

General Overview:

Genetic Testing:

Hormonal Assays for Breast Cancer:

Screening Tests for Breast Cancer:

Mammography:

Ultrasonography:

Breast Biopsy:

Questionnaires:

Document Provenance and History

Document Author: Dr. Fazal Danish

Document Created: 14th March 2006

Document Edits:

 

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