Hereditary breast cancer

2000-11-01 Kaija Holli Affiliation

Department of Palliative Medicine, Department of Oncology, Tampere University Hospital, Tampere, Finland

Identity

Name

Alias

Site-specific breast cancer , Familiar breast-ovarian cancer

Note

hereditary or familiar form of breast cancerwith a familiar background

Inheritance

follows an autosomal dominant pattern ,

5-10 % of all breast cancers have hereditary background ,

hereditary susceptibility for breast cancer has been counted to be 30-40 % of BRCA1 (see below, gene section), 10-30 % of BRCA2, less than 1 % of Tp 53, less than 1 % of PTEN and one third of unknown mutations; frequency of BRCA1 mutation is around 0.2 % in general population, 200 carriers among 100 000 individuals.

Omim

114480

Mesh

D001943

Orphanet

227535 Hereditary breast cancer

Umls

Clinics

Phenotype and clinics

\"site specific breast cancer\" is characterized by the predominance of breast cancer, while \"hereditary breast-ovarian cancer\" has neoplasms in both organs

BRCA1 mutation carrier (chromosome 17q12-21) has early age at onset, and lifetime risk for breast cancer 50 % - 85 % and ovarian cancer 15 %-45 %; about 500 different mutations have been reported; possible increased risk of prostate cancer and colon cancer

BRCA2 (chromosome 13q12-13) mutation carrier has risk for breast cancer 30 %-85 %; about 300 different mutations have been reported; it is also associated for male breast cancer (6 %) and ovarian breast cancer (10% -20%); increased risk of prostate, laryngeal cancer and pancreatic cancer.

other genetic conditions associated with increased breast cancer risk are:

Li-Fraumeni syndroma (p53 mutation on chromosome 17p13) is characterized by very early onset of neoplasms, including soft tissue sarcoma, osteosarcoma, brain tumours, leukemia, lung cancer, laryngeal cancer and adrenocorteal cancer.; lifetime risk for cancer: about 90 % for women and 70 % for men

Cowden syndroma (PTEN, 10q23) is a rare type of autosomal dominant inherited condition of multiple hamartomas with increased risk of bilateral breast cancers and thyroid tumours

Muir-Torre Syndroma ( MSH2 , MLH1), with also cancers of the gastro intestinal (GI)-tract, skin, genito urinary (Gu)-system

Peutz-Jeghers Syndroma, with also abnormal melarin deposits, GI-polyposis, cancers of the GI-tract, uterus, ovary and testis.

Ataxia-teleangiectasia (linked to chromosome 11q21) autosomal recessive disorder with many clinical signs including increased risk for breast cancer; homozygous AT carriers have around 100-fold risk of cancer

one third of familiar breast cancers with hereditary background is still unknown; recent findings indicated that genotyping \"BRCA3\" locus at 13q and \"BRCA2\" locus at 2q may lead identifing the next mutations.

breast cancers of BRCA1 and, to lesser extent BRCA2 carriers differ from those of sporadic breast cancers: more high-grade tumours, pleomorphism, a higher mitotic count, less tubule formation, more often steroid receptor negative, DNA-aneuploid and more often higher s-phase fractions.

Treatment

prophylactic bilateral mastectomy (reduces the risk of about 90 %) and\/or ovarian ablation. Chemoprevention (antiestrogens, aromataze inhibitors, retinoids) mainly in clinical trials (tamoxifen may reduce the risk about 45 %).

Pubmed ID	Last Year	Title	Authors
9167459	1997	Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Breast Cancer Linkage Consortium.
7825587	1995	Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium.	Easton DF et al
8870999	1996	Prophylactic mastectomy for genetic predisposition to breast cancer: the proband's story.	Eeles R et al
8071972	1994	Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy?	Eng C et al
9747868	1998	Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.	Fisher B et al
9634504	1998	Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients.	Fodor FH et al
9497246	1998	Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.	Ford D et al
10944226	2000	Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus.	Kainu T et al
8601560	1996	Hereditary cancer: two hits revisited.	Knudson AG et al
9701363	1998	Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations.	Lakhani SR et al
10359546	1999	Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer.	Peto J et al
9145676	1997	The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.	Struewing JP et al
9802270	1998	Population-based study of risk of breast cancer in carriers of BRCA2 mutation.	Thorlacius S et al

External Links

Citation

Kaija Holli

Hereditary breast cancer

Atlas Genet Cytogenet Oncol Haematol. 2000-11-01

Online version: http://atlasgeneticsoncology.org/cancer-prone-disease/10062/hereditary-breast-cancer

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