Hereditary breast cancer: part I. Diagnosing hereditary breast cancer syndromes.
Hereditary breast cancer (HBC) accounts for as much as 10% of the total BC burden. Most of these cases will be found to be due to a BRCA germline mutation. An estimated additional 15-20% of those affected with BC will have one or more first- and/or second-degree relatives with BC. Therefore, when these numbers are combined, familial BC risk accounts for approximately 20-25% of the total BC burden. However, because of the often limited information on family history in the etiologic assessment of BC, this may be an underestimate. Confounding factors include its phenotypic and genotypic heterogeneity, given the association of HBC with a plethora of differing cancer syndromes. Its most common occurrence is its association with ovarian cancer in the so-called hereditary breast-ovarian cancer syndrome due to BRCA1 and BRCA2 mutations. More rarely, it occurs in the Li-Fraumeni syndrome, caused by a p53 germline mutation, in which markedly early-onset BC is found in association with brain tumors, sarcomas, leukemia, lymphoma, malignant melanoma, and adrenal cortical carcinoma. Importantly, the age-adjusted incidence of BC in women in the United States fell sharply, by 6.7%, in 2003, when compared with the rate identified in 2002. We postulate that increasing knowledge about the genetics of BC may have partially contributed to the identification of high-risk patients who thereby may have benefited significantly from early diagnosis.
Lynch
Henry T
HT
Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska 68178, USA. htlynch@creighton.edu
Silva
Edibaldo
E
Snyder
Carrie
C
Lynch
Jane F
JF
D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D005817:Genetic Counseling; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human