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1. GENETIC FACTORS
BRCA-1
BRCA-2
Li-Fraumini Syndrome
Cowden Disease
Ataxia-Telangiectasia

2. THERAPEUTIC IMPLICATIONS
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Genetic Factors in Breast Cancaer

BRCA-1
Located on chromosome 17
80% are non-sense or frame-shift mutations.
Risk of breast cancer 56% by age 70 (vs. 13% without any genetic predisposition)
Risk of ovarian cancer 16% (vs. 1.6% in non-carriers)
Survival not altered

BRCA-2
Located on chromosome 13
Detected in male breast cancer, female breast cancer, ovarian, pancreatic, prostate, & colon cancer.

Li-Fraumini Syndrome
P53 mutation in 50% of patients

Cowden Disease
Gene localized to chromosome 1
Breast cancer, Thyroid cancer, CNS disease, high-arched palate.

Ataxia-Telangiectasia
Gene localized to chromosome 11
1% of the population may be heterozygote for the gene.
8% of breast cancers below age 40
2% of breast cancers age 40-60

REF= NEJM 336:1401, 1997



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The efficacy of tamoxifen in reducing the incidence of breast cancer among healthy women with BRCA-1 & BRCA-2 mutations:
JAMA 286:2251, 2001: Tamoxifen reduced breast cancer incidence among healthy BRCA-2 carriers by 62%, similar to reduction in incidence of ER-positive breast cancer among all women in the Breast Cancer Prevention Trial. However, tamxifen use beginning at age 35 or older did not reduce breast cancer incidence among healthy women with inherited BRCA-1 mutation.
N=288 women, April 1, 1992-September 30, 1999.
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