BRCA1

Epidemiology and Etiology:

· Autosomal dominant inheritance

· High penetrance

· Germline BRCA1 defects (17q21)

· Mutations

· > 500 mutations identified

· BRCA1 function:

· Tumour suppressor

· Transcriptional regulation

· Role in DNA repair (Fanconi anemia complex)

· Interacts with ER

· Role in X inactivation

· Ashkenazi jews

· 2-3% risk of 3 specific mutations

· Breast CA:

· Age of onset 40s to 50s

· No significant increase in risk for males

· risk 60-85%

· development prior to menopause often

· Ovarian CA:

· Risk 20-40%

· Risk of other cancers varies depending on the mutation

Common sites:

· Breast:

· Breast adenocarcinoma

· Ovary:

· Adenocarcinoma

· Prostate

· Adenocarcinoma

· Colon

· Carcinoma

· Pancreas

· carcinoma

Gross features:

·

Histologic features:

· Breast adenocarcinoma

· Medullary (13%) (maybe more if you include NSTs with medullary features?)

· Poorly differentiated

· Mucinous

· Syncitial growth pattern

· Pushing margins

· Lymphocytic response

Immunophenotype:

Marker:	Sensitivity:	Specificity:
BREAST CA:
ER (neg)
PR (neg)
HER2/neu (neg)

Molecular features:

· Genetic testing for BRCA1 mutations

· Difficult because so many mutations have been identified

· Difficult to determine whether a mutation is significant or not

· Breast CA:

· Greater incidence of P53 mutations

· “basal-like” gene expression profile

Other features:

·

References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.