The prevalence of BRCA1 mutations among young women with triple-negative breast cancer.
BACKGROUND
Molecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer. Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative for estrogen-receptor, progesterone-receptor and HER2). The decision to offer genetic testing to a breast cancer patient is usually based on her family history, but in the absence of a family history of cancer, some women may qualify for testing based on the age-of-onset and/or the pathologic features of the breast cancer.


METHODS
We studied 54 women who were diagnosed with high-grade, triple-negative invasive breast cancer at or before age 40. These women were selected for study because they had little or no family history of breast or ovarian cancer and they did not qualify for genetic testing using conventional family history criteria. BRCA1 screening was performed using a combination of fluorescent multiplexed-PCR analysis, BRCA1 exon-13 6 kb duplication screening, the protein truncation test (PTT) and fluorescent multiplexed denaturing gradient gel electrophoresis (DGGE). All coding exons of BRCA1 were screened. The two large exons of BRCA2 were also screened using PTT. All mutations were confirmed with direct sequencing.


RESULTS
Five deleterious BRCA1 mutations and one deleterious BRCA2 mutation were identified in the 54 patients with early-onset, triple-negative breast cancer (11%).


CONCLUSIONS
Women with early-onset triple-negative breast cancer are candidates for genetic testing for BRCA1, even in the absence of a family history of breast or ovarian cancer.
Young
S R
SR
Women's College Research Institute, Department of Public Health, The University of Toronto, Toronto, Canada. sryoung37@aol.com
Pilarski
Robert T
RT
Donenberg
Talia
T
Shapiro
Charles
C
Hammond
Lyn S
LS
Miller
Judith
J
Brooks
Karen A
KA
Cohen
Stephanie
S
Tenenholz
Beverly
B
Desai
Damini
D
Zandvakili
Inuk
I
Royer
Robert
R
Li
Song
S
Narod
Steven A
SA
D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D055815:Young Adult
D019313:BRCA1 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone