Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers.
OBJECTIVE
To estimate the risk for contralateral breast cancer in members of BRCA1- and BRCA2-positive families and to determine predictive risk factors.


METHODS
A retrospective, multicenter, cohort study was performed from 1996 until 2008 and comprised 2,020 women with unilateral breast cancer (index patients, n = 978; relatives, n = 1.42) from 978 families who had a BRCA1 or BRCA2 mutation. Cox regression analysis was applied to assess the association of age at first breast cancer with time from first to contralateral breast cancer, stratified by the affected BRCA gene.


RESULTS
The cumulative risk for contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI, 38.8% to 56.0%) for patients from families with BRCA1 or BRCA2 mutations. Members of families with BRCA1 mutations had a 1.6-fold (95% CI, 1.2-fold to 2.3-fold) higher risk of contralateral breast cancer than members of families with BRCA2 mutations. Younger age at first breast cancer was associated with a significantly higher risk of contralateral breast cancer in patients with BRCA1 mutation, and a trend was observed in patients with BRCA2 mutation. After 25 years, 62.9% (95% CI, 50.4% to 75.4%) of patients with BRCA1 mutation who were younger than 40 years of age at first breast cancer developed contralateral breast cancer, compared with only 19.6% (95% CI, 5.3% to 33.9%) of those who were older than 50 years of age at first breast cancer.


CONCLUSIONS
Contralateral breast cancer risk depends on age at first breast cancer and on the affected BRCA gene, and this risk should be considered in treatment planning.
Center of Familial Breast and Ovarian Cancer, Department of Gynecology and Obstetrics, University Hospital of Cologne, Cologne, Germany.
Monika K
MK
Graeser
Christoph
C
Engel
Kerstin
K
Rhiem
Dorothea
D
Gadzicki
Ulrich
U
Bick
Karin
K
Kast
Ursula G
UG
Froster
Bettina
B
Schlehe
Astrid
A
Bechtold
Norbert
N
Arnold
Sabine
S
Preisler-Adams
Carolin
C
Nestle-Kraemling
Mohammad
M
Zaino
Markus
M
Loeffler
Marion
M
Kiechle
Alfons
A
Meindl
Dominic
D
Varga
Rita K
RK
Schmutzler
D000328:Adult; D000367:Age Factors; D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary; D010375:Pedigree; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human