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.
Graeser
Monika K
MK
Center of Familial Breast and Ovarian Cancer, Department of Gynecology and Obstetrics, University Hospital of Cologne, Cologne, Germany.
Engel
Christoph
C
Rhiem
Kerstin
K
Gadzicki
Dorothea
D
Bick
Ulrich
U
Kast
Karin
K
Froster
Ursula G
UG
Schlehe
Bettina
B
Bechtold
Astrid
A
Arnold
Norbert
N
Preisler-Adams
Sabine
S
Nestle-Kraemling
Carolin
C
Zaino
Mohammad
M
Loeffler
Markus
M
Kiechle
Marion
M
Meindl
Alfons
A
Varga
Dominic
D
Schmutzler
Rita K
RK
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