Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2.
OBJECTIVE
Women with breast cancer diagnosed early in life comprise a substantial portion of those tested for BRCA1/BRCA2 mutations; however, little information is available on the subsequent risks of contralateral breast cancer in mutation carriers. This study assessed the risk of subsequent contralateral breast cancer associated with carrying a BRCA1 or BRCA2 mutation.


METHODS
In this nested case-control study, patients with contralateral breast cancer diagnosed 1 year or more after a first primary breast cancer (n = 705) and controls with unilateral breast cancer (n = 1,398) were ascertained from an underlying population-based cohort of 52,536 women diagnosed with a first invasive breast cancer before age 55 years. Interviews and medical record reviews were used to collect risk factor and treatment histories. All women were tested for BRCA1/BRCA2 mutations. Relative (rate ratios) and absolute (5- and 10-year cumulative) risks of developing contralateral breast cancer following a first invasive breast cancer were computed.


RESULTS
Compared with noncarriers, BRCA1 and BRCA2 mutation carriers had 4.5-fold (95% CI, 2.8- to 7.1-fold) and 3.4-fold (95% CI, 2.0- to 5.8-fold) increased risks of contralateral breast cancer, respectively. The relative risk of contralateral breast cancer for BRCA1 mutation carriers increased as age of first diagnosis decreased. Age-specific cumulative risks are provided for clinical guidance.


CONCLUSIONS
The risks of subsequent contralateral breast cancer are substantial for women who carry a BRCA1/BRCA2 mutation. These findings have important clinical relevance regarding the assessment of BRCA1/BRCA2 status in patients with breast cancer and the counseling and clinical management of patients found to carry a mutation.
Malone
Kathleen E
KE
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98006, USA. kmalone@fhcrc.org
Begg
Colin B
CB
Haile
Robert W
RW
Borg
Ake
A
Concannon
Patrick
P
Tellhed
Lina
L
Xue
Shanyan
S
Teraoka
Sharon
S
Bernstein
Leslie
L
Capanu
Marinela
M
Reiner
Anne S
AS
Riedel
Elyn R
ER
Thomas
Duncan C
DC
Mellemkjaer
Lene
L
Lynch
Charles F
CF
Boice
John D
JD
Anton-Culver
Hoda
H
Bernstein
Jonine L
JL
D000328:Adult; D000367:Age Factors; D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D011159:Population Surveillance; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human