A comparison of bilateral breast cancers in BRCA carriers.
BACKGROUND
Women with breast cancer and a BRCA mutation have a high risk of developing a contralateral breast cancer. It is generally believed that the two cancers represent independent events. However, the extent of concordance between the first and second tumors with respect to hormone receptor expression and other pathologic features is unknown.


OBJECTIVE
To determine the degree of concordance of estrogen receptor (ER) status, tumor grade, and histology in tumors from women with bilateral breast cancer and a BRCA mutation.


METHODS
Women with a history of bilateral invasive breast cancers were selected from an international registry of women with BRCA1 or BRCA2 mutations. Medical records were reviewed to document the characteristics of each cancer and the treatments received.


RESULTS
Data were available for 286 women with bilateral breast cancer and a BRCA mutation (211 BRCA1; 75 BRCA2). The mean interval between first and second tumor was 5.1 years. The two tumors were concordant more often than expected for ER status (P < 0.0001) and for grade (P < 0.0001), but not for histology (P = 0.55). The ER status of the first tumor was highly predictive of the ER status of the second tumor (odds ratio, 8.7; 95% confidence interval, 3.5-21.5; P < 0.0001). Neither age, menopausal status, oophorectomy nor tamoxifen use was predictive of the ER status of the second tumor.


CONCLUSIONS
There is strong concordance in ER status and tumor grade between independent primary breast tumors in women with a BRCA mutation. The excess concordance may be due to common risk factors, genetic variation, or the existence of a preneoplastic lesion that is common to both tumors.
Weitzel
Jeffrey N
JN
The Centre for Research in Women's Health, 790 Bay Street, Toronto, Ontario, Canada M5G 1N8. steven.narod@sw.ca.
Robson
Mark
M
Pasini
Barbara
B
Manoukian
Siranoush
S
Stoppa-Lyonnet
Dominique
D
Lynch
Henry T
HT
McLennan
Jane
J
Foulkes
William D
WD
Wagner
Teresa
T
Tung
Nadine
N
Ghadirian
Parviz
P
Olopade
Olufunmilayo
O
Isaacs
Claudine
C
Kim-Sing
Charmaine
C
Møller
Pal
P
Neuhausen
Susan L
SL
Metcalfe
Kelly
K
Sun
Ping
P
Narod
Steven A
SA
D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology; D011960:Receptors, Estrogen / Q000032:analysis*; D012307:Risk Factors
D011960:Receptors, Estrogen