Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type.
OBJECTIVE
BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied.


METHODS
ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America. There were 208 BRCA1 mutation carriers, 88 BRCA2 carriers, and 804 women without a known mutation. We stratified the patients by mutation status, grade, age, and histological type and calculated the percentage of ER-positive tumors within each stratum.


RESULTS
BRCA1 mutation carriers were more likely to have ER-negative breast cancers than were women in other groups, after adjustment for age, grade, and histological subtype (P < 0.001). Only 3.9% of BRCA1-related breast cancers were ER-positive cancers occurring in women in their postmenopausal years. The direction and magnitude of the change in ER status with increasing age at diagnosis in BRCA1 carriers was significantly different from in BRCA2 carriers (P(intercept) = 0.0002, P(slope) = 0.04). Notably, changes in ER status with age at diagnosis for BRCA1 carriers and noncarriers were almost identical (P(slope) = 0.98).


CONCLUSIONS
The strong relationship between the presence of a BRCA1 mutation and the ER-negative status of the breast cancers is neither a consequence of the young age at onset nor the high grade but is an intrinsic property of BRCA1-related cancers. The ER-negative status of these cancers may reflect the cell of origin of BRCA1-related cancers.
Foulkes
William D
WD
Departments of Oncology, Sir M B Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada. william.foulkes@mcgill.ca
Metcalfe
Kelly
K
Sun
Ping
P
Hanna
Wedad M
WM
Lynch
Henry T
HT
Ghadirian
Parviz
P
Tung
Nadine
N
Olopade
Olufunmilayo I
OI
Weber
Barbara L
BL
McLennan
Jane
J
Olivotto
Ivo A
IA
Bégin
Louis R
LR
Narod
Steven A
SA
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology*; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis*
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D011960:Receptors, Estrogen