BRCA1 mutation and young age predict fast breast cancer growth in the Dutch, United Kingdom, and Canadian magnetic resonance imaging screening trials.
OBJECTIVE
Magnetic resonance imaging (MRI) screening enables early detection of breast cancers in women with an inherited predisposition. Interval cancers occurred in women with a BRCA1 mutation, possibly due to fast tumor growth. We investigated the effect of a BRCA1 or BRCA2 mutation and age on the growth rate of breast cancers, as this may influence the optimal screening frequency.


METHODS
We reviewed the invasive cancers from the United Kingdom, Dutch, and Canadian MRI screening trials for women at hereditary risk, measuring tumor size at diagnosis and on preceding MRI and/or mammography. We could assess tumor volume doubling time (DT) in 100 cancers.


RESULTS
Tumor DT was estimated for 43 women with a BRCA1 mutation, 16 women with a BRCA2 mutation, and 41 women at high risk without an identified mutation. Growth rate slowed continuously with increasing age (P = 0.004). Growth was twice as fast in BRCA1 (P = 0.003) or BRCA2 (P = 0.03) patients as in high-risk patients of the same age. The mean DT for women with BRCA1/2 mutations diagnosed at ages < or =40, 41 to 50, and >50 years was 28, 68, and 81 days, respectively, and 83, 121, and 173 days, respectively, in the high-risk group. Pathologic tumor size decreased with increasing age (P = 0.001). Median size was 15 mm for patients ages < or =40 years compared with 9 mm in older patients (P = 0.003); tumors were largest in young women with BRCA1 mutations.


CONCLUSIONS
Tumors grow quickly in women with BRCA1 mutations and in young women. Age and risk group should be taken into account in screening protocols.
Tilanus-Linthorst
Madeleine M A
MM
Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands. m.tilanus-linthorst@erasmusmc.nl
Obdeijn
Inge-Marie
IM
Hop
Wim C J
WC
Causer
Petrina A
PA
Leach
Martin O
MO
Warner
Ellen
E
Pointon
Linda
L
Hill
Kimberley
K
Klijn
Jan G M
JG
Warren
Ruth M L
RM
Gilbert
Fiona J
FJ
D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002170:Canada; D049109:Cell Proliferation; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008403:Mass Screening; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D006113:United Kingdom