The Saethre-Chotzen syndrome is an autosomal, dominantly inherited 
craniosynostosis caused by mutations in the basic helix-loop-helix transcription 
factor gene TWIST1. This syndrome has hitherto not been associated with an 
increased risk of cancer. However, recent studies, using a murine breast tumor 
model, have shown that Twist may act as a key regulator of metastasis and that 
the gene is overexpressed in subsets of sporadic human breast cancers. Here, we 
report a novel association between the Saethre-Chotzen syndrome and breast 
cancer. In 15 Swedish Saethre-Chotzen families, 15 of 29 (52%) women carriers 
over the age of 25 had developed breast cancer. At least four patients developed 
breast cancer before 40 years of age, and five between 40 and 50 years of age. 
The observed cases with breast cancer (n = 15) are significantly higher than 
expected (n = 0.89), which gives a standardized incidence ratio (SIR) of 16.80 
(95% CI 1.54-32.06). Our finding of a high frequency of breast cancer in women 
with the Saethre-Chotzen syndrome identifies breast cancer as an important and 
previously unrecognized symptom characteristic of this syndrome. The results 
strongly suggest that women carriers of this syndrome would benefit from genetic 
counseling and enrolment in surveillance programs including yearly mammography. 
Our results also indicate that the TWIST1 gene may be a novel breast cancer 
susceptibility gene. Additional studies are, however, necessary to reveal the 
mechanism by which TWIST1 may predispose to early onset breast cancer in 
Saethre-Chotzen patients.