Radiation-associated breast tumors display a distinct gene expression profile.
OBJECTIVE
Women who received irradiation for Hodgkin's lymphoma have a strong increased risk for developing breast cancer. Approximately 90% of the breast cancers in these patients can be attributed to their radiation treatment, rendering such series extremely useful to determine whether a common radiation-associated cause underlies the carcinogenic process.


METHODS
In this study we used gene expression profiling technology to assess gene expression changes in radiation-associated breast tumors compared with a set of control breast tumors of women unexposed to radiation, diagnosed at the same age. RNA was obtained from fresh frozen tissue samples from 22 patients who developed breast cancer after Hodgkin's lymphoma (BfHL) and from 20 control breast tumors.


RESULTS
Unsupervised hierarchical clustering of the profile data resulted in a clustering of the radiation-associated tumors separate from the control tumors (p < 0.001). Using a supervised class prediction tool, a nearest centroid classifier of 198 probes was identified. The BfHL tumors were often of the intrinsic basal breast tumor subtype, and they showed a chromosomal instability profile and a higher expression of the proliferation marker Ki-67.


CONCLUSIONS
These results indicate that radiation-associated tumors are different from other breast tumors on the basis of their expression profile and that they are mainly of one specific cause that is characterized by high proliferation and a more aggressive tumor type.
Broeks
Annegien
A
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Braaf
Linde M
LM
Wessels
Lodewyk F A
LF
van de Vijver
Marc
M
De Bruin
Marie L
ML
Stovall
Marilyn
M
Russell
Nicola S
NS
van Leeuwen
Flora E
FE
Van 't Veer
Laura J
LJ
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D002278:Carcinoma in Situ / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000235:genetics; D018275:Carcinoma, Lobular / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006689:Hodgkin Disease / Q000532:radiotherapy*; D006801:Humans; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*