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Prediction of Adverse Reaction to Radiotherapy in Breast Cancer
Radiotherapy is a very important treatment for breast cancer but a small number of
patients can develop severe side effects. Although fi brosis, telangiectasia and atro-
phy, all contribute to late radiation injury, they have distinct underlying genetic and
radiobiological causes. Fibrosis risk is associated with an infl ammatory response,
whereas telangiectasia is associated with vascular endothelial cell damage. There is
no test at present for an abnormal reaction to radiotherapy. A combined analysis of
two UK breast cancer patient studies shows that 8 % of patients are homozygous for
the TGFβ1 (C-509T) variant allele and have a 15-fold increased risk of fi brosis fol-
lowing radiotherapy (Giotopoulos et al. 2007 ). Atrophy is associated with an acute
response, but the genetic predisposing factors that determine the risk of an acute
response or atrophy have yet to be identifi ed. Identifi cation of the two genes associ-
ated with adverse reaction to cancer treatment means that patients who might react
badly to radiotherapy could be warned in advance or alternative treatments can be
sought. Further research is needed as the genes responsible for redness and peeling
of the skin during treatment have not been found.
Prediction of Recurrence in Breast Cancer for Personalizing Therapy
To tailor local treatment in breast cancer patients there is a need for predicting ipsi-
lateral recurrences after breast-conserving therapy. After adequate treatment (exci-
sion with free margins and radiotherapy), young age and incompletely excised
extensive intraductal component are predictors for local recurrence. Gene expres-
sion profi ling (wound-response signature, 70-gene prognosis profi le (Agendia’s
MammaPrint test) and hypoxia-induced profi le) can identify subgroups of patients
at increased risk of developing a local recurrence after breast-conserving therapy.
Lymph node status at the time of diagnosis of breast cancer is considered to be
the most important measure for future recurrence and overall survival. It is an
imperfect method because a third of patients with no detectable lymph-node involve-
ment will develop recurrent disease within 10 years. DNA microarray analysis of
primary breast tumors and classifi cation to identify a gene expression signature is
strongly predictive of a short interval to distant metastases in patients without tumor
cells in local lymph nodes at time of diagnosis. The poor prognosis signature
consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This
gene expression profi le will be superior to currently used clinical parameters in
predicting disease outcome and selection of patients who would benefi t from adju-
vant therapy. The ability to accurately predict long-term recurrence with microar-
rays, however, might prove very important if subsets of patients who will not relapse
can be spared the toxicity of adjuvant chemotherapy.
Oncotype DX™ Breast Cancer Assay (Genomic Health Inc), a clinically vali-
dated multigene RT-PCR test, is available for use in clinical practice to quantify the
likelihood of breast cancer recurrence for an individual patient. The assay, per-
formed using formalin-fi xed, paraffi n-embedded tissue, analyzes the expression of
10 Personalized Therapy of Cancer