Preoperative Image guided Accelerated Partial Breast Irradiation (PAPBI)
in elderly women with early stage Breast cancer; defining radiotherapy sensitivity

Patients with early stage breast cancer are treated with a combination of
surgery, radiotherapy and often with systemic therapy. Radiotherapy is part of
breast conserving therapy and is known to reduce LR rates in all patients with
60-70% although the absolute benefit differs in different subgroups. So far, no
patient groups can be defined in whom radiotherapy would not be necessary. It
is estimated that in approximately half of the patients whole breast
radiotherapy is not necessary, while in others the tumor might be resistant to
radiotherapy. It is likely that tumor cells differ in their response to
radiotherapy and thus influence the LR rate after BCT. If it would be possible
to predict tumor response to radiotherapy, a more tailored treatment can be
advised to individual patients (higher boost dose or primary mastectomy).

This research project is directed at assessing tumor response to radiotherapy.
The goal of the study is to develop a gene expression profile that predicts
response to radiotherapy in early breast cancer patients, allowing for optimal
treatment strategy. When correlations will be seen, the major advantage of such
profiles is to tailor breast cancer treatment. When it is possible to predict
which tumors will recur and which tumor are (non-) responsive to radiotherapy,
patients can be more accurately advised to breast-conserving therapy.

PBI will be performed with image guided external-beam pre-operatively
radiotherapy. We use 3D-IMRT radiotherapy techniques and CT-guided planning
that is widely available and used by radiation oncologists in both academic and
community settings. If successful, this approach would provide a readily
exportable treatment technique.

120 women>=60 years with cT1-2pN0 breast cancer will be given preoperative
PAPBI 10 x 4 Gy (12 days). As the tumor remains *in situ* during irradiation,
accurate tumor delineation and control of accurate radiation dose delivery to
the tumor becomes possible by treating these patients with a cone beam CT
linear accelerator. From biopsies and fine needle aspiration taken of the tumor
before, during radiotherapy and at time of operation RNA and DNA will be
isolated. mRNA gene expression profiles, miRNA expression profiles and DNA copy
number changes associated with response to radiotherapy defined as pathologic
response assessed in the lumpectomy 6 weeks after radiotherapy will be
identified. 60 Patients will be studied as a test set to identify predictive
profiles; 60 patients will be used as a validation set.

Local recurrence (LR) after breast-conserving therapy is age related. Patients
60 years of age and older have a low risk for LR. If a LR occurs, this is
mainly at the original tumorbed (80%). This fact, combined with the addition of
MRI (detects multifocal disease in 11%) to select patients with unifocoal
lesions, holds the LR risk for LR outside the irradiated volume to be very low.

Especially the long treatment period of radiotherapy is aggravating for most
people. The radiation scheme in the proposed study is fairly shorter 2 weeks
(10x) instead of 6 weeks (30x). Also, the irradiated volume of the breast
irradiated is much smaller, which will hold less acute and late toxicity during
and after treatment.

The additional procedures in this study are: biopsies before radiotherapy,
cytology at day 2 and 12 of radiotherapy, MRI before operation. Also, the
sentinel procedure will take place before radiotherapy.