Association of Radiation-induced Lymphocyte Apoptosis with Radiation Induced Fibrosis after Breast Conserving Therapy

Around 5% of all patients treated with breast conserving therapy (BCT) are
affected by a severe form of radiation-induced fibrosis (RIF) of the treated
breast. RIF is characterized by reduced tissue flexibility, reduced compliance
or stricture. There is a large patient-to-patient variability of being at risk
for RIF. The severity of RIF is known to be affected by differences in
treatment characteristics and individual radiosensitivity. An important
biological difference associated with differences in individual
radiosensitivity, is the presence of senescence in cells. Senescence is a
permanent arrest state of the cell division. Senescence can be induced by
Ionizing Radiotherapy (IR) in fibroblasts and other cellular types. The
senescence characteristic of reduced apoptosis can possibly be used to assess
the risk of RIF. The risk of RIF was reported to show a positive correlation
with reduced apoptosis in the Radiation-Induced Lymphocyte Apoptosis (RILA)
assay. Previous studies have shown that a low RILA frequency is associated with
a higher risk of developing RIF.

The primary objective of this study is to assess the univariate association
between RILA frequency and RIF after BCT and radiotherapy among breast cancer
patients. Secondary objectives include: the identification of treatment and
patient related risk factors of developing RIF and the assessment of the
association between RIF and Patient Reported Outcomes (PROs).

Single center non-matched case-control study

The burden for the subject will be in proportion to the potential value of the
research. There will be only one visit with a maximum of one hour to the
outpatient clinic to collect two blood samples and one skin biopsy in the
inframammary fold. A minimal risk of side effects of the blood sample and skin
biopsy is expected. This includes limited pain and hematoma at the biopsy or
venipuncture side. There is a very low risk of infection and hemorrhage after
biopsy. The biopsy side may feel uncomfortable the first days. Also, three well
validated one-time questionnaires (EORTC QLQ-C30, EORTC QLQ-BR23 and BREAST-Q)
will be used to assess the QoL of the participants. The QoL questionnaires will
take 20-25 minutes in total and subjects will complete the questionnaires in
their own time and space.