Clinical trial NCT03000764: RNA and Heat Shock Protein Biomarkers in Radiation-induced Fibrosis in Breast Cancer
Official title: Study of RNA and Heat Shock Protein (HSP) Derived Biomarkers in Radiation-induced Fibrosis in Patients Treated for Breast Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Carcinoma
Fibrosis
Keywords: Skin biopsy
Radiotherapy
RNA biomarker
HSP biomarker
Exon junction array
Gene expression
Radiosensitivity prediction
Lead sponsor: Institut de Cancérologie de Lorraine
Sponsor class: OTHER
First posted: 2016-12-22
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to seeking a molecular signature of pathological radiation induced fibrosis based on the response of skin fibroblasts after irradiation, comparing two groups of patients distinguished by their individual radiosensitivity. The signature will integrate recent insights in terms of alternative splicing of mRNAs and level of expression of non-coding RNAs, particularly long non-coding RNAs, snRNAs, snoRNAs and microRNAs. In each group each expression patterns of candidate HSP proteins potentially predictive of pathological radiation induced fibrosis (HSP27, HSP70, αβ crystalline) in the serum and on cell culture will be characterized.


Eligibility criteria: Inclusion Criteria:

* women
* age ≥ 18 and \<70 years old
* non metastatic disease
* ECOG performance status 0 or 1
* chest size ≤ 110 cm et bra size \<D
* absence of reconstructive breast surgery
* patient able to undergo blood samples (haematological conditions allowing blood sample)
* non-evolving carcinological disease
* absence of systemic inflammatory disease (other than scleroderma) or diabetes
* no inflammatory ou infectious flare on biopsy site at the time of inclusion
* invasive or in situ breast carcinoma
* ability to provide an informed written consent form
* affiliation to a social security system

Then stratification into two groups :

group 1 : radio-sensitive patients

* Post-operative radiotherapy completed at least 6 months ago AND
* radiation induced dermal and/or soft tissue toxicity (dermatitis, fibrosis, atrophy) rated \> 2 (CTCAE v4.0 scale)

group 2 : radio-tolerant (control) patients

* Post-operative radiotherapy completed more than 4 years ago AND
* radiation induced dermal and/or soft tissue toxicity (dermatitis, fibrosis, atrophy) rated ≤1 (CTCAE v4.0 scale) .

Exclusion Criteria:

* age \<18 or \> 70 years old
* evolutive cancer / metastatic disease
* chest size \> 110 cm et bra size ≥ D
* previous reconstructive breast surgery
* ECOG performance status \> 1
* systemic inflammatory disease or diabetes
* inflammatory ou infectious flare on biopsy site at the time of inclusion, very significant ulceration in the treated breast
* anemic patients
* use of oral anticoagulants
* pregnant or likely to be in 6 months
* patients deprived of liberty or under supervision
* non-affiliation to a social security system

Primary outcomes:
measure: Global mRNA alternative splicing and expression of non-coding RNAs profiles in healthy dermal fibroblasts
timeFrame: 6 months
Secondary outcomes:
measure: Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on cultured fibroblasts
timeFrame: 6 months
measure: Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on serum
timeFrame: 6 months
measure: Individual radiosensitivity on healthy dermal fibroblasts
timeFrame: 6 months
measure: Comparison of the overall mRNA splicing and non-coding RNA expression profiles between non irradiated and irradiated dermal fibroblasts in the same individual
timeFrame: 6 months
measure: Changes in cellular distribution of the main non-coding RNAs whose expression varies significantly within the pre-identified signature between the 2 groups of patients
timeFrame: 6 months
measure: seric HSP proteins potentially predictive of pathological induced fibrosis
timeFrame: 6 months
measure: Cellular distribution of specific HSP on fibroblast culture in each group of patients
timeFrame: 6 months
measure: Potential interactions between DNA damage response proteins and candidate HSP
timeFrame: 6 months
Other outcomes:
Locations:
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
Study officials:
affiliation: Institut de Cancérologie de Lorraine
name: VOGIN GUILLAUME, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMR 7365 CNRS-Université de Lorraine, IMoPA
name: BEHM-ANSMANT Isabelle, PhD
role: PRINCIPAL_INVESTIGATOR
References: