Patients in the TAU group will receive the treatment routinely offered to patients undergoing RT for breast cancer.

Patients in the PSY group will participate to a short-term group psychotherapy with elements of music therapy; meetings will be 1 / week, for a total of 6 weeks. Beginning of psychotherapy intervention will be 1-2 weeks after recruitment at T0 and will therefore cover the entire duration of the RT cycle.

Breast Cancer

Depression, Anxiety

Oxidative Stress

Group psychotherapy with music intervention

Music therapy intervention

Department of Translational Medicine, Università del Piemonte Orientale

Oxidative Stress, Anxiety and Depression in Breast Cancer Patients: Impact of Music Therapy

Analisi Dei Marcatori di Stress Ossidativo in Pazienti Affetti da Tumore Della Mammella, Sottoposte a Radioterapia Postoperatoria e Psicoterapia Con Elementi di Musicoterapia

Anxiety is assessed with the State-Trait Anxiety Inventory 1 and 2 (STAI Y1, STAI Y2), a 40-item self-administered test for the assessment of state and trait anxiety. Each item is rated 1 to 4 (1= not at all, 4= severe); no specific cut-off scores exist. The highest the score, the greater is anxiety.

Depression is assessed with the Montgomery-Asberg Depression Rating Scale (MADRS and with the Beck Depression Inventory (BDI). The MADRS is a 10-item clinician-rated scale for depressive symptoms detection and severity assessment. Each item is rated on a six-point scale, hence 60 is the maximum total score indicating the maximum severity of depressive symptoms. A score <6 points stands for no depression (normal), 7-19 mild depression, 20-34 moderate depression, ≥ 35 severe depression. The BDI is a 21-item self-administered test for the evaluation of subjective depressive feelings or symptoms. It is rated on a 4-points scale (from 0 to 3 according to severity), with the following cutoff values: 0-9 minimal depression, 10-18 mild depression, 19-29 moderate depression, 30-63 severe depression.

GSH measurement was performed through the Glutathione Assay Kit (Cayman Chemical, Ann Arbor, MI, USA). For the experiments, each plasma sample was deproteinated and centrifuged at 2000 g for 2 min. Fifty μl of the samples was transferred to a 96‐well plate where GSH was detected through a spectrophotometer (VICTOR™ X Multilabel Plate Reader), at excitation/emission wavelengths of 405-414 nm. To ensure accurate GSH quantification (expressed as µM), a reference curve with the GSH Standard was prepared (range of known GSH concentration: 0-16 μM). As regards the performance of the assay, variation coefficient of 3.6% for inter-assay and 1.6% for intra-assay is reported.

TBARS were determined as malonyldialdeide (MDA) release. MDA measurement was performed by using the TBARS assay Kit (Cayman Chemical). For the experiments, 100 µl of each plasma sample was added to 100 µl of sodium dodecyl sulfate (SDS) solution and 2 ml of the Color Reagent. After centrifugation, 150 μl of each sample was transferred to a 96‐well plate where MDA was detected through a spectrophotometer (VICTOR™ X Multilabel Plate Reader), at excitation/emission wavelengths of 530-540 nm. In order to quantify the correct values of TBARS (expressed as µM MDA), a reference standard curve was prepared (range of known TBARS concentration: 0-50 μM). As regards the performance of the assay, intra-coefficient of variation of 5.5% and an inter-coefficient variation of 5.9% is reported.

Resilience is assessed with the Resilience Scale for Adults (RSA). This is a 33-item self-administered scale evaluating intra- or inter-relational stress preventing factors (positive self-perception, positive future perception, social competence, structured style, family cohesion and social resources). The higher is the total score, the greater is the subject's resilience.

Quality of life is assessed with the Short Form-36 (SF-36), a self-administered test assessing health-related quality of life, both from a somatic and psychological standpoint. It assesses several sub-areas: physical activity, role and physical health, physical pain, general health, vitality, social activities, role and emotional state, mental health and health change. Results are expressed in age- calculated percentiles.

IL-6 measurement was performed by using the Human IL-6 ELISA kit (Invitrogen Carlsbad, California, USA). For the experiments, 50 μl of each plasma sample and 50 μl of Assay Buffer 1X were added to each well, with 50 μl of Biotin-Conjugate and incubated at room temperature (RT) on microplate shaker for 2 h. After addition of 400 μl Wash Buffer, 100 μl Streptavidin-HRP and 100 μl Substrate Solution, each well was incubated for 10 min at RT in the dark. The enzyme reaction was stopped by adding 100 μl Stop Solution, and IL-6 was detected through a spectrophotometer (VICTOR™ X Multilabel Plate Reader), using a wavelength of 450 nm. In order to quantify the correct value of IL-6 in each sample (expressed as pg/ml), a reference standard curve was prepared (range of IL-6 standard concentration:0-20 pg/mL). As regards the performance of the assay, intra-coefficient of variation of 8.5% and an inter-coefficient variation of 9.8% is reported. The sensitivity of the test is < 1 pg/ml.

TNFα measurement was performed with the Human TNF alpha ELISA kit (Invitrogen, Carlsbad, California, USA). For the experiments, 50 μl of each plasma sample and 50 μl of Sample Diluent were added to each well, with 50 μl of Biotin-Conjugate and incubated at RT on microplate shaker for 2 h. After addition of 400 μl Wash Buffer, 100 μl Streptavidin-HRP and 100 μl Substrate Solution, each well was incubated for 10 min at RT in the dark. The enzyme reaction was stopped by adding 100 μl of Stop Solution and each well was read immediately. TNFα was detected through a spectrophotometer (VICTOR™ X Multilabel Plate Reader), using a wavelength of 620 nm. To quantify the correct value of in each sample, a reference standard curve was prepared (range of TNFα standard concentration: 0-100 pg/mL). As regards the performance of the assay, intra-coefficient of variation of 3.4% and inter-coefficient variation of 5.2% is reported. The sensitivity of the test is 0.13 pg/ml.

HPLC analysis of retinol, α and γ -tocopherol, lycopene and β carotene were carried out on Agilent 1200 series HPLC.
200 ml of each plasma sample was mixed with 300µl of water and 500 µl of ice-cold absolute ethanol and immediately vortexed for 10 s. Two millilitres of ice-cold hexane was added. The mixture was immediately vortexed for 2 minutes and then centrifuged at 3000 g for 1 min and 1 ml of the upper (organic) layer was transferred in a vial, evaporated to dryness under a nitrogen stream and reconstituted with 100 ml of a mixture of acetonitrile/dichloromethane/methanol for HPLC analysis.
Twenty microlitres of this mixture were then injected and the antioxidants were eluted with a mobile phase containing acetonitrile/dichloromethane/methanol, glacial acetic acid (1 g /l) at a constant flow of 1.8 ml/min.
Detection of lipid soluble antioxidants was performed at specific wavelength: retinol (326 nm), γ- and α-tocopherol (292nm), lycopene and β-carotene (460nm).

Colesterol and high sensitivity C-reactive Protein (CRP) were analyzed on ADVIA® 1800 Clinical Chemistry Analyzer (Siemens Healthcare Diagnostics), by automated methods and certified kits.
Colesterol (range:0 - 200 mg/dL) High sensitivity C-reactive Protein (range:0 - 1 mg/dL)

Marco Krengli

Full Professor

Università degli Studi del Piemonte Orientale "Amedeo Avogadro"

Patients in this arm will receive 400mg of celecoxib once daily. In addition, Hormone Receptor (+) patients will receive endocrine treatment according to local practice.

Patients in this arm will receive 2 tablets once daily. In addition Hormone Receptor (+) patients will receive endocrine treatment according to local practice.

Patients in this arm will receive 400mg of celecoxib once daily. In addition, Hormone Receptor (+) patients will receive endocrine treatment according to local practice.
Celecoxib: Patients will receive 400mg of Celecoxib once daily for two years or until disease progression (if before the two years limit) or until development of unacceptable toxicities. In addition ER(+) patients will receive endocrine treatment according to local practice.

Celecoxib

Patients in this arm will receive 2 tablets once daily. In addition Hormone Receptor (+) patients will receive endocrine treatment according to local practice.
Placebo: Two capsules once daily with food

Placebo

Total

Sex: Female, Male

Race/Ethnicity, Customized

From time of randomisation to the date of first event; with events contributing to the analysis defined as loco-regional and distant breast cancer recurrence, new primary breast cancer (ipsilateral or contralateral) and death without disease relapse (intercurrent death)

Disease Free Survival (DFS) Benefit of Two Years Adjuvant Therapy With the COX-2 Inhibitor Celecoxib Compared With Placebo in Primary Breast Cancer Patients.

First local recurrence and first distant recurrence will be recorded on separate parts of the CRF. In the event of local progression, all patients must be followed up for distant recurrence, second malignancy and survival. Similarly in the case of second malignancy, the appropriate CRF should be completed and patients should REACT Protocol, Version 39, dated 01.11.2016 Page 34 of 48 continue to be followed for disease progression and where possible the relation of any subsequent disease progression and/or death due to the primary or second cancer should be established.

Overall Survival

Any malignant contralateral breast disease will be included and recorded as a second primary

Number of Participants With Incidence of Second Primary Breast Cancers

Number of deaths recorded as having cardiovascular involvement are reported by treatment group.

Cardiovascular Mortality

Overall Study

Prof Charles Coombes

Patients will receive 400mg of Celecoxib once daily for two years or until disease progression (if before the two years limit) or until development of unacceptable toxicities. In addition ER(+) patients will receive endocrine treatment according to local practice.

REACT Trial Information linked to the sponsor webpage

phospholipase/brystkræft

Oxidative Stress, Anxiety and Depression in Breast Cancer Patients: Impact of Music Therapy

European Celecoxib Trial in Primary Breast Cancer

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