Supplementation With Dietary Anthocyanins and Side Effects of Radiotherapy for Breast Cancer
Supplementation With Dietary Anthocyanins and Side Effects of Radiotherapy for Breast Cancer
Attention has been focused recently on the development of modalities that can protect healthy
 organs from the harmful effects of radiation applied during different cancer treatment
 schedules. As radiation-induced DNA damage involves oxidative stress, the protective role of
 antioxidants has been tested in different dietary studies. Previous experience by the
 collaborative team of the principal investigator and radiotherapists at the Catholic
 University of Campobasso has shown in a retrospective study that moderate wine consumption
 can reduce the side-effects of radiation therapy in patients with breast cancer. This effect
 was presumably due to the polyphenol non alcoholic fraction of wine, a finding in agreement
 with a cross-over intervention study in adult male volunteers, on protection by
 de-alcoholized red wine from ex vivo radiation-induced DNA damage.

 The purpose of this clinical trial will be to test the impact of supplementation with
 anthocyanin-enriched food on the acute and medium-term side effects of radiotherapy in breast
 cancer patients, in a prospective study design. Therefore a double blind, randomised,
 placebo-controlled clinical trial will be organised by assigning patients with breast cancer
 scheduled for radiotherapy to a diet supplemented with an anthocyanin soluble extract.
Detailed Description

 1. Study Rationale:

 Attention has been focused recently on the development of modalities that can protect
 healthy organs from the harmful effects of radiation applied during different cancer
 treatment schedules. As radiation-induced DNA and cellular damage involve oxidative
 stress, the protective role of antioxidants will be tested on the toxic condition
 induced by radiotherapy in breast cancer treatment. Consumption of polyphenol-rich
 foods, such as fruits and vegetables, and beverages derived from plants, such as cocoa,
 red wine and tea, may represent a beneficial diet in terms of oxidative protection.
 Indeed, a retrospective study reports that that moderate wine consumption can reduce the
 side-effects of radiation therapy in patients with breast cancer. This effect was
 presumably due to the polyphenol non alcoholic fraction of wine, a finding in agreement
 with a cross-over intervention study in adult male volunteers, on protection by
 de-alcoholized red wine from ex vivo radiation-induced DNA damage. However, there are no
 studies that address the relationship of polyphenol-rich food consumption with the toxic
 effects of radiations in patients undergoing radiotherapy for breast cancer treatment.

 2. Aim of the study. The main objectives of this study are to evaluate the association
 between the effect of polyphenol-rich food supplementation and toxicity of radiotherapy
 for breast cancer.

 3. Study design: Randomized, placebo-controlled double-blind trial with 2 parallel arms:
 soluble corn flour at high content in anthocyanins and placebo. Placebo consists of
 soluble corn flour poor in anthocyanins. The treatment will start one week before
 starting radiotherapy, and continue during all radiotherapy treatment (of 3 or 5 weeks).

 4. Study Population and recruitment: A total of 300 consecutive breast cancer patients
 eligible for radiotherapy. Participants will be identified at the Department of
 Radiotherapy of the Giovanni Paolo II Foundation of Campobasso.

 Eligible subjects will be recruited at their first consultation and subsequently referred to
 the research investigators. The research staff in charge of the recruitment will pre-screen
 participants on the basis of inclusion/exclusion criteria and will explain the study at this
 time.
Inclusion Criteria:

 1. The patient must consent to be in the study and must have signed an approved consent
 form conforming with institutional guidelines.

 2. Patients must be ≥ 18 years old.

 3. On histological examination, the tumor must be DCIS or invasive carcinoma of the
 breast.

 4. Surgical treatment of the breast must have been lumpectomy or quadrantectomy. The
 margins of the resected specimen must be histologically free of tumor (DCIS and
 invasive). Reexcision of surgical margins is permitted.

 5. Patients with invasive breast cancer are required to have axillary staging which can
 include sentinel node biopsy alone (if sentinel node is negative), sentinel node
 biopsy followed by axillary dissection or sampling with a minimum total of 6 axillary
 nodes (if sentinel node is positive), or axillary dissection alone (with a minimum of
 6 axillary nodes). (Axillary staging is not required for patients with DCIS.)

 6. The patient must be randomized within 45 days following the last surgery for breast
 cancer (lumpectomy, re-excision of margins, or axillary staging procedure) or within
 30 days following the last chemotherapy cycle.

 7. Patients with a history of non-breast malignancies are eligible if they have been
 disease-free for 5 or more years prior to randomization and are deemed by their
 physician to be at low risk for recurrence. Patients with the following cancers are
 eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the
 cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous
 cell carcinoma of the skin.

 Exclusion Criteria:

 1. Axillary nodes with definite evidence of microscopic or macroscopic extracapsular
 extension.

 2. One or more positive non-axillary sentinel node(s). (Note that intramammary nodes are
 staged as axillary nodes.)

 3. Palpable or radiographically suspicious ipsilateral or contralateral axillary,
 supraclavicular, infraclavicular, or internal mammary nodes, unless there is
 histologic confirmation that these nodes are negative for tumor.

 4. Suspicious microcalcifications, densities, or palpable abnormalities (in the
 ipsilateral or contralateral breast) unless biopsied and found to be benign.

 5. Non-epithelial breast malignancies such as sarcoma or lymphoma.

 6. Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or
 separated by 4 or more centimeters.

 7. Paget's disease of the nipple.

 8. Synchronous bilateral invasive or non-invasive breast cancer.

 9. Surgical margins that cannot be microscopically assessed or are positive at pathologic
 evaluation. (If surgical margins are rendered free of disease by reexcision, the
 patient is eligible.)

 10. Breast implants. (Patients who have had implants removed are eligible.)

 11. Prior breast or thoracic radiation therapy for any condition.

 12. Collagen vascular disease, specifically dermatomyositis with a creatine phosphokinase
 level above normal or with an active skin rash, systemic lupus erythematosus, or
 scleroderma.

 13. Pregnancy or lactation at the time of proposed randomization. Women of reproductive
 potential must agree to use an effective non-hormonal method of contraception during
 therapy.

 14. Psychiatric or addictive disorders or other conditions that, in the opinion of the
 investigator, would preclude the patient from meeting the study requirements.