Role of Beta-Endorphin in Cancer Therapy Fatigue
Role of Beta-Endorphin in Cancer Therapy Fatigue
The investigators aim to test whether beta-endorphin, a substance our bodies make in response
 to painful and stressful stimuli, plays a causative role in radiation-induced fatigue that
 cancer patients receiving radiation therapy commonly experience. If this is so, the
 investigators' hope is to direct efforts at treating radiation-induced fatigue using agents
 that block the action of beta-endorphin with the aim of improving quality of life for
 patients undergoing radiation therapy
Participants will be breast cancer patients receiving radiation therapy at Massachusetts
 General Hospital. There will be two groups of patients: those receiving adjuvant radiation
 therapy alone following surgical tumor resection, and those receiving adjuvant chemotherapy
 and radiation therapy following surgical tumor resection. Patients receiving any radiation
 regimen detailed below in section 2b are eligible for the study. In this study the
 investigators will be drawing blood for beta-endorphin measurement prior to, at various times
 during, and following patients' treatment regimens. In addition, at each blood draw, patients
 will complete questionnaires that assess fatigue, mood, and pain. These questionnaires have
 all been validated for use in cancer patients (see "Procedures Involving Human Participants
 section below), and for our study, the investigators have formatted them onto computer
 tablets for ease of patient completion and data analysis. This study will progress as
 follows:

 Patients: Patients expected to receive adjuvant radiation therapy at Massachusetts General
 Hospital will be approached for enrollment onto this study. Two groups of patients, a
 chemotherapy group and a non-chemotherapy group, will be enrolled as follows:

 1. Adjuvant chemotherapy followed by radiation therapy

 2. Adjuvant radiation therapy without chemotherapy

 The enrollment goal for each group is 50 patients (total of 100 patients for the study). This
 calculation is based on the approximate number of 30 patients the investigators will need to
 achieve a sensitivity of β-endorphin changes of 5 pM being statistically significant to a
 p-value of<0.05 with 95% power. Based in our finding in mice, the investigators expect
 β-endorphin levels to vary between individuals, and the investigators have increased sample
 size by 70% from our calculations to account for deviations from our β-endorphin levels
 estimations. Additionally, the investigators have added patients to account for a number of
 patient dropping out of the study, since this is a long trial for patients requiring multiple
 blood draws.
Inclusion Criteria:

 1. Age > 18 years

 2. Pathologic diagnosis of stage 0-III breast cancer (any histologic subtype) in either
 breast or both breasts

 3. Previous resection of tumor, either by mastectomy or partial mastectomy, ±sentinel
 lymph node biopsy, ±axillary lymph node dissection

 4. A likelihood of having radiation therapy or chemotherapy following surgery as
 determined by the on-site principal investigator (PI) or co-investigator

 5. Signed informed consent which has been reviewed and approved by the Institutional
 Review Board and no condition that impairs the ability to provide informed consent
 (e.g. uncontrolled psychiatric illness)

 Eligibility for the radiation therapy (RT) alone group will include:

 1. Planned 3-D conformal radiation therapy to the whole breast (2 tangential fields,
 unilateral or bilateral) via standard or Canadian Fractionation, +/- regional nodal
 irradiation.

 2. No planned chemotherapy for this tumor

 Eligibility for the RT + chemotherapy (CT) group will include:

 1. Planned 3-D conformal radiation therapy to the whole breast (2 tangential fields,
 unilateral or bilateral) via standard or Canadian fractionation (photons followed by a
 photon, electron, or mixed photon/electron boost), +/- regional nodal irradiation.

 2. Planned adjuvant chemotherapy (any regimen except for biologic therapy alone)

 Exclusion Criteria:

 1. Continuous/chronic treatment with opiate/opioid analgesics for 3-6 months prior to
 enrollment. In addition, patients receiving radiation therapy alone who have taken
 opiate analgesics from their surgery within 72 hours of the post-surgery/pre-radiation
 therapy blood draw (at 1-6 weeks prior to the start of radiation therapy) will be
 removed from the study. Patients receiving chemotherapy and radiation therapy who have
 taken opiate analgesics from their surgery within 72 hours of the blood draw prior to
 cycle 1 of chemotherapy will be removed from the study.

 2. Prior radiation therapy to the chest or brain

 3. Patients diagnosed with Stage IV breast cancer

 4. History of illegal drug use within 6 months prior to enrollment

 5. At point of enrollment, diagnosis of major depression, bipolar disorder, seasonal
 affective disorder, or anxiety disorder for which the patient is currently taking any
 of the following medications: selective serotonin reuptake inhibitors (SSRIs),
 Tricyclic antidepressants, monoamine oxidase inhibitors, lithium, benzodiazepines,
 barbiturates, drugs acting on the 5-HT receptors. Patients meeting these criteria may
 still enroll in the study if they are on a chronic, stable, low-dose regimen for at
 least 3 months prior to enrollment, as determined by the on-site PIs and
 co-investigating physicians. Patients having to begin on a regimen of any of these
 medications while on the study may continue on the study.

 6. Anemia of any etiology at initial visit (Hct <33%) and the following baseline fatigue
 scores on the Fatigue Symptom Inventory (FSI): Average score for question #s 1-4 > 5;
 and/or Average score for question #s 5-11 > 5. Patients with Hct<33% but who have no
 baseline fatigue (as indicated by baseline scores on the FSI as follows: average score
 for question #s 1-4 < 5 and average scores for question #s 5-11 < 5) are eligible to
 participate.

 7. Endocrine disorders that can cause fatigue: Addison's disease, uncorrected
 hypothyroidism (patients taking thyroid replacement therapy for at least 3 months
 prior to enrollment patients are eligible), central endocrine deficiency,
 polyglandular autoimmune failure.

 8. Patients with thyroid disease (hypothyroidism or hyperthyroidism) that was diagnosed
 within 3 months of cancer diagnosis or patients with previously stable thyroid disease
 who have experienced symptoms or have had to change their medication doses within 3
 months of cancer diagnosis. Patients with stable disease who have no had to change
 medication doses within 3 months of cancer diagnosis. Patients with stable disease who
 have not had to change medication doses within 3 months of cancer diagnosis may enroll
 as long as baseline fatigue scores do not meet criteria for exclusion. Patients
 enrolled in the study who have to alter doses of thyroid medications or who are newly
 diagnosed with thyroid disease while on the study will be removed from the study, and
 will not count towards our total patient accrual.

 9. Uncontrolled autoimmune diseases that can cause fatigue, including fibromyalgia and
 fatigue syndromes. If these are controlled, enrollment or maintenance of the patient
 on the protocol may continue at the discretion of the enrolling principal
 investigator.

 10. Sleep disorder diagnosed within 3 months of enrollment and the following baseline
 fatigue scores on the FSI: Average score for question #s 1-4 > 5; and/or average score
 for question #s 5-11 > 5. Patients diagnosed with a sleep disorder within 3 months of
 enrollment and with FSI scores < 5 on question #s 1-4 and #s 5-11 are eligible.

 11. Activity-limiting heart or lung disease

 12. Renal failure (BUN and creatinine should be within the normal range for the prior 6
 months)

 13. Baseline fatigue as indicated by the following baseline scores on the FSI: Average
 score for question #s 1-4 > 5; and/or Average score for question #s 5-11 > 5.

 14. Patients receiving chemotherapy or radiation therapy at any site other than
 Massachusetts General Hospital

 15. Hepatitis or chronic liver disease (albumin <3 g/dL or >6 g/dL; ALT >60 U/L or < 5
 U/L, AST > 40 U/L or <5 U/L)

 16. Untreated chronic infection (e.g. tuberculosis, osteomyelitis, abscess). Patients
 being treated for these may be enrolled in, or continue on the protocol at the
 discretion of the principal investigators.