Mechanistic Study of Duloxetine in Breast Cancer Patients With Chronic Pain

Inclusion Criteria:

1. Female patients at least 25 years of age

2. Diagnosis of stage 0-III breast cancer within 12 years prior to enrollment. Allindicated surgery, chemotherapy, and/or radiation therapy must have been completed atleast 12 weeks prior to enrollment. Concomitant endocrine therapy and targetedtherapies such as palbociclib, pertuzumab, and trastuzumab are permitted.

3. Pain that developed or worsened since breast cancer diagnosis and is not due toidentifiable traumatic event or fracture

4. Patient-reported worst pain score between 5 and 10 (inclusive) on a 0-10 scale (assessed verbally)

5. Female patients must be at least 1 year postmenopausal or surgically sterile; or mustagree to use a medically acceptable form of contraception

6. Willing to withdraw from selective serotonin reuptake inhibitors (SSRI) and tricyclicantidepressants (TCA) prior to treatment initiation

7. Patients who are currently taking non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, naproxen, meloxicam, gabapentin, pregabalin) and/or opioid painmedications must remain on a stable dosage throughout the duration of the study

8. Able to provide informed consent and willing to sign an approved consent form thatconforms to federal and institutional guidelines.

Exclusion Criteria:

1. Prior use of duloxetine or milnacipran.

2. Prior or current use of venlafaxine specifically for treatment of pain (prior orcurrent use for treatment of other indications, such as hot flashes, is permitted,although cases currently taking venlafaxine must discontinue use prior to studytreatment initiation)

3. Patients must not be taking any contraindicated medications listed on the duloxetinepackage insert including the following: phenothiazines, propafenone, flecainide,linezolid, or anticoagulation medication (e.g., heparin, warfarin, or direct oralanticoagulants); treatment with monoamine oxidase inhibitor within 14 days prior toregistration.

4. Thumbnail abnormalities on either hand (such as due to chemotherapy or trauma, orartificial nails) that are likely to alter pain perception during testing

5. Peripheral sensory neuropathy at the thumbs bilaterally that interferes with functionand/or activities of daily living

6. Significant risk of suicide based on the Investigator's judgment

7. History or behavior that would, in the Investigator's judgment, prohibit compliancefor the duration of the study.

8. History of alcohol or other substance abuse or dependence within the year prior toregistration

9. Known chronic liver disease, end stage renal disease, or creatinine clearance <30mL/min as defined by Cockcroft-Gault equation

10. Uncontrolled narrow-angle glaucoma.

11. Clinically significant coagulation disorder

12. History of seizure disorder

13. Pregnant or breast-feeding. Urine pregnancy test will be assessed at the baselinevisit in women of child-bearing potential with chronic pain.

14. Unable to take oral medications or any medical condition that would interfere with theabsorption of study medication capsules.

15. Currently taking SSRI, serotonin-norepinephrine reuptake inhibitor (SNRI), or TCAregimen (including Wellbutrin) for treatment of major depressive disorder orgeneralized anxiety disorder (without approval and involvement of the patient'streating psychiatrist to taper cases off these medications prior to study treatment). Controls are patients without chronic pain who otherwise meet the following eligibilitycriteria (inclusion #1, 2, 8, exclusion #1, 2, 4, 5, worst pain score 0-1, and notcurrently on medication for pain)