Mechanistic Study of Duloxetine Versus Placebo 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. All
indicated surgery, chemotherapy, and/or radiation therapy must have been completed at
least 12 weeks prior to enrollment. Concomitant endocrine therapy and targeted
therapies such as pablociclib, pertuzumab, and trastuzumab are permitted.

3. Pain that developed or worsened since breast cancer diagnosis and is not due to
identifiable 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 must
agree to use a medically acceptable form of contraception

6. Willing to withdraw from selective serotonin reuptake inhibitors and tricyclic
antidepressants prior to treatment initiation

7. Patients who are currently taking non-steroidal anti-inflammatory drugs (e.g.,
ibuprophfen, naproxyen, meloxicam) and/or opioid pain medications 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 that
conforms 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 or
current use for treatment of other indications, such as hot flashes, is permitted,
although cases currently taking venlafaxine must discontinue use prior to study
treatment initiation)

3. Patients must not be taking any contraindicated medications listed on the duloxetine
package insert including the following: phenothiazines, propafenone, flecanide,
linezolid, or anticoagulation medication (e.g., heparin, warfarin, or direct oral
anticoagulants); treatment with MAO inhibitor within 14 days prior to registration.

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

5. Peripheral sensory neuropathy at the thumbs bilaterally that interferes with function
and/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 compliance
for the duration of the study.

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

9. Known chronic liver disease, end stage renal disease, or creatinine clearance <30
mL/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 baseline
visit in women of child-bearing potential with chronic pain.

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

15. Currently taking SSRI, SNRI, or TCA regimen for treatment of major depressive disorder
or generalized anxiety disorder (without approval and involvement of the patient's
treating psychiatrist to taper cases off these medications prior to study treatment).
).

Controls are patients without chronic pain who otherwise meet the following eligibility
criteria (inclusion #1, 2, 8, exclusion #1, 2, 4, 5, worst pain score 0-1, and not
currently on medication for pain)