• Quality of life (i.e., physical well-being, functional well-being, emotional well-being, and social well-being) [ Time Frame: At 12 weeks ]
  Measured by the Total Score of the Functional Assessment Cancer Therapy - General scale (included in the FACIT-F). The FACT-G consists of four subscales: physical well-being (PWB), functional well-being (FWB), emotional well-being (EWB), and social well-being (SWB). Scores on the four subscales are summed to produce a total score ranging from 0 to 108 with higher scores indicating better quality of life. This will be utilized to estimate the indirect (mediation) and direct effects and to obtain bootstrap-based 95% confidence intervals for these effects.
• Depression [ Time Frame: At 12 weeks ]
  Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Depression Short Form 8a. MPlus will be utilized to estimate the indirect (mediation) and direct effects and to obtain bootstrap based 95% confidence intervals for these effects.

• Quality of life [ Time Frame: At 12 weeks ]
  Measured by the Total Score of the Functional Assessment Cancer Therapy ? General scale (included in the FACIT-F). MPlus will be utilized to estimate the indirect (mediation) and direct effects and to obtain bootstrap-based 95% confidence intervals for these effects.
• Depression [ Time Frame: At 12 weeks ]
  Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Depression Short Form 8a. MPlus will be utilized to estimate the indirect (mediation) and direct effects and to obtain bootstrap based 95% confidence intervals for these effects.

• Cognition [ Time Frame: At 12 weeks ]
  Measured by the PROMIS Cognitive Functioning 8a and Cognitive Abilities 4a measures. Will perform mediation analyses.
• Symptomatology [ Time Frame: At 12 weeks ]
  Measured by the M.D. Anderson Symptom Inventory.

PRIMARY OBJECTIVES:

I. To determine the efficacy of bupropion hydrochloride controlled-release (bupropion) versus placebo in reducing fatigue in a double-blinded, placebo-controlled, randomized clinical trial of breast cancer survivors with fatigue.

SECONDARY OBJECTIVES:

I. To assess the efficacy of bupropion versus placebo on depression and quality of life in breast cancer survivors with fatigue.

II. To assess the tolerability of bupropion in breast cancer survivors with fatigue.

EXPLORATORY OBJECTIVES:

I. To assess the efficacy of bupropion versus placebo on symptomatology and cognition in breast cancer survivors with fatigue.

II. To explore the effects of bupropion on putative mechanisms of cancer-related fatigue.

III. To explore associations of CYP2B6 genotype with bupropion metabolism and changes in fatigue.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive bupropion hydrochloride controlled-release orally (PO) once daily (QD) for up to 13 weeks in the absence of unacceptable toxicity.

ARM II: Patients receive placebo PO QD for up to 13 weeks in the absence of unacceptable toxicity.

• Anatomic Stage I Breast Cancer AJCC v8
• Anatomic Stage IA Breast Cancer AJCC v8
• Anatomic Stage IB Breast Cancer AJCC v8
• Anatomic Stage II Breast Cancer AJCC v8
• Anatomic Stage IIA Breast Cancer AJCC v8
• Anatomic Stage IIB Breast Cancer AJCC v8
• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IIIA Breast Cancer AJCC v8
• Anatomic Stage IIIB Breast Cancer AJCC v8
• Anatomic Stage IIIC Breast Cancer AJCC v8
• Cancer Fatigue
• Cancer Survivor
• Complete Remission
• Prognostic Stage I Breast Cancer AJCC v8
• Prognostic Stage IA Breast Cancer AJCC v8
• Prognostic Stage IB Breast Cancer AJCC v8
• Prognostic Stage II Breast Cancer AJCC v8
• Prognostic Stage IIA Breast Cancer AJCC v8
• Prognostic Stage IIB Breast Cancer AJCC v8
• Prognostic Stage III Breast Cancer AJCC v8
• Prognostic Stage IIIA Breast Cancer AJCC v8
• Prognostic Stage IIIB Breast Cancer AJCC v8
• Prognostic Stage IIIC Breast Cancer AJCC v8

• Drug: Bupropion Hydrochloride Controlled-release
  Given PO
  Other Names:

  • Bupropion HCl Controlled-release
  • Bupropion HCl Extended Release
  • Bupropion Hydrochloride Extended-Release
  • Forfivo XL
  • Wellbutrin SR
  • Wellbutrin XL
  • Zyban
• Other: Placebo
  Given PO
  Other Names:

  • placebo therapy
  • PLCB
  • sham therapy
• Other: Quality-of-Life Assessment
  Ancillary studies
  Other Name: Quality of Life Assessment
• Other: Questionnaire Administration
  Ancillary studies

• Experimental: Arm I (bupropion hydrochloride controlled-release)
  Patients receive bupropion hydrochloride controlled-release PO QD for up to 13 weeks in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Bupropion Hydrochloride Controlled-release
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
• Placebo Comparator: Arm II (placebo)
  Patients receive placebo PO QD for up to 13 weeks in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Other: Placebo
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration

Inclusion Criteria:

• Have a diagnosis of stage I-III breast cancer
• Report worst level of fatigue in the past week as moderate to severe (i.e., a score >= 4 on a 0-10 scale, Screening Measures, question 1)
• Have completed surgery, radiation, and/or chemotherapy, at least 2 or more months prior to enrollment (participants can be receiving maintenance, targeted or hormonal therapy)
• Able to read and speak English
• Currently not pregnant or breastfeeding. Women of child-bearing potential must agree to use adequate contraception, i.e, abstinence, IUD (intrauterine device), hormonal contraceptive (birth control pills) or barrier method (condoms) prior to study entry and for the duration of study participation
• Be capable of providing written informed consent

Exclusion Criteria:

• Be currently taking any medications that contain bupropion (e.g., Wellbutrin, Forfivo, Aplenzin, or Zyban
• Be taking a monoamine oxidase inhibitor (MAOI), linezolid, or methylene blue within 2 weeks prior to enrollment
• Be taking any anti-psychotic medications within a week prior to enrollment
• Have a history of renal impairment (i.e., glomerular filtration rate < 45)
• Have a history of cirrhosis (i.e., Child-Pugh score >= 5)
• Have a history of seizures
• Have a history of bulimia or anorexia nervosa
• Report a history of sensitivity to bupropion
• Report an allergy to lactose
• Have a psychiatric or neurological disorder that would interfere with study participation per physician or physician's designee