This study is open to women who have early-stage breast cancer and are on aromatase inhibitor (AI) therapy, and who have hypoactive sexual desire disorder (HSDD). HSDD is a persistent lack of physical desire for sex and a lack of sexual activity, or even sexual thoughts or fantasies, that causes you distress. The researchers want to determine if sexual functioning, as measured by responses on a sexual functioning questionnaire, is improved by adding Bupropion Extended Release (XL) to the AI treatment regimen. Bupropion XL is an FDA-approved medication for the treatment of major depressive disorder, seasonal affective disorder, and nicotine dependence. It has been studied in HSDD in pre- and post-menopausal healthy women, and has been demonstrated to be effective, but it has not been thoroughly studied in women with early-stage breast cancer on AI therapy.

Patients diagnosed with HSDD (defined as Female Sexual Function Index, or FSFI, score ≤ 26) will discontinue their current AI therapy and will be randomized to treatment with a different AI (non-steroidal AI to steroidal AI, or vice versa) plus bupropion 150 mg orally twice a day versus single-agent AI. All patients diagnosed with HSDD will be referred to counseling services and pelvic floor therapy. In addition, patients will be offered access to the Rosy App. FSFI will be administered at months 1, 3, 6, and during the year 3 visit.

Inclusion Criteria:

• Females 18 or older

• Histologically-proven, resected, hormone receptor-positive (defined as estrogen receptor ≥1% and/or progesterone receptor (PgR)≥1% by immunohistochemistry at local institutions) early invasive breast cancer, stage I-III per American Joint Committee of Cancer (AJCC) 8th edition, regardless of Human Epidermal growth factor Receptor 2 (HER2) status

• Completion of the following planned cancer treatments prior to registration:

  • Surgical resection of breast and nodal surgery; (NOTE: Reconstructive surgery does not have to be completed)
  • Adjuvant radiation therapy, if needed
  • Neoadjuvant and/or adjuvant chemotherapy if needed
  • Treatment with anti-HER2 agents is allowed

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

• Ability to swallow oral medication.

• Provide written informed consent and fill out questionnaires

• Willing to return to the enrolling institution for follow-up

• Women of childbearing potential must not be pregnant or breastfeeding. A negative serum or urine pregnancy test is required per institutional practice guidelines. Women of childbearing potential will be required to use effective contraception from the time of consent until 30 days after the last dose of bupropion. Acceptable methods include hormonal contraception, intrauterine device, barrier methods with spermicide, or sterilization

Exclusion Criteria:

• Previous bilateral oophorectomy or ovarian irradiation; pregnant or lactating at the time of randomization or desiring pregnancy within 5 years.

• History of psychiatric illnesses on active treatment

• History or active suicidal thoughts or behaviors

• Currently taking anti-depressants, anti-anxiety, or anti-psychotic medications. History of seizure disorder

• History of bulimia or anorexia nervosa

• Inhibitors or inducers of CYP2B6

• Drugs metabolized by CYP2D6

• Use of monoamine oxidase inhibitors (MAOI)

• History of hypertension, regardless of control status.

• History of angle closure glaucoma

• Subjects taking levodopa, amantadine, methylene blue, and linezolid

• Those with a hypersensitivity to bupropion, anastrozole, letrozole, exemestane, goserelin, or leuprolide. Currently receiving any of the following cancer-directed therapies:

  • Radiation therapy
  • Systemic therapy such as chemotherapy (standard or investigational)
  • Anti-HER2 agents are allowed