BRE-06: Study to Increase Tolerance to Aromatase Inhibitors for Patients With Early-Stage Hormone Receptor Positive Breast Cancer Who Developed Hypoactive Sexual Desire Disorder

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Hypoactive Sexual Desire Disorder; Hormone Receptor Positive Breast Carcinoma; Early-stage Breast Cancer
• Intervention / Treatment: Drug: Aromatase Inhibitors; Drug: GnRH agonist; Drug: Bupropion

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Oana Danciu, MD; Phone Number: (312) 355-1625; Email: ocdanciu@uic.edu
• Study Contact Backup: Name: Michelle Karan; Phone Number: (224) 563-7137; Email: makaran2@uic.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
      • Principal Investigator: Oana Danciu, MD
      • Contact: Oana Danciu, MD; Phone Number: (312) 355-1625; Email: ocdanciu@uic.edu
      • Contact: Michelle Karan; Phone Number: (224) 563-7137; Email: makaran2@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single Agent Aromatase Inhibitor and Gonadotropin-Releasing Hormone (GnRH) Agonist; Participants will receive aromatase inhibitor as part of standard of care for early stage breast cancer. The duration of AI therapy will be at the discretion of the investigator. Patients who are diagnosed with Hypoactive Sexual Desire Disorder at baseline will discontinue their current aromatase inhibitor treatment and switch to a different aromatase inhibitor treatment (i.e., non-steroidal AI to steroidal AI, or vice versa). Those who are pre-menopausal will also be treated with ovarian suppression therapy (in the form of a GnRH agonist) per standard of care. They will be treated by subcutaneous injection every 28 days and the type, duration, and dose of drug will be per the treating physician's discretion. Those who have ongoing Hypoactive Sexual Desire Disorder symptoms have the option to crossover to the bupropion arm.	Drug: Aromatase Inhibitors; An aromatase inhibitor will be given at a duration, frequency, and dose per standard of care.; Other Names: Exemestane; Letrozole; Anastrozole; Drug: GnRH agonist; A GnRH agonist will be administered for a duration and dose per standard of care as part of ovarian suppression therapy for those who are pre-menopausal. These will be administered subcutaneously every 28 days.; Other Names: Leuprolide; Goserelin
Active Comparator: Single Agent Aromatase Inhibitor; Participants will receive aromatase inhibitor as part of standard of care for early stage breast cancer. The duration of AI therapy will be at the discretion of the investigator. Patients who are diagnosed with Hypoactive Sexual Desire Disorder at baseline will discontinue their current aromatase inhibitor treatment and switch to a different aromatase inhibitor treatment (i.e., non-steroidal AI to steroidal AI, or vice versa). Those who have ongoing Hypoactive Sexual Desire Disorder symptoms have the option to crossover to the bupropion arm.	Drug: Aromatase Inhibitors; An aromatase inhibitor will be given at a duration, frequency, and dose per standard of care.; Other Names: Exemestane; Letrozole; Anastrozole
Experimental: Single Agent Aromatase Inhibitor, Gonadotropin-Releasing Hormone (GnRH) Agonist, and Bupropion; Participants will receive aromatase inhibitor as part of standard of care for early stage breast cancer plus bupropion 150 mg orally twice daily. The duration of AI therapy will be at the discretion of the investigator. Patients who are diagnosed with Hypoactive Sexual Desire Disorder at baseline will discontinue their current aromatase inhibitor treatment and switch to a different aromatase inhibitor treatment (i.e., non-steroidal AI to steroidal AI, or vice versa). Patients with Hypoactive Sexual Desire Disorder will also have the option to change their dose to 300 mg orally once a day. Those who are pre-menopausal will also be treated with ovarian suppression therapy (in the form of a GnRH agonist) per standard of care. They will be treated by subcutaneous injection every 28 days and the type, duration, and dose of drug will be per the treating physician's discretion.	Drug: Aromatase Inhibitors; An aromatase inhibitor will be given at a duration, frequency, and dose per standard of care.; Other Names: Exemestane; Letrozole; Anastrozole; Drug: GnRH agonist; A GnRH agonist will be administered for a duration and dose per standard of care as part of ovarian suppression therapy for those who are pre-menopausal. These will be administered subcutaneously every 28 days.; Other Names: Leuprolide; Goserelin; Drug: Bupropion; Bupropion will be taken twice a day by mouth at 150 mg with the option to change to 300 mg daily for those with ongoing HSDD symptoms; Other Names: Wellbutrin; Zyban
Experimental: Single Agent Aromatase Inhibitor and Bupropion; Participants will receive aromatase inhibitor as part of standard of care for early stage breast cancer plus bupropion 150 mg orally twice daily. The duration of AI therapy will be at the discretion of the investigator. Patients who are diagnosed with Hypoactive Sexual Desire Disorder at baseline will discontinue their current aromatase inhibitor treatment and switch to a different aromatase inhibitor treatment (i.e., non-steroidal AI to steroidal AI, or vice versa). Patients with Hypoactive Sexual Desire Disorder will also have the option to change their dose to 300 mg orally once a day.	Drug: Aromatase Inhibitors; An aromatase inhibitor will be given at a duration, frequency, and dose per standard of care.; Other Names: Exemestane; Letrozole; Anastrozole; Drug: Bupropion; Bupropion will be taken twice a day by mouth at 150 mg with the option to change to 300 mg daily for those with ongoing HSDD symptoms; Other Names: Wellbutrin; Zyban

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance of study drugs in patients with early stage breast cancer and Hypoactive Sexual Desire Disorder	To compare the tolerance of aromatase inhibitor (+/- ovarian suppression therapy) in comparison to aromatase inhibitor (+/- ovarian suppression therapy) plus bupropion. This is assessed by the proportion of patients no longer meeting HSDD criteria as reflected by FSFI > 26 at three months post-randomization.	Until 3 months post-study enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free-survival in patients with early stage breast cancer and Hypoactive Sexual Desire Disorder	To compare the disease free survival rate of patients taking aromatase inhibitor (+/- ovarian suppression therapy) to those taking aromatase inhibitor therapy (+/- ovarian suppression therapy) plus bupropion. This is assessed by the time since treatment end to the date of disease progression, death, or least contact, whichever comes first	Until 3 years post-study enrollment
Overall survival in patients with early stage breast cancer and Hypoactive Sexual Desire Disorder	To compare the overall survival rate of patients taking aromatase inhibitor (+/- ovarian suppression therapy) to those taking aromatase inhibitor therapy (+/- ovarian suppression therapy) plus bupropion. This is defined as the time of treatment randomization to death or last contact in study participants.	Until 3 years post-study enrollment
Safety and tolerability of study drugs in patients with early stage breast cancer and Hypoactive Sexual Desire Disorder	To determine the safety and tolerability of aromatase inhibitor (+/- ovarian suppression therapy) versus aromatase inhibitor (+/- ovarian suppression therapy) and bupropion as defined by the number of adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.	Until 6 months post-study enrollment
Medication adherence of study drugs in patients with early stage breast cancer and Hypoactive Sexual Desire Disorder	To determine the rate of medication adherence for patients taking aromatase inhibitor (+/- ovarian suppression therapy) versus aromatase inhibitor (+/- ovarian suppression therapy) and bupropion. This is defined as the number of medication diary entries and physician queries to treatment.	Until 3 years post-treatment start

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence and response to treatment of Hypoactive Sexual Desire Disorder in patients with early stage breast cancer across different racial groups	Prevalence of Hypoactive Sexual Desire Disorder among different racial groups will be assessed by the number of of early breast cancer patients with HSDD who are African-American, Caucasian, and Hispanic while the response to treatment across racial groups will be calculated by the overall decrease in FSFI score for the groups.	Until 3 years post-treatment start

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Oana Danciu, MD, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2031

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Sexual Dysfunctions, Psychological; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Pharmacologic Actions; Chemical Actions and Uses; Nitriles; Triazoles; Ketones; Propiophenones; Letrozole; Anastrozole; Leuprolide; Goserelin; Bupropion; Aromatase Inhibitors; Gonadotropin-Releasing Hormone; exemestane
• Other Study ID Numbers: 2025-1138

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No