Leuprolide and Goserelin for Ovarian Function Suppression in Pre- or Peri-menopausal Women With Breast Cancer, OFS Trial

13MAY2026- New Amendment approved which made the following changes:

* Study title updated reflect updated trial design
* Arms updated to reflect study drug dosing assignments
* Eligibility Criteria

• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo blood sample collection
• Electronic Health Record Review (Other): Ancillary studies
• Goserelin (Drug), also known as ICI-118630: Given SC
• Leuprolide (Drug), also known as Leuprorelin: Given IM
• Questionnaire Administration (Other): Ancillary studies

Primary outcomes

• Proportion of participants with ultrasensitive estradiol concentration > 10 pg/ml [During the first 24 weeks of therapy]: Analyses will primarily be descriptive reporting the overall and by treatment group proportions of women with ultrasensitive estradiol concentration and the corresponding exact binomial 95% confidence intervals over the first 24 weeks of gonadotropin releasing hormone agonist (GnRHa) therapy.

Secondary outcomes

• Proportion of participants with ultrasensitive estradiol concentration > 10 pg/ml [At 4 weeks after initial GnRHa treatment administration]: Will be described with corresponding 95% confidence intervals overall and by treatment group.
• Proportion of participants with ultrasensitive estradiol concentration > 10 pg/ml [Any time after 4 weeks of initial GnRHa treatment administration, assessed cycle 3 day 1-cycle 7 day 1 (cycle length = 28 days)]: Will be described with corresponding 95% confidence intervals overall and by treatment group.
• Change in Functional Assessment of Cancer Therapy-(FACT)-Endocrine Subscale (ES) Trial Outcome Index [Up to 24 weeks]: Will use linear mixed-effects models with fixed effects for study group, time, and their interaction. For each outcome, a random intercept for each participant will be included to account for within-subject correlation. This approach allows for estimation of longitudinal trends in FACT-ES scores and assessment of whether changes over time differ between treatment arms. Missing data will be handled using maximum likelihood estimation under the assumption of missing at random (MAR).
• Change in FACT-ES Endocrine Symptom Subscale [Up to 24 weeks]: Will use linear mixed-effects models with fixed effects for study group, time, and their interaction. For each outcome, a random intercept for each participant will be included to account for within-subject correlation. This approach allows for estimation of longitudinal trends in FACT-ES scores and assessment of whether changes over time differ between treatment arms. Missing data will be handled using maximum likelihood estimation under the assumption of MAR.
• Percentage of participants reporting discomfort of 6/10 or higher on the Discomfort of Injection questionnaire [At the day following initial GnRHa injection]: Will be described by study arm and with corresponding exact binomial 95% confidence intervals.
• Percentage of participants reporting discomfort of 6/10 or higher on the Discomfort of Injection questionnaire [Before administration of the second GnRHa injection]: Will be described by study arm and with corresponding exact binomial 95% confidence intervals.
• Receipt of GnRHa therapy within ± 1 day of planned dosing [Up to 24 weeks]: Planned dosing should be given every 28 days. The proportion of patients who receive GnRHa therapy within ± 1 day of planned dosing will be reported overall and by study arm with corresponding exact binomial 95% confidence intervals.
• Incidence of adverse events (AEs) [Up to 24 weeks]: AEs will be graded and described using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be reported using descriptive statistics for each GnRHa study arm.

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Female subject aged ≥ 18 years
* Pre- or peri-menopausal patient, who had (1) menses either within the 12 months prior to or since breast cancer diagnosis or (2) estradiol concentration above the postmenopausal range per institutional laboratory guidance either within the 12 months prior to or since breast cancer diagnosis.
* Planning to take GnRHa therapy in combination with oral endocrine therapy (tamoxifen, anastrozole, exemestane, or letrozole) for adjuvant treatment of stage 1-3 breast cancer or for treatment of metastatic breast cancer. Prior treatment with GnRHa therapy for treatment of non-oncologic conditions or during chemotherapy is permitted.
* Not planning bilateral salpingo-oophorectomy during the 6-month study duration
* Completion of chemotherapy, if given. Concurrent use of trastuzumab, pertuzumab, bisphosphonate therapy, poly adenosine diphosphate-ribose polymerase (PARP) inhibitor therapy, cyclin D kinase 4/6 (CDK4/6) inhibitor, and/or phosphoinositide 3-kinase (PI3K) inhibitor therapy is permitted
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

Exclusion Criteria:

* Prior bilateral salpingo-oophorectomy
* Known to be pregnant or breastfeeding (negative pregnancy test will be confirmed prior to study treatment initiation)
* Concomitant use of systemic or transdermal estrogen products
* Known allergy or hypersensitivity to goserelin or leuprolide, or any of the excipients in the medications
* Unable to take oral medications
* Any medical condition that would interfere with the absorption of endocrine therapy. Prior gastric bypass is permitted
* Patients with a prior or concurrent malignancy whose natural history or treatment, in the opinion of the treating investigator, has the potential to interfere with the safety or efficacy assessment of the investigational regimen

• Norah L Henry, Principal investigator, University of Michigan Rogel Cancer Center