A Phase III Adjuvant Trial Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression plus Endocrine Therapy in Premenopausal Patients with pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score ≤ 25 (OFSET)

Study on Chemotherapy and Hormone Therapy for Breast Cancer

T
Tarah Ballinger, MD

Primary Investigator

Recruiting
18 years - 60 years
Female
Phase 3
16 participants needed
4 Locations

Brief description of study

This study will determine whether adjuvant chemotherapy (ACT) added to ovarian function suppression (OFS) plus endocrine therapy (ET) is superior to OFS plus ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early- stage breast cancer (EBC) patients with estrogen receptor (ER)-positive, HER2-negative tumors and 21-gene recurrence score (RS) between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

Aromatase inhibitor co-administered with a GnRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of GnRH agonist and dosing schedule is per investigator's discretion. Options commonly include goserelin, leuprolide, or triptorelin given monthly or every-three-months. The dose and schedule of AI should be consistent with the drug package insert. Endocrine treatment beyond 5 years is at the investigator's discretion. Bilateral oophorectomy may substitute for ovarian suppression if desired
 

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Breast Cancer
  • Age: 18 years - 60 years
  • Gender: Female

  • Inclusion Criteria: A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
    • Thegally authorized representative must provide study-specific informed consent prior to pre-entry and, for patients treated in the U.S., authorization permitting release of personal health.
    • Female patients must be greater than or equal to 18 years of age.
    • Patients must be premenopausal (evidence of functioning ovaries) at the time of pre-entry. For study purposes, premenopausal is defined as:
    • Age 50 years or under with spontaneous menses within 12 months; or
    • Age greater than 50-60 years with spontaneous menses within 12 months plus follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal range; or
    • Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and estradiol levels in the premenopausal range; or
    • Patients with prior hysterectomy must have FSH and estradiol levels in the premenopausal range.
    • The patient must have an ECOG performance status of less than or equal to 2 (or Karnofsky greater than or equal to 60%).
    • Patientsy have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
    • Patientsy have multicentric or multifocal breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
    • Patient may have undergone a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
    • Forwho undergo a lumpectomy, the margins of the resected specimenust be histologically free of invasive tumor and DCIS (ductal carcinoma in situ) with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. (Patients with margins positive for LCIS (lobular carcinoma in situ) aregible without additional resection.)
    • For patients who undergo mastectomy, the margins must be free of residual gross tumor. (Patients with microscopic positive margins are eligible if post-mastectomy RT (radiation therapy) of the chest wall will be administered.)
    • Patient must have undergone axillary staging withde biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
    • The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
    • By pathologic evaluation, primary tumor must be pT1-3. (If N0, must be T1c or higher.)
    • By pathologic evaluation, ipsilateral nodes must be pN0 or pN1 (pN1mi, pN1a, pN1b, pN1c).
    • Patients with positive isolated tumor cells (ITCs) in axillary nodes will be considered N0 for eligibility purposes.
    • Patients with micrometastatic nodal involvement (0.2-2 mm) will be considered N1.
    • Oncotype DX RS (recurrence score) requirements*:
    • If node-negative:
    • Oncotype DX RS must be RS 21-25, or
    • Oncotype DX RS must be 16-20 and disease must be high clinical risk, defined as:w histologic grade with primary tumor size greater than 3 cm, intermediate histologic grade with primary tumor size greater than 2 cm,high histologic grade with primary tumor size greater than 1 cm.
    • If 1-3 nodes involved:
    • Oncotype DX RS must be less than 26.
      * Patients with a "Low Risk" or "MP1" MammaPrint (a genomic test that analyzes the activity of certain genes in early-stage breast cancer) result must have eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3.1). Blocks or unstained slides must be sent to the Genomic Health centralized laboratory for testing at no cost to these patients. If MammaPrint High Risk or MP2, these patients are not eligible.
    • The tumor must be ER and/or PgR-positive (progesterone receptor) by current ASCO/CAP guidelines based on local testing results. Patients with greater than or equal to 1% ER and/or PgR staining by IHC will be classified as positive.
    • Theumor must be HER2-negative by current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines based on local testing results.
    • The interval between the last surgery for breast cancer (including re-excision of margins) and pre-entry must be no more than 16 weeks.
    • Short course of endocrine therapy of lesshan 6 weeks duration before pre-entry is acceptable either as neoadjuvant or adjuvant therapy. An Oncotype DX RS must be performed on core biopsy specimen obtained prior to initiation of neoadjuvant endocrine therapy if received.
    • Patients with a prior or concurrent non-breast malignancy whose natural history or treatment does not have the potential to interfere with the safety ory assessment of the investigational regimen are eligible for this trial. This would include prior cancers treated with curative intent.
    • HIV-infectedve anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
    • Radiation therapy should be used according to standard guidelines; the intended radiation therapy should be declared prior to pre-entry.

This study investigates whether adding chemotherapy to ovarian function suppression and hormone therapy improves breast cancer-free survival in premenopausal women. The focus is on those with early-stage breast cancer that is estrogen receptor-positive and HER2-negative. The study will compare outcomes between those receiving chemotherapy in addition to hormone treatments and those receiving only hormone treatments.

Participants will receive a hormone therapy called an aromatase inhibitor along with a GnRH agonist for five years. These medications help lower estrogen levels. The choice of specific drugs and their dosing schedule will be determined by the study doctor. Some participants may have surgery to remove their ovaries instead of taking the GnRH agonist. The study will observe how these treatments affect breast cancer progression.

  • Who can participate: Women who are 18 years or older, have functioning ovaries, and are premenopausal can join. They must have early-stage breast cancer that is estrogen receptor-positive and HER2-negative. Other specific criteria about cancer stage and treatment history apply.
  • Study details: Participants will take hormone therapy and may receive chemotherapy. The hormone therapy involves a GnRH agonist and an aromatase inhibitor. A placebo is not used in this study.
Updated on 23 Sep 2025. Study ID: CTO-NRG-BR009

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