Title
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

Description
Younger age at diagnosis is an adverse prognostic factor in early breast cancer: women who are less than 35 years of age at diagnosis are more likely to die from their disease than their older counterparts following standard treatments. There remains a pressing need for advancements in therapeutic options for this patient population. One increasingly utilized option is ovarian suppression, which was first reported as treatment for advanced breast cancer in 1896 and has been examined in a multitude of clinical trials over the past century. As chemotherapeutic options became more commonplace for breast cancer therapy, however, the role of ovarian suppression became uncertain.

In the pre-genomic era, several studies evaluated the role of ovarian suppression compared to chemotherapy, with conflicting results. These studies either looked at ovarian suppression alone or at tamoxifen compared to chemotherapy. A meta-analysis examining LHRH-agonists (luteinizing hormone-releasing hormone) in the Early Breast Cancer Overview group (LHRH-agonists in Early Breast Cancer Overview group 2007) showed that when LHRH-agonists were added to tamoxifen, chemotherapy, or both, there was a 12.7% reduction in the risk of recurrence and a 15.1% reduction in the risk of death. When compared to chemotherapy, LHRH-agonists appeared to be equally as effective, especially if patients were less than 40 years of age. These older studies, conducted in the pre-taxane/anthracycline era, typically used CMF (cyclophosphamide, methotrexate, and fluorouracil) chemotherapy, and were designed prior to the use of genomic assays .

Objective
Primary Objective:
1. To 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).

Secondary Objectives:
1.To determine whether ACT added to OFS plus ET is superior to OFS plus ET in improving invasive disease-free survival (IDFS) among premenopausal, EBC patients with ER-positive, HER2-negative tumors and 21-gene RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).

2. To determine whether ACT added to OFS plus ET is superior to OFS plus ET in improving overall survival (OS) among premenopausal, EBC patients with ER-positive, HER2-negative tumors and 21-gene RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).

3. To determine whether ACT added to OFS plus ET is superior to OFS plus ET in improving distant recurrence-free interval (DRFI) among premenopausal, EBC patients with ER-positive, HER2-negative tumors and 21-gene RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).

4. To determine whether ACT added to OFS plus ET is superior to OFS plus ET in improving breast cancer-free interval (BCFI) among premenopausal, EBC patients with ER-positive, HER2-negative tumors and 21-gene RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).

5. To determine whether patients who receive ACT added to OFS plus ET will have more severe menopausal symptoms, measured by the FACT ESS-19 score, compared to those who do not receive ACT.

6. To determine whether patients who receive ACT added to OFS plus ET will have increased pain during aromatase inhibitor (AI) therapy compared to patients who do not receive ACT.

Treatment Active Comparator: Arm 1: Ovarian Function Suppression + Aromatase Inhibitor
Drug: Ovarian Function Suppression + Aromatase Inhibitor

Active Comparator: Arm 2 Adjuvant Chemotherapy + Ovarian Function Suppression + Aromatase Inhibitor
Drug: Ovarian Function Suppression + Aromatase Inhibitor
Drug: Adjuvant Chemotherapy + Ovarian Function Suppression

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Breast

Participating Institutions
Johnson Creek, UW Cancer Center; Mercy Health Systems, Janesville ; UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital