This Phase III Trial 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).
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 .
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3,960
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.
Adjuvant chemotherapy of investigator's choice followed by an aromatase inhibitor (AI) co-administered with an 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.
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
ACTIVE_NOT_RECRUITINGAnchorage Associates in Radiation Medicine
Anchorage, Alaska, United States
RECRUITINGAnchorage Radiation Therapy Center
Anchorage, Alaska, United States
SUSPENDEDAlaska Breast Care and Surgery LLC
Anchorage, Alaska, United States
Invasive breast cancer-free survival (IBCFS)
Time from randomization to the first diagnosis of local invasive recurrence following mastectomy, local invasive recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause prior to recurrence or contralateral breast cancer.
Time frame: Time from randomization for duration of trial, 11 years
Invasive disease-free survival (IDFS)
Time from randomization to the first diagnosis of local invasive recurrence following mastectomy, local invasive recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral invasive breast cancer, second non-breast primary cancer (excluding squamous or basal cell carcinoma of the skin), or death from any cause prior to recurrence or second primary cancer.
Time frame: Time from randomization for duration of trial, 11 years
Overall survival
Time from randomization to death from any cause
Time frame: Time from randomization for duration of trial, 11 years
Distant recurrence-free interval (DRFI)
Time from randomization until the first diagnosis of distant metastasis or death from breast cancer, regardless of occurrence of any intervening local or regional recurrences, contralateral breast cancers, or non-breast second primary cancers. This endpoint is censored at the time of death from causes other than breast cancer.
Time frame: Time from randomization for duration of trial, 11 years
Breast cancer-free interval (BCFI)
Time from randomization until the first diagnosis of local invasive recurrence, regional recurrence, distant recurrence, contralateral breast cancer or death from breast cancer.
Time frame: Time from randomization for duration of trial, 11 years
Menopausal symptoms measured by the FACT ESS-19 score
The FACT-ES 19 Item Endocrine Symptom Subscale (ESS-19) score. The score is calculated as a sum of 19 endocrine symptom items. The score range is 0-76 and a higher score indicates better QOL.
Time frame: Measured at one year after randomization
Pain during aromatase inhibitor (AI) therapy
The pain severity question from the PROMIS-29 Profile. Pain will be measured on a 0-10 scale using the pain questions from the PROMIS-29 profile.
Time frame: Measured at one year after randomization
Norman Wolmark, MD
CONTACT
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Alaska Oncology and Hematology LLC
Anchorage, Alaska, United States
RECRUITINGAlaska Women's Cancer Care
Anchorage, Alaska, United States
RECRUITINGAnchorage Oncology Centre
Anchorage, Alaska, United States
SUSPENDEDKatmai Oncology Group
Anchorage, Alaska, United States
RECRUITINGProvidence Alaska Medical Center
Anchorage, Alaska, United States
RECRUITINGKingman Regional Medical Center
Kingman, Arizona, United States
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