Stage I~III Breast Cancer Stage I Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer, OFSET, BR009
Conditions
Interventions
Eligible patients will be randomized 1:1 to ovarian suppression plus endocrine therapy (Arm 1) versus adjuvant chemotherapy added to ovarian suppression plus endocrine therapy (Arm 2).
Stratification
no), and age (18-39 vs 40 and older).
Arm 1:
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 dosin
Sponsors
Matsumoto Koji
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. The patient or a legally 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 information. 2. Female patients must be greater than or equal to 18 years of age. 3. 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. 4. The patient must have an ECOG performance status of less than or equal to 2 (or Karnofsky greater than or equal to 60%). 5. Patients may 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. 6. Patients may 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. 7. Patient may have undergone a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy. 8. For patients who undergo a lumpectomy, the margins of the resected specimen or reexcision must be histologically free of invasive tumor and DCIS 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 are eligible without additional resection.) 9. 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.) 10. Patient must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND). 11. 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. 12. Oncotype DX RS 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: low histologic grade with primary tumor size > 3 cm, intermediate histologic grade with primary tumor size > 2 cm, or high histologic grade with primary tumor size > 1 cm. - If 1-3 nodes involved: - Oncotype DX RS must be < 26. *Patients with a ""Low Risk"" or ""MP1"" MammaPrint result must have eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3
Exclusion criteria
Exclusion criteria: 1. Definitive clinical or radiologic evidence of metastatic disease. 2. pT4 tumors, including inflammatory breast cancer. 3. History of ipsilateral or contralateral invasive breast cancer. (Patients with synchronous and/or previous DCIS or LCIS are eligible.) - If prior ipsilateral DCIS was treated with lumpectomy and XRT, a mastectomy must have been performed for the current cancer. 4. Life expectancy of ULN for the lab or > 1.5 x ULN for patients who have a bilirubin elevation due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; - AST(SGOT)/ALT(SGPT): > 3 x institutional ULN; - Renal function of GFR < 30 mL/min/1.73m2. 6. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. 7. Non-epithelial breast malignancies such as sarcoma or lymphoma. 8. Any treatment with radiation therapy, chemotherapy, or biotherapy administered for thecurrently diagnosed breast cancer prior to pre-entry. (Patients with prior ET of more than 6 weeks duration for treatment of this cancer are not eligible.) Prior tamoxifen given for breast cancer prevention is allowed. Prior aromatase inhibitor (AI) or GnRH for fertility preservation is allowed. 9. Hormonally based contraceptive measures must be discontinued prior to pre-entry (including progestin/progesterone IUDs). 10. Patients with evidence of chronic hepatitis B virus (HBV) infection are ineligible unless the HBV viral load is undetectable on suppressive therapy. Patients with a history of hepatitis C virus (HCV) infection are ineligible unless they have been treated and cured or have an undetectable HCV viral load if still on active therapy. 11. Pregnancy or lactation at the time of pre-entry. (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to pre-entry.) 12. Other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is invasive breast cancer-free survival (IBCFS), defined as 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Invasive disease-free survival (IDFS), defined as 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. - Overall survival (OS), defined as time from randomization to death from any cause. - Distant recurrence-free interval (DRFI), defined as 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. - Breast cancer-free interval (BCFI), defined as time from randomization until the first diagnosis of local invasive recurrence, regional recurrence, distant recurrence, contralateral breast cancer, or death from breast cancer. - Frequencies of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0). - The FACT-ES Endocrine Symptoms Subscale score ESS-19 measured at one year after randomization. - The pain severity score from the PROMIS-29 Profile measured at one year after randomization. | — |
Countries
Canada, Colombia, Japan, Mexico, Peru, Uruguay, USA
Contacts
Public ContactKoji Matsumoto
Hyogo Cancer Center
Outcome results
None listed