Breast Cancer, Infertility, Menopausal Symptoms
Conditions
Keywords
infertility, menopausal symptoms, stage II breast cancer, stage IIIA breast cancer, stage IA breast cancer, stage IB breast cancer, estrogen receptor-negative breast cancer, progesterone receptor-negative breast cancer
Brief summary
RATIONALE: Goserelin blocks hormone production in the ovaries. It is not yet known whether ovarian suppression using goserelin will prevent ovarian failure (early menopause) in women receiving chemotherapy for breast cancer. PURPOSE: This randomized phase III trial is studying how well giving goserelin together with chemotherapy works compared with chemotherapy alone in preventing early menopause in women with stage I, stage II, or stage IIIA breast cancer.
Detailed description
OBJECTIVES: Primary * Compare the rate of premature ovarian failure in women with stage I-IIIA hormone receptor-negative breast cancer treated with chemotherapy with vs without goserelin. Secondary * Compare the rate of ovarian dysfunction in patients treated with these regimens. * Compare ovarian reserve in patients treated with these regimens. * Describe the pregnancy rates in patients treated with these regimens. OUTLINE: This is a randomized study. Patients are stratified according to age (under 40 vs 40 to 49) and planned chemotherapy regimen (3- to 4-month/course anthracycline-based vs 6- to 8-month/course anthracycline-based vs 3- to 4-month/course non-anthracycline-based vs 6- to 8-month/course non-anthracycline-based). Patients are randomized to 1 of 2 treatment arms. * Arm 1: Patients receive cyclophosphamide-containing chemotherapy alone. Patients are followed at 1, 2, and 5 years. * Arm 2: Patients receive goserelin subcutaneously once every 4 weeks beginning 1 week before start of cyclophosphamide-containing chemotherapy. Treatment continues until completion of chemotherapy in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 416 patients (208 per treatment arm) will be accrued for this study within 3 years.
Interventions
DRUGcyclophosphamide
Part of planned chemotherapy regimen
DRUGgoserelin acetate
Given subcutaneously
Sponsors
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
ETOP IBCSG Partners Foundation
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed invasive breast cancer * Stage I-IIIA * Operable disease * Bilateral synchronous invasive breast cancer allowed provided primary tumors were diagnosed no more than 1 month apart and both tumors are hormone receptor negative * Must be planning to receive 3-8 months of a preoperative or postoperative chemotherapy regimen containing alkylating agents (anthracyclines or non-anthracyclines), meeting 1 of the following criteria: * 3-month/4-course anthracycline-based regimen * 6- to 8-month/course anthracycline-based regimen * 6- to 8-month/course non-anthracycline-based regimen * Hormone receptor status: * Estrogen receptor negative * Progesterone receptor negative PATIENT CHARACTERISTICS: Age * 18 to 49 Sex * Female Menopausal status * Premenopausal Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Other * Not pregnant or nursing * Fertile patients must use effective barrier contraception * No other prior malignancy except adequately treated basal cell or squamous cell skin cancer or any in situ cancer from which the patient has been disease-free for at least 5 years after treatment with curative intent PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * See Disease Characteristics * No prior cytotoxic chemotherapy Endocrine therapy * No other concurrent hormonal therapy Radiotherapy * Concurrent radiotherapy to the breast, chest wall, or lymph nodes allowed Surgery * See Disease Characteristics Other * Concurrent participation in other therapeutic clinical trials, including SWOG-S0221, allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Premature Ovarian Failure at 2 Years | 2 years | Ovarian failure at two years is defined as amenorrhea (absence of menstrual bleeding) for the preceding six months AND the presence of follicle-stimulating hormone (FSH) in the post-menopausal range. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Ovarian Dysfunction at 2 Years | 2 years | Ovarian dysfunction is defined as amenorrhea for the preceding three months and the presence of FSH, estradiol and/or inhibin B levels in the postmenopausal range. |
| Rate of Ovarian Dysfunction at 1 Year | 1 year | Ovarian dysfunction is defined as amenorrhea for the preceding three months and the presence of FSH, estradiol and/or inhibin B levels in the postmenopausal range. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ovarian Reserve at 1 and 2 Years | 1 and 2 years | Measurements of ovarian reserve will consist of Day 2 - 4 levels of FSH, estradiol and inhibin B during Month 12/13 and Month 24/25 (or if amenorrheic, anytime during Month 12/13 and Month 24/25). |
Countries
Australia, Belgium, Hungary, Italy, New Zealand, Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Patients receive cyclophosphamide-containing chemotherapy alone.
cyclophosphamide: Part of planned chemotherapy regimen | 113 |
| Arm 2 Patients receive goserelin subcutaneously once every 4 weeks beginning 1 week before start of cyclophosphamide-containing chemotherapy. Treatment continues until completion of chemotherapy in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Part of planned chemotherapy regimen
goserelin acetate: Given subcutaneously | 105 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 11 | 3 |
| Overall Study | Ineligible | 11 | 13 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Missing primary outcome data | 30 | 34 |
| Overall Study | Not evaluable: hysterectomy/oophorectomy | 2 | 4 |
| Overall Study | Not evaluable: withdrew consent | 5 | 4 |
Baseline characteristics
| Characteristic | Arm 1 | Arm 2 | Total |
|---|---|---|---|
| Age, Continuous | 38.7 years | 37.6 years | 37.7 years |
| Sex: Female, Male Female | 113 Participants | 105 Participants | 218 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 111 | 73 / 103 |
| serious Total, serious adverse events | 0 / 111 | 1 / 103 |
Outcome results
Primary
Rate of Premature Ovarian Failure at 2 Years
Ovarian failure at two years is defined as amenorrhea (absence of menstrual bleeding) for the preceding six months AND the presence of follicle-stimulating hormone (FSH) in the post-menopausal range.
Time frame: 2 years
Population: Patients who completed the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Chemotherapy | Rate of Premature Ovarian Failure at 2 Years | 15 Participants |
| Chemotherapy Plus Goserelin | Rate of Premature Ovarian Failure at 2 Years | 5 Participants |
Secondary
Rate of Ovarian Dysfunction at 1 Year
Ovarian dysfunction is defined as amenorrhea for the preceding three months and the presence of FSH, estradiol and/or inhibin B levels in the postmenopausal range.
Time frame: 1 year
Population: Patients with both menstrual status data and at least two available laboratory values (FSH, inhibin B, or estradiol levels) at year 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Chemotherapy | Rate of Ovarian Dysfunction at 1 Year | 28 Participants |
| Chemotherapy Plus Goserelin | Rate of Ovarian Dysfunction at 1 Year | 18 Participants |
Secondary
Rate of Ovarian Dysfunction at 2 Years
Ovarian dysfunction is defined as amenorrhea for the preceding three months and the presence of FSH, estradiol and/or inhibin B levels in the postmenopausal range.
Time frame: 2 years
Population: Patients with both menstrual status data and at least two available laboratory values (FSH, inhibin B, or estradiol levels) at year 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Chemotherapy | Rate of Ovarian Dysfunction at 2 Years | 22 Participants |
| Chemotherapy Plus Goserelin | Rate of Ovarian Dysfunction at 2 Years | 9 Participants |
Other Pre-specified
Ovarian Reserve at 1 and 2 Years
Measurements of ovarian reserve will consist of Day 2 - 4 levels of FSH, estradiol and inhibin B during Month 12/13 and Month 24/25 (or if amenorrheic, anytime during Month 12/13 and Month 24/25).
Time frame: 1 and 2 years