Breast Cancer
Conditions
Keywords
stage IIIA breast cancer, stage I breast cancer, stage II breast cancer
Brief summary
The PERCHE trial evaluated the worth of adding adjuvant chemotherapy for premenopausal women with steroid hormone receptor positive early invasive breast cancer who receive ovarian function suppression plus either tamoxifen or exemestane for five years. The use of chemotherapy was determined by randomization. The method of ovarian function suppression (GnRH analogue for five years, surgical oophorectomy or ovarian irradiation) and the choice of tamoxifen or exemestane were determined by the investigator or by randomization in the IBCSG 25-02 TEXT trial \[recommended option\]. The trial was terminated early due to poor accrual.
Detailed description
OBJECTIVES: * Compare ovarian function suppression and tamoxifen or exemestane with vs without adjuvant chemotherapy in premenopausal women with endocrine-responsive resected breast cancer. * Compare the disease-free and overall survival of patients treated with these regimens. * Compare sites of first treatment failure in patients treated with these regimens. * Compare the incidence of second nonbreast malignancies in patients treated with these regimens. * Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens. PLANNED OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more), method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation), chemotherapy if randomized to arm II (not containing vs containing an anthracycline or taxane), and endocrine agent (tamoxifen vs exemestane vs selected by subsequent randomization in the TEXT trial). Treatment duration is five years. Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 4 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. NOTE: Trial was terminated early due to poor accrual.
Interventions
DRUGchemotherapy
Planned duration of chemotherapy: 2 months if an anthracycline is included (e.g., 4 cycles of EC or AC) or 4 months if no anthracycline is given (e.g., 6 cycles of CMF) is recommended. Unless medically contraindicated, an anthracycline-containing regimen using epirubicin should be given.
DRUGexemestane
Exemestane 25 mg orally daily for until 5 years from date of randomization, unless relapse or intolerance should occur earlier.
DRUGtamoxifen
Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.
DRUGtriptorelin
Triptorelin (GnRH analogue) 3.75 mg by intramuscular injection every 28 days for 5 years from randomization, unless relapse or intolerance should occur earlier or surgical oophorectomy or ovarian irradiation is subsequently performed.
PROCEDUREoophorectomy
Bilateral surgical oophorectomy via laparotomy or laparoscopy.
PROCEDUREovarian irradiation
Bilateral ovarian irradiation.
Sponsors
National Cancer Institute (NCI)
Breast International Group
ETOP IBCSG Partners Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed breast cancer confined to the breast and axillary nodes * No distant metastatic disease * Tumor detected in the internal mammary chain by sentinel node procedure allowed * Must have undergone 1 of the following procedures for primary breast cancer within the past 12 weeks and have no known clinical residual locoregional disease: * Total mastectomy with or without adjuvant radiotherapy * Breast-conserving surgery (e.g., lumpectomy, quadrantectomy, or partial mastectomy with margins clear\* of invasive cancer and ductal carcinoma in situ) followed by radiotherapy NOTE: \*If all other margins are clear, a positive posterior (deep) margin is permitted, provided the excision was performed down to the pectoral fascia and all tumor has been removed OR a positive anterior (superficial; abutting skin) margin is allowed provided all tumor was removed * Prior axillary lymph node dissection or negative axillary sentinel node biopsy required * Patients with microscopically positive axillary sentinel nodes allowed provided they were evaluated on a clinical trial evaluating microscopically positive lymph nodes * No locally advanced, inoperable breast cancer, including any of the following characteristics: * Inflammatory breast cancer * Supraclavicular node involvement * Enlarged internal mammary nodes (unless pathologically negative) * No prior ipsilateral or contralateral invasive breast cancer * Histologically diagnosed synchronous bilateral invasive breast cancer within the past 2 months allowed if the bilateral disease meets all other eligibility criteria * Hormone receptor status: * Estrogen receptor and/or progesterone receptor positive in each tumor * At least 10% of tumor cells positive by immunohistochemistry PATIENT CHARACTERISTICS: Age * Premenopausal Sex * Female Menopausal status * Premenopausal * Estradiol in the premenopausal range after surgery Performance status * Not specified Life expectancy * Not specified Hematopoietic * Not specified Hepatic * No systemic hepatic disease that would preclude prolonged follow-up Renal * No systemic renal disease that would preclude prolonged follow-up Cardiovascular * No prior deep venous thrombosis and/or embolism unless patient is medically suitable * No systemic cardiovascular disease that would preclude prolonged follow-up Pulmonary * No systemic pulmonary disease that would preclude prolonged follow-up Other * Not pregnant or nursing * Fertile patients must use effective nonhormonal contraception * No other prior or concurrent invasive malignancy except adequately treated basal cell or squamous cell skin cancer, nonbreast carcinoma in situ without invasion, contralateral or ipsilateral carcinoma in situ of the breast * No prior or concurrent nonbreast invasive malignancy within the past 5 years that is nonrecurrent including any of the following: * Stage I papillary thyroid cancer * Stage Ia carcinoma of the cervix * Stage Ia or b endometrioid endometrial cancer * Borderline or stage I ovarian cancer * No other nonmalignant systemic disease that would preclude prolonged follow-up * No history of noncompliance with medical regimens * No psychiatric, addictive, or other disorder that would preclude study compliance or giving informed consent PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior neoadjuvant or adjuvant chemotherapy * Neoadjuvant or adjuvant trastuzumab (Herceptin®) allowed Endocrine therapy * No prior neoadjuvant or adjuvant endocrine therapy after breast cancer diagnosis * No prior tamoxifen or other selective estrogen-receptor modulator (e.g., raloxifene) within 1 year before the breast cancer diagnosis * No other concurrent oral or transdermal hormonal therapy, including any of the following: * Estrogen * Progesterone * Androgens * Aromatase inhibitors * Hormone replacement therapy * Oral or other hormonal contraceptives, including implant and depot injections * Raloxifene or other selective estrogen-receptor modulators Radiotherapy * See Disease Characteristics * No prior ovarian irradiation Surgery * See Disease Characteristics * No prior bilateral oophorectomy Other * No other prior neoadjuvant therapy * No other concurrent investigational agents * No concurrent bisphosphonates unless bone density has been documented at least 1.5 standard deviations below the young adult normal mean or the patient is participating in a randomized clinical trial setting testing bisphosphonates in the adjuvant breast cancer setting
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-free Survival | For first time at a median follow up approximately 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival | For first time at a median follow up approximately 5 years |
| Systemic Disease-free Survival | For first time at a median follow up approximately 5 years |
| Sites of First Treatment Failure | For first time at a median follow up approximately 5 years |
Countries
Hungary, Italy, Switzerland
Participant flow
Recruitment details
Enrollment opened 4Aug03; the first patient was randomized on 1Jun04. The accrual goal for the study was 1750 patients. A total of 29 patients were randomized as of 31Dec06 when the trial was terminated. 25 of these 29 patients were also enrolled in the TEXT trial (IBCSG 25-02).
Participants by arm
| Arm | Count |
|---|---|
| OFS Plus T or E for 5 Years Ovarian function suppression (OFS) by triptorelin for 5 years or surgical oophorectomy or ovarian irradiation PLUS tamoxifen (T) or exemestane (E) for 5 years. | 14 |
| Chemotherapy Plus OFS Plus T or E for 5 Years Chemotherapy plus ovarian function suppression (OFS) by triptorelin for 5 years or surgical oophorectomy or ovarian irradiation PLUS tamoxifen (T) or exemestane (E) for 5 years. | 15 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study was terminated early | 14 | 15 |
Baseline characteristics
| Characteristic | OFS Plus T or E for 5 Years | Chemotherapy Plus OFS Plus T or E for 5 Years | Total |
|---|---|---|---|
| Age, Continuous | 45 years | 45 years | 45 years |
| Sex: Female, Male Female | 14 Participants | 15 Participants | 29 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 | 0 / 14 | 0 / 15 |
| serious Total, serious adverse events | 0 / 14 | 6 / 15 |
Outcome results
Primary
Disease-free Survival
Time frame: For first time at a median follow up approximately 5 years
Population: The trial was terminated early due to poor accrual. No outcome measure data is available.
Secondary
Overall Survival
Time frame: For first time at a median follow up approximately 5 years
Population: The trial was terminated early due to poor accrual. No outcome measure data is available.
Secondary
Sites of First Treatment Failure
Time frame: For first time at a median follow up approximately 5 years
Population: The trial was terminated early due to poor accrual. No outcome measure data is available.
Secondary
Systemic Disease-free Survival
Time frame: For first time at a median follow up approximately 5 years
Population: The trial was terminated early due to poor accrual. No outcome measure data is available.