None listed
Conditions
Brief summary
This trial involves premenopausal women who after surgery for their breast cancer are found to have tumours which are hormone receptor positive (stimulated by hormones) and who also have positive axillary lymph nodes (‘glands under the arm pit’ containing cancer). For these women it is not known whether hormonal treatment alone is sufficient, or whether the addition of chemotherapy may be beneficial in reducing the incidence of disease recurrence and improving survival. Women who take part in this trial will all have their ovarian function suppressed and receive Tamoxifen. In addition, patients may or may not receive chemotherapy.
Interventions
Arm A: Ovarian ablation and Tamoxifen (20mg orally daily) maintenance to 5 years
Arm B: Ovarian ablation + 4 cycles of Doxorubicin (60mg/m^2 iv) or epirubicin (90mg/m^2 iv) and cyclophosphamide (600mg/m^2 iv), followed by Tamoxifen (20mg orally daily) maintenance to 5 years.
Ovarian ablation can use any of the following methods:
* bilateral surgical oophorectomy via laparatomy or laparascopy OR
* bilateral ovarian irradiation OR
* GnRH (gonadotropin releasing hormone) analogue 3.6mg every 28 da
Arm A: Ovarian ablation and Tamoxifen (20mg orally daily) maintenance to 5 years Arm B: Ovarian ablation + 4 cycles of Doxorubicin (60mg/m^2 iv) or epirubicin (90mg/m^2 iv) and cyclophosphamide (600mg/m^2 iv), followed by Tamoxifen (20mg orally daily) maintenance to 5 years. Ovarian ablation can use any of the following methods: * bilateral surgical oophorectomy via laparatomy or laparascopy OR * bilateral ovarian irradiation OR * GnRH (gonadotropin releasing hormone) analogue 3.6mg every 28 days continued for 2 years or until the patient is 55 years old, whichever is longer. Note: ovarian ablation initiated with GnRH analogue may be continued by oophorectomy or radiation therapy. Chemotherapy (21 day cycles) should start immediately after the ovarian ablation procedure or at day 1 of GnRH(gonadotropin releasing hormone) analogue administration; within 6 weeks of primary surgery.
Sponsors
International Breast Cancer Study Group
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Premenopausal women with histologically proven primary breast cancer• Positive lymph nodes (metastases detected in 1 or more of at least 8 ipsilateral axillary nodes examined). The primary tumour must be classified as T1a,b,c T2 or T3, pN1, M0 (UICC 1987)• Patients must be judged suitable for treatment with endocrine therapy alone. As a minimum, must have ER positive tumours (ER>= 10 fmol/mg cytosol protein) or PR positive tumours (PgR>= 10 fmol/my cytosol protein)• Patients must have had:a) Either total mastectomy or, optionally if the tumour is <=5cm, breast-conserving procedure (lumpectomy or quadrantectomy)b) Axillary clearance with at least eight lymph nodes available for pathological examinationc) The primary breast cancer surgical procedure must be within 6 weeks prior to randomisation• Minimum of 8 lymph nodes histopathologically examined with at least one found positive• Tumour must be confined to breast without detected metastases• Adequate marrow function (WBC >= 4.0 x 10^9/L and platelet count >= 100 x 10^9/L)• Adequate renal function (serum creatinine < 120 umol/L) and hepatic function (serum bilirubin < 20umol/L, AST (SGOT) < 60 i.u./L)• Informed consent• Geographically accessible for follow-up
Exclusion criteria
• Patients without axillary node involvement• Malignant breast tumours other than carcinoma• T4 carcinoma with ulceration, infiltration of skin, peau d'orange or inflammatory breast cancer• Bilateral malignancies, or mass in opposite breast• Margins of resected specimen contained tumour cells• ER- and PR- tumours• Previous or concomitant other malignancy except basal or squamous cell carcinoma of skin or in situ carcinoma of cervix• Prior therapy for breast cancer• Non-malignant systemic diseases preventing treatment options or follow-up• Psychiatric or addictive disorders preventing informed consent• Bone scans showing hot spots which cannot be confirmed as benign disease• Pregnant or lactating
Outcome results
None listed