Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Alternate Title

Chemotherapy and Hormone Therapy in Treating Premenopausal or Perimenopausal Women With Node-Negative Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	pre/perimenopausal		IBCSG-VIII NCI-F90-0001

Objectives

I.  Compare relapse rates and survival of node-negative pre- and 
perimenopausal breast cancer patients randomly assigned to 6 courses of 
cyclophosphamide/methotrexate/fluorouracil (CMF) followed by 72 weeks of 
goserelin vs. CMF alone vs. 96 weeks of goserelin alone.

II.  Evaluate patients' perceptions of well being and coping during adjuvant 
treatment, following treatment but before relapse, and after relapse.

Entry Criteria

Disease Characteristics:

Stage T1-3, pN0, M0 breast cancer

Potentially curatively resected within 6 weeks of entry by one of the
following:
  Total mastectomy

  Breast-conserving procedure (lumpectomy or quadrantectomy) for tumors less
  than 5 cm
     Total mastectomy within 4 weeks of initial surgery required if margins
     positive after initial surgery

Axillary clearance (not sampling) required at surgery, with no evidence of
nodal involvement upon examination of at least 8 lymph nodes from ipsilateral
axilla

Suspicious manifestations of metastatic disease (e.g., hot spots on bone scan)
must be proven benign

No bilateral breast cancer

Masses in contralateral breast must be biopsy-proven to be benign

Hormone receptor status:
  Estrogen receptor positive

Prior/Concurrent Therapy:

Biologic therapy:
  No prior biologic therapy for breast cancer

Chemotherapy:
  No prior chemotherapy for breast cancer

Endocrine therapy:
  No prior hormonal therapy for breast cancer

Radiotherapy:
  No prior radiotherapy for breast cancer
  Concurrent radiotherapy allowed for patients with less than total mastectomy

Surgery:
  Potentially curative surgery within 6 weeks of entry required

Patient Characteristics:

Age:
  See Menopausal status

Sex:
  Female

Menopausal status:
  Pre- or perimenopausal, i.e.:
     Age greater than 52 with last normal menstrual period within 1 year
     Age 52 or younger with last normal menstrual period within 3 years or
        currently menstruating
     Age 55 or younger with hysterectomy that left one functioning ovary
     Biochemically confirmed ovarian function in questionable cases

Performance status:
  Not specified

Hematopoietic:
  WBC at least 4,000/mm3
  Platelet count at least 100,000/mm3

Hepatic:
  Bilirubin less than 1.1 mg/dL (20 micromoles/L)
  AST less than 60 IU/L

Renal:
  Creatinine less than 1.3 mg/dL (120 micromoles/L)

Other:
  No nonmalignant systemic disease that would preclude protocol therapy
   (including lipid metabolism disorders)
  No psychiatric or addictive disorder that would preclude informed consent
  No second malignancy except:
   Nonmelanomatous skin cancer
   Adequately treated in situ carcinoma of the cervix
  Not pregnant or nursing (including those who have stopped nursing
   within the past 6 months)

Expected Enrollment

1,065 evaluable patients will be studied over about 5 years.

Outline

This is a randomized study.  Patients are stratified by participating 
institution.  Patients with breast conserving surgery are further stratified 
by whether radiotherapy is planned.

Patients in arm I, which closed in March of 1992, were observed without 
treatment.

Patients in arm II receive goserelin every 28 days for 2 years.

Patients in arm III receive cyclophosphamide, methotrexate, and fluorouracil 
(CMF) every 28 days for 6 courses.

Patients in arm IV receive CMF as above, followed by goserelin every 28 days 
for 18 months.

Patients who have undergone breast conserving surgery may receive optional 
radiation therapy, beginning within 3 months of entry for the first and second 
arms and 2 weeks following the last course of CMF for the third and fourth 
arms.

All patients are followed every 3 months for 1 year, then every 6 months for 2 
years, then annually thereafter.

Viale G, Regan MM, Maiorano E, et al.: Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: predictive value of centrally reviewed expression of estrogen and progesterone receptors--International Breast Cancer Study Group. J Clin Oncol 26 (9): 1404-10, 2008.[PUBMED Abstract]

Bernhard J, Zahrieh D, Castiglione-Gertsch M, et al.: Adjuvant chemotherapy followed by goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and quality of life in premenopausal patients--the International Breast Cancer Study Group Trial VIII. J Clin Oncol 25 (3): 263-70, 2007.[PUBMED Abstract]

Castiglione-Gertsch M, O'Neill A, Price KN, et al.: Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst 95 (24): 1833-46, 2003.[PUBMED Abstract]

Castiglione-Gertsch M, O'Neill A, Gelber RD, et al.: Is the addition of adjuvant chemotherapy always necessary in node negative (N-) pre/perimenopausal breast cancer patients (pts) who receive goserelin? First results of IBCSG trial VIII. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-149, 2002.

Maiorano E, Regan MM, Viale G, et al.: Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer: Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy. Breast Cancer Res Treat : , 2009.[PUBMED Abstract]

Pestalozzi BC, Zahrieh D, Mallon E, et al.: Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials. J Clin Oncol 26 (18): 3006-14, 2008.[PUBMED Abstract]

Ravaioli A, Monti F, Regan MM, et al.: p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer. Ann Oncol 19 (4): 660-8, 2008.[PUBMED Abstract]

Viale G, Regan MM, Mastropasqua MG, et al.: Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst 100 (3): 207-12, 2008.[PUBMED Abstract]

Karlsson P, Cole BF, Price KN, et al.: The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer. J Clin Oncol 25 (15): 2019-26, 2007.[PUBMED Abstract]

Keshaviah A, Dellapasqua S, Rotmensz N, et al.: CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. Ann Oncol 18 (4): 701-8, 2007.[PUBMED Abstract]

Cuzick J, Ambroisine L, Davidson N, et al.: Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet 369 (9574): 1711-23, 2007.[PUBMED Abstract]

Pestalozzi BC, Zahrieh D, Price KN, et al.: Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol 17 (6): 935-44, 2006.[PUBMED Abstract]

Regan MM, Viale G, Mastropasqua MG, et al.: Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J Natl Cancer Inst 98 (21): 1571-81, 2006.[PUBMED Abstract]

Szwarc SE, Bonetti M: Modelling menstrual status during and after adjuvant treatment for breast cancer. Stat Med 25 (20): 3534-47, 2006.[PUBMED Abstract]

Aebi S, Castiglione-Gertsch M: Adjuvant endocrine therapy for the very young patients. Breast 12 (6): 509-15, 2003.[PUBMED Abstract]

Castiglione-Gertsch MM: Chemoendocrine therapy for node-negative breast cancer: International Breast Cancer Study Group (IBCSG) trials VIII and IX. [Abstract] Breast Cancer Res Treat 76 (Suppl 1): A-11, 2002.

Kaufmann M: Luteinizing hormone-releasing hormone analogues in early breast cancer: updated status of ongoing clinical trials. Br J Cancer 78 (Suppl 4): 9-11, 1998.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

International Breast Cancer Study Group

Monica Castiglione-Gertsch, MD, Protocol chair		Ph: 41-31-389-9391 Email: monica.castiglione@ibcsg.org