OBJECTIVES:

1. Estimate overall and relapse-free survival of women with
   early-stage breast cancer receiving adjuvant tamoxifen with
   or without adjuvant chemotherapy and/or ovarian
   suppression.

PARTICIPATION CRITERIA

• Pre-, peri- or postmenopausal
• Hormone receptor status: Not specified
• Histologically confirmed invasive breast cancer (stage I, II or IIIA) for which adjuvant therapy is appropriate
• Pathologically positive or negative nodes
• Any tumor size

STUDY CONTACT
John Robert Yarnold, Chair, Ph: 020-8661-3891
United Kingdom Coordinating Committee on Cancer
Research-ABC

OBJECTIVES:

1. Compare the disease-free and overall survival of women with early breast cancer who are randomized to stop adjuvant tamoxifen with those randomized to continue for at least 5 extra years.

PARTICIPATION CRITERIA

• Pre- or postmenopausal
• ER and/or PR-positive, -negative or unknown
• Histologically confirmed breast carcinoma that has been completely excised
• Clinically relapse-free
• Must have completed at least two years of adjuvant therapy with tamoxifen for early breast cancer AND no clear indication for or against receiving further tamoxifen
• No significant endometrial hyperplasia
• No patients with negligibly low risk of breast cancer death

STUDY CONTACT:
David J Kerr, Ph: 0121-414-3802
Cancer Research Campaign Trials Unit:
University of Birmingham
Birmingham, England, United Kingdom

OBJECTIVES:

1. Compare endometrial pathologic diagnoses for post menopausal, tamoxifen- t reated breast carcinoma patients randomly assigned to observation or cyclical medroxyprogesterone acetate (MA).
2. Compare endometrial pathologic diagnoses resulting in tamoxifen discontinuation and intermittent bleeding in breast cancer patients receiving tamoxifen and randomized to observation or cyclical MA.
3. Characterize the incidence of spontaneous regression and progression of simple or cystic hyperplasia.
4. Characterize endometrial biopsy results using different endometrial stripe width cut-off points for cases in which the width is at least 5 mm by endovaginal ultrasound for
   women receiving tamoxifen.
5. Compare changes over time in endometrial oncogene expression and receptor status for postmenopausal tamoxifen-treated breast carcinoma patients with or without prior chemotherapy randomly assigned to MA vs observation.
6. Describe associations among change in gene expression, receptor status, endometrial abnormality, length of tamoxifen exposure and prior chemotherapy.

PARTICIPATION CRITERIA

• Postmenopausal women aged 18 and over
• Candidate for adjuvant tamoxifen (Patients must start tamoxifen or have started within 28 days prior to study and plan to continue for 5 years)
• Histologically proven primary invasive stage I, IIA or IIB breast cancer (T1-3, N0-1, M0)
• Prior definitive local treatment of primary lesion
• Patients with BCT must have received or be planning to receive XRT at the start of tamoxifen treatment
• No endometrial hyperplasia, proliferative changes, complex or atypical hyperplasia or carcinoma

STUDY CONTACTS
Ronald Keith Potkul, Chair, Ph: 708-327-3314
Southwest Oncology Group
Leslie Kohman, Chair, Ph: 315-464-6321
Cancer and Leukemia Group B

OBJECTIVES:

1. Determine whether exemestane following 5 years of tamoxifen therapy is more effective than 5 years of prior tamoxifen therapy alone in prolonging disease-free survival, overall survival and time to treatment failure in postmenopausal women with resected stage I, II or IIIA breast cancer.
2. Determine the effect of tamoxifen withdrawal on bone in terms of height, fractures, total alkaline phosphatase, bone mineral density and biochemical markers in these patients.
3. Determine the effect of exemestane on bone after tamoxifen withdrawal in these patients.
4. Evaluate the quality of life of a subset of these patients.

PARTICIPATION CRITERIA

• Postmenopausal
• Histologically confirmed invasive stage I-IIIA adenocarcinoma of the breast (T1-3, N0-1, M0)
• Prior surgical resection
• Currently disease-free
• Primary tumor ER+ and/or PR+
• Borderline ER+ tumors allowed if previously treated with tamoxifen
• Previously treated with tamoxifen for 57-66 months
• Completed tamoxifen within the past 180 days
• No advanced disease at time of original diagnosis

STUDY CONTACT:
Terry Mamounas, Chair, Ph: 330-363-6281
National Surgical Adjuvant Breast and Bowel Project

OBJECTIVES:

1. Determine the disease-free survival and overall survival for women who have previously received at least five years of adjuvant tamoxifen who are randomized to receive either letrozole or placebo.
2. Evaluate the incidence of contralateral breast cancer in this patient population.
3. Evaluate the longterm clinical and laboratory safety of letrozole in terms of lipid profile, cardiovascular morbidity and mortality, incidence of bone features, in bone density and common toxic effects.

PARTICIPATION CRITERIA

• Postmenopausal
• Hormone receptor status: Positive or unknown (providing an effort has been made to determine receptor status by immunocytochemistry)
• Histologically or cytologically confirmed breast carcinoma resected at time of original diagnosis
• No evidence of metastases
• No localized or distant breast cancer recurrence. Not registered on protocol NCCTG 89-30-52, any other IBCSG protocol or any other SWOG adjuvant breast cancer protocol
• Prior adjuvant chemotherapy allowed
• No other concurrent chemotherapy
• Completed at least 4.5 but no more than 6 years of adjuvant tamoxifen after resection
• No more than 3 months since prior adjuvant tamoxifen
• No concurrent hormone replacement therapy including raloxifene, idoxifene or megestrol
• No concurrent use of other aromatase inhibitors
• Prior radiation therapy allowed

STUDY CONTACTS
Paul Edward Goss, Ph: 416-946-4534
NCIC-Clinical Trials Group
Princess Margaret Hospital
Toronto, Ontario, Canada
James N. Ingle, Chair Ph: 507-284-8432
North Central Cancer Treatment Group

Monica Castiglione-Gertsch, Chair Ph: 41-31-389-91-91
International Breast Cancer Study Group

Nicholas J. Robert, Chair Ph: 703-280-5390
Eastern Cooperative Oncology Group

Silvana Martino, Chair Ph: 310-998-3961
Southwest Oncology Group

Hyman Bernard Muss, Chair Ph: 802-847-3827
Cancer and Leukemia Group B

Martine J. Piccart-Gebhart, Chair Ph: 32-2-5413206
EORTC Breast Cancer Group

OBJECTIVES:

1. Assess the balance of risks and benefits in prolonging the duration of adjuvant tamoxifen by at least five years in patients with curatively treated breast cancer who have already had about five years of adjuvant tamoxifen.

PARTICIPATION CRITERIA

• Curatively treated carcinoma of the breast
• Must be substantial uncertainty as to whether or not to continue tamoxifen (i.e., no clear indication or definite contraindication to further treatment with tamoxifen)
• Currently taking adjuvant tamoxifen

STUDY CONTACT:
Christopher J Williams, Chair, Ph: +44-1865-226628
United Kingdom Coordinating Committee on
Cancer Research
Oxford, England, United Kingdom

OBJECTIVES:

1. Compare, in terms of disease-free and overall survival, the sequential administration of exemestane with administration of further tamoxifen until 5 years of therapy is achieved in postmenopausal women with operable breast cancer who have already received 2-3 years of adjuvant tamoxifen.
2. Compare the regimens in terms of the incidence of contralateral breast cancer and long-term tolerability of the regimens.
3. Determine the tolerability in terms of endometrial status, bone metabolism, lipid profile and coagulation profile.
4. Assess quality of life in these patients treated with these regimens.

PARTICIPATION CRITERIA

• Postmenopausal
• Histologically confirmed unilateral adenocarcinoma of the breast that was considered operable
• Estrogen receptor positive or unknown
• Must have had adequate therapy for primary disease
• Must have remained disease-free after therapy for primary disease
• Must have been receiving tamoxifen for minimum of 2 years and maximum of 3 years 1 month with no more than
  1 month break at any one time
• No evidence of local relapse or distant metastasis at any time

STUDY CONTACTS:
Raoul C Coombes, Chair, Ph: +44 (0)20 8846 14 18
International Collaborative Cancer Group

Robert Paridaens, Chair, Ph: 32-16-346902
EORTC Breast Cancer Group

Moise Namer, Chair, Ph: 33 4 92031351
Federation Nationale des Centres de Lutte Contre le Cancer