OBJECTIVES:

1. Compare the effectiveness of adjuvant chemotherapy using standard CMF or AC vs oral capecitabine in terms of disease-free and overall survival in elderly women with
   operable adenocarcinoma of the breast.
2. Compare the quality of life and physical functioning of patients treated with these regimens.
3. Compare the toxicity of these regimens in these patients.
4. Evaluate the adherence of older patients to an oral chemotherapy regimen.

ELIGIBILITY

• Postmenopausal women age 65 and over
• Histologically proven operable adenocarcinoma of the breast
• Stage IIA or IIIA disease ( T1-3, N1, M0 or T2, N0, M0 if primary lesion at least 3 cm)
• Hormone receptor status not specified
• Must have undergone 1 of the following within the past 12 weeks: Modified radical mastectomy OR lumpectomy with axillary lymph node dissection or sentinel node biopsy. Prior full axillary dissection required if positive sentinel node(s)
• Any number of previously excised nodes allowed
• No prior chemotherapy for breast cancer
• No other concurrent chemotherapy or hormonal therapy

STUDY CONTACT
Richard L. Schilsky, Chair Ph: 773-834-3914
Cancer and Leukemia Group B

OBJECTIVES:

1. Compare the bone density in the femoral neck and lumbar spine and cholesterol levels in premenopausal women with stage I or II breast cancer treated with adjuvant
   chemotherapy with or without tamoxifen.
2. Collect information regarding breast cancer risk factors, treatment, pathology, diet, activity, weight and smoking.

PARTICIPATION CRITERIA

• Premenopausal women ages 30-50
• Histologically proven stage I or II breast cancer
• Scheduled to receive adjuvant chemotherapy +/- tamoxifen

PROTOCOL
Adjuvant chemotherapy +/- tamoxifen at the discretion of the treating physician. Baseline levels of FSH, estradiol, total cholesterol, HDL, LDL measured. Baseline bone densitometry of the femoral neck and lumbar spine. Laboratory studies and bone densitometry repeated at years 1 and 2.

STUDY CONTACT
Monica Morrow, Chair, Ph: 312-926-9039
Robert H Lurie Comprehensive Cancer Center
Northwestern University, Chicago, Illinois

OBJECTIVES:

1. Compare disease-free and overall survival in patients with stage I, II or IIIA nonmetastatic breast cancer treated with standard adjuvant therapy and zoledronate to those treated with standard adjuvant therapy alone (obser vation only).
2. Assess whether zoledronate added to standard adjuvant therapy influences the first site of recurrence in these patients.
3. Compare the first site of recurrence in PTHrP-positive patients with the first site of recurrence in PTHrP-negative patients in the group not receiving zoledronate.
4. Explore whether treatment effects are different within the PTHrP-positive and PTHrP-negative subsets.

PARTICIPATION CRITERIA

• Age, menopausal status, hormone receptor status: Not specified
• Histologically confirmed stage I, II or IIIA primary invasive adenocarcinoma of the breast. No metastatic disease
• Must have undergone modified radical mastectomy or BCT plus either ALND or SLNB
• Prior or concurrent standard systemic adjuvant therapy required
• Prior neoadjuvant chemotherapy allowed
• Combined hormonal/chemotherapy or hormonal therapy alone allowed
• Concurrent radiotherapy allowed

STUDY CONTACT
Julie R. Gralow, Chair, Ph: 206-288-1233
Southwest Oncology Group

OBJECTIVES:

1. Compare the efficacy of adjuvant AC and docetaxel given concurrently versus adjuvant AC followed by docetaxel, in terms of overall survival and disease-free survival of women with breast cancer and positive axillary lymph nodes.
2. Compare the efficacy of adjuvant doxorubicin and docetaxel versus regimens containing cyclophosphamide.
3. Compare the toxic effects of these regimens.
4. Compare the quality of life of these patients.
5. Compare the differences in amenorrhea in premenopausal women in each treatment arm and its relationship to symptoms, quality of life, disease-free survival and overall survival.

PARTICIPATION CRITERIA

• Age unspecified, hormone receptor status known
• Histologically proven invasive adenocarcinoma of the breast confined to the breast and ipsilateral axilla on clinical exam
• Stage I, II or IIIA (T1-3, N0-1, M0)
• At least one axillary lymph node with tumor on histologic exam
  - Sentinel node biopsy allowed if followed by axillary dissection
  - No suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless proven on biopsy to not be involved with tumor
• No bilateral malignancy or mass in the opposite breast, unless mass is histologically proven to be benign
• Must have undergone either a prior total mastectomy and axillary dissection (modified radical mastectomy) OR prior lumpectomy and axillary dissection
• Patients must receive radiotherapy after randomization
• Margins must be clear
• No N2 disease and/or any positive nonaxillary lymph nodes
• No metastatic disease by X-ray, MRI or biopsy
• Skeletal pain allowed if bone scan negative for metastases

STUDY CONTACT
Sandra M Swain, Chair, Ph: 301-435-9039
National Surgical Adjuvant Breast and Bowel Project

OBJECTIVES:

1. Compare the bone mineral density in the lumbar spine after 12 and 36 months of therapy with zoledronate, calcium, and cholecalciferol (vitamin D) in women with breast cancer receiving adjuvant chemotherapy.

PARTICIPATION CRITERIA

• Age: 40 and over
• Premenopausal
• Histologically confirmed adenocarcinoma of the breast by fine needle aspirate, biopsy (tru-cut, core, stereotactic), lumpectomy or modified radical mastectomy
• Stage I-III (any T, any N, M0)
• Stage IV due solely to supraclavicular node involvement allowed
• Plan to use adjuvant chemotherapy with or without tamoxifen

STUDY CONTACT
Charles L. Shapiro, Chair Ph: 614-293-7530
Cancer and Leukemia Group B

OBJECTIVES:

1. Compare the impact of adjuvant epirubicin with or without docetaxel and concurrent or sequential tamoxifen on time to relapse and overall survival in postmenopausal women with node-positive breast cancer.
2. Compare the toxic effects of these regimens in this patient population.
3. Compare the quality of life in terms of shift in long-term toxicity and differences in recuperation.
4. Compare the incidence of thromboembolic events during the first 9 months of study and the influence of such events on compliance in women treated with these regimens.

PARTICIPATION CRITERIA

• Histologically proven node-positive breast cancer
• Postmenopausal
• No distant metastases

STUDY CONTACT
Raoul C Coombes, Chair, Ph: +44 (0)20 8846 14 18
International Collaborative Cancer Group
Charing Cross Hospital
London, England, United Kingdom

OBJECTIVES:

1. Determine whether clodronate administered alone or in addition to adjuvant chemotherapy and/or tamoxifen improves disease-free survival in patients with early-stage breast cancer.
2. Determine whether clodronate reduces the incidence of skeletal metastases and nonskeletal metastases.
3. Determine whether clodronate improves overall and relapse-free survival in these patients.
4. Determine whether clodronate reduces the incidence of skeletal morbidity (e.g., skeletal fractures, hypercalcemia, skeletal pain, need for radiotherapy, spinal cord
   compression) in these patients.
5. Determine the relevance of serum markers of bone turnover as a prognostic factor for the development of bone metastases in these patients.

PARTICIPATION CRITERIA

• Histologically proven invasive adenocarcinoma of the breast Stage I or II (T1-3, N0-1, M0)
• No significant nonmalignant bone disease that is likely to interfere with interpretation of bone X-rays
• Skeletal pain allowed only if bone scan and/or roentgenological examination fails to disclose metastatic disease
  - Suspicious findings must be confirmed as benign by X-ray, MRI or biopsy

STUDY CONTACT
Alexander H. G. Paterson, Chair, Ph: 403-670-1707
National Surgical Adjuvant Breast and Bowel Project

OBJECTIVES:

1. Compare the disease-free survival and overall survival of premenopausal or early postmenopausal women with previously resected node-positive or high-risk node-negative stage I-IIIA breast cancer treated with cyclophosphamide, epirubicin and fluorouracil vs cyclophosphamide, epirubicin, filgrastim (G-CSF) and epoetin alfa followed by paclitaxel vs cyclophosphamide and doxorubicin followed by paclitaxel.
2. Compare the rate of toxic effects of these regimens. III. Compare the quality of life of patients treated with these regimens.

PARTICIPATION CRITERIA

• Age: 60 and under
• Histologically confirmed adenocarcinoma of the breast that is potentially curable
• Stage I-IIIA (T0-4 (dermal involvement only), N0-2, M0)
• Axillary node-positive or high-risk node-negative
• Previously treated with total mastectomy and axillary node dissection or partial mastectomy and axillary node dissection with planned breast radiotherapy after completion of study or sentinel node biopsy (if node-positive, must undergo axillary node dissection)
• No prior immunotherapy, chemotherapy, radiotherapy or hormonal therapy for breast cancer

STUDY CONTACT
Margot J Burnell, Chair, Ph: 506-648-6884
NCIC-Clinical Trials Group

OBJECTIVES:

1. Compare the frequency of subclinical congestive heart failure by measuring resting MUGA at 5-8 and 10-11 years after randomization in women receiving adjuvant chemotherapy with cyclophosphamide, methotrexate and fluorouracil or cyclophosphamide, doxorubicin and fluorouracil on protocol SWOG-8897.
2. Estimate the frequency of late cardiac effects (congestive heart failure, cardiac ischemic events and clinical symptoms) in these patients treated with these regimens.
3. Monitor prospectively the incidence of annual cardiac events between the fifth and tenth year after randomization of these patients to these regimens.

PARTICIPATION CRITERIA

• Age: 18 and over
• Women registered on Arm I, II, III or IV of protocol SWOG-8897 who have completed at least 1 course of assigned chemotherapy
• Completion of tamoxifen therapy not required
• Registration to current study required between 5.25-8 years or 10-11 years after randomization to protocol SWOG-8897
• Patients must be diagnosed disease-free with no prior recurrence after registration on protocol SWOG-8897

PROTOCOL
The treating physician completes patient cardiovascular and routine history and physical examination questionnaires at baseline and yearly. Patients undergo resting MUGA scans
at 5-8 and 10-11 years after registration on protocol SWOG-8897. The first scan must be performed within 3 months prior to enrollment or within 1 month after registration on the current study, and the second scan must be done in the tenth year of follow-up and within 3 months prior to enrollment or 1 month from the anniversary of registration on the current study.

STUDY CONTACT
Patricia A Ganz, Chair, Ph: 310-206-1404
Southwest Oncology Group

OBJECTIVES:

1. Determine the efficacy of adjuvant induction chemotherapy with or without cyclophosphamide and methotrexate as maintenance chemotherapy in patients with stage I, II or III breast cancer.
2. Compare the disease-free, overall and systemic disease-free survival of patients treated with these regimens.
3. Compare the toxic effects of these regimens in these patients.
4. Compare the quality of life of patients treated with these regimens.

PARTICIPATION CRITERIA

• Pre-or postmenopausal
• Histologically confirmed stage I, II or III breast cancer (T1-3, N0-1, M0. T4 disease with minimal dermal invasion allowed)
• No distant metastases
• Prior mastectomy OR BCT within past 6 weeks
• Estrogen and progesterone receptor-negative
• No prior radiotherapy for breast cancer

STUDY CONTACT
Marco Colleoni, Chair, Ph: 039-2-57489439
International Breast Cancer Study Group