OBJECTIVES:

1. Determine the effects of vitamin E and pentoxifylline on lymphedema in women previously treated with radiotherapy for breast cancer.
2. Assess the normal tissue injury and quality of life in patients treated with this regimen compared to placebo.

PARTICIPATION CRITERIA

• Prior diagnosis of breast cancer (TI-3, NO-1, MO)
• Prior radiotherapy to breast/chest wall plus axilla and/or stem cell transplantation
• At least five years since prior radiotherapy
• No disease recurrence
• Arm lymphedema due to prior radiotherapy
  - Reduced shoulder movement, induration in breast/chest wall, radiation-induced brachial plexopathy, symptomatic lung fibrosis or nonhealing wounds (including fractures) allowed as evidence of disability in addition to arm lymphedema
• No prior axillary surgery
• Lower axillary sampling allowed
• At least three months since prior daily vitamin E supplementation more than 30 mg/day
• No prior pentoxifylline after radiotherapy
• No concurrent ketorolac or vitamin K
• No other concurrent vitamin E supplementation

STUDY CONTACT
John Robert Yarnold, Chair, Ph: 020-8661-3891
Royal Marsden Hospital
Sutton, England, United Kingdom

OBJECTIVES:

1. Compare the effects of synchronous versus sequential adjuvant chemotherapy and radiotherapy on local recurrence, disease-free and overall survival, and treatment delay in women with early stage breast cancer.
2. Compare the safety with regard to dose intensity and toxicity of these treatment regimens.
3. Evaluate the quality of life and cosmetic outcome.

PARTICIPATION CRITERIA

• Histologically confirmed early stage, invasive, unilateral breast cancer
• Planned use of adjuvant chemotherapy and radiotherapy
• Prior or concurrent hormonal therapy allowed

STUDY CONTACT
Indy Fernando, Ph: 0121-414-3787
Cancer Research Campaign Trials Unit
University of Birmingham
Birmingham, England, United Kingdom

OBJECTIVES:

1. Determine the feasibility of concurrent paclitaxel and breast radiotherapy in women with stage II or III breast cancer who have had primary breast-conserving surgery and
   adjuvant chemotherapy.
2. Assess the cosmetic results of breast conservation after this treatment.
3. Determine the pulmonary toxicity of this regimen.

PARTICIPATION CRITERIA

• Stage II or III invasive breast cancer
• Prior breast-conserving surgery with axillary lymph node dissection required
• Adjuvant AC completed within past 3 weeks
• Prior tamoxifen allowed, no concurrent tamoxifen

PROTOCOL
Paclitaxel IV x 4 three weeks after last AC adjuvant regimen.

Concurrent XRT x approximately 6-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

STUDY CONTACT
Beth A. Overmoyer, Chair, Ph: 216-844-5176
Ireland Cancer Center
Cleveland, Ohio

OBJECTIVES:

1. Determine the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of normal tissue responses, local-regional tumor control, quality of life and
   economic consequences in women prescribed postoperative radiotherapy for early stage breast cancer.

PARTICIPATION CRITERIA

• Histologically confirmed invasive unilateral breast cancer that is considered operable. T1-3, N0-1, M0 at presentation
• Complete macroscopic excision of tumor by breast-conserving surgery or mastectomy
• No immediate breast reconstruction
• No requirement for axillary radiotherapy after greater than a Level 1 axillary dissection or after greater than 10 lymph nodes have been removed
• Prior neoadjuvant, or primary medical, therapy allowed provided subsequent surgery confirms complete macroscopic excision of residual primary tumor
• At least 2 weeks since prior cytotoxic agents
• No concurrent chemotherapy

STUDY CONTACT
John Robert Yarnold, Ph: 020-8661-3891
START Trial Management Group
Royal Marsden Hospital
Sutton, England, United Kingdom

OBJECTIVES:

1. Compare the effect of irradiation of the homolateral internal mammary and medial supraclavicular lymph node chains vs no further therapy on survival, disease-free
   survival, metastasis-free survival and cause of death in women with resected stage I/II/III breast cancer.

PARTICIPATION CRITERIA

• Histologically confirmed unilateral adenocarcinoma of the breast
• Stage I/II/III (Tx, T0-3, N0-2) disease in one of the following categories or multifocal tumors if one of the foci is in agreement with the following:
  - Centrally or medially located with any lymph node status
       › Central location defined as underlying the areola
       › Medial location defined as at least partial involvement of upper or lower medial quadrant of breast
  - Externally located with axillary node involvement
• Prior mastectomy or breast-conserving surgery and axillary dissection required
  - Sentinel node procedure as axillary intervention without further axillary surgery is allowed
  - No prior internal mammary chain dissection
  - No upper inner lesion treated with breast-conserving surgery that precludes sparing of internal mammary lymph node chain from radiotherapy volume
       › Decision at radiation oncologist’s discretion

STUDY CONTACT
Walter F. Van den Bogaert, Ph: 32-16346902
EORTC Breast Cancer Group
U.Z. Gasthuisberg
Leuven, Belgium

OBJECTIVES:

1. Compare overall and disease-free survival in women with stage II breast cancer with one to three positive nodes with or without radiotherapy following mastectomy and adjuvant chemotherapy.
2. Compare local-regional control in these patients with these treatment regimens.
3. Assess the potential toxicities of radiotherapy in this patient population.

PARTICIPATION CRITERIA

• Histologically confirmed stage II adenocarcinoma of the breast (T1-2, N1, MO)
• Primary tumor no greater than 5 cm
• At least 1 but no more than 3 positive axillary lymph nodes
• Nodes cannot be positive solely by cytokeratin staining
• Must have undergone a MRM with a level I and II axillary dissection (at least 10 nodes examined) in past 8 months
• Surgical margins negative for invasive and noninvasive ductal carcinoma
• No gross extracapsular disease or residual disease in the axilla
• Microscopic extracapsular extension allowed
• Must have received chemotherapy with or without hormonal therapy after mastectomy
• No more than 6 weeks since prior adjuvant chemotherapy
• Concurrent adjuvant chemotherapy and tamoxifen allowed

STUDY CONTACTS:
Lori J Pierce, Ph: 734-936-7810
Southwest Oncology Group
University of Michigan Medical School

Thomas Michael Pisansky, Chair, Ph: 507-284-4655
North Central Cancer Treatment Group

Stephen Barrow Edge, Chair, Ph: 716-845-5789
American College of Surgeons Oncology Group

Robert L Comis, Chair, Ph: 215-789-3645
Eastern Cooperative Oncology Group

Lawrence J Solin, Chair, Ph: 215-662-7267
Radiation Therapy Oncology Group

Lawrence Bruce Marks, Chair, Ph: 919-668-5640
Cancer and Leukemia Group B

OBJECTIVES:

1. Compare the local and regional control of the axilla obtained by complete axillary lymph node dissection versus axillary radiotherapy in sentinel lymph node-positive
   women with operable invasive breast cancer.
2. Determine whether local and regional axillary control can be obtained without axillary lymph node dissection in sentinel lymph node-negative women.
3. Compare the axillary recurrence-free survival.
4. Compare the morbidity of these three treatment regimens.
5. Compare the quality of life of these patients.

PARTICIPATION CRITERIA

• Histologically or "triple diagnosis" (palpation, mammogram or ultrasound, and cytology) confirmed operable invasive breast cancer TO-2, N0
• Only one tumor in one breast
  - Tumor between 5 and 30 mm in largest diameter by mammogram or ultrasound
• Clinically negative axillary lymph nodes
• No metastatic disease
• Concurrent treatment on EORTC PE AT trial NR 10963 allowed

STUDY CONTACT
Emiel J Rutgers, Chair, Ph: 31-20-512-2551
EORTC Breast Cancer Group
Amsterdam, Netherlands

OBJECTIVES:

1. Determine the local recurrence rate for patients with phyllodes tumors of the breast treated with local excision with negative margins and adjuvant radiation therapy.
2. Determine the survival rate in this patient population.

PARTICIPATION CRITERIA

• Histologically proven phyllodes tumors of the breast with borderline or malignant grade
  - Borderline 5 to 9 mitoses/10 high power fields (HPF), pushing or infiltrating margins, 2+ atypia
  - Malignant: 10 or more mitoses/10 HPF, predominantly infiltrating margins, usually 3+ atypia with occasional 2+ atypia
• Must have been excised with breast-conserving resection
• No positive margins
• Local recurrence of a previously excised phyllodes tumor allowed if the recurrence is in the area of the previous excision
• No prior breast carcinoma or in situ ductal carcinoma in the ipsilateral breast

PROTOCOL
Radiation therapy five days per week for a total of 28 treatments. The adjuvant radiation therapy must begin within 12 weeks of local excision or breast re-excision.

STUDY CONTACT
Richard J. Barth, Jr., Ph: 603-650-7903
Norris Cotton Cancer Center
Lebanon, New Hampshire

OBJECTIVES:

1. Compare the ability of a single fraction of radiation therapy vs multiple fractions to provide complete pain relief in patients with painful bone metastases from breast or
   prostate cancer.
2. Determine the frequency and duration of pain relief and narcotic relief after these treatments in these patient populations.
3. Compare the effect on quality of life of these two treatments in these patient populations.
4. Compare the incidence of pathologic fracture within the treatment fields after these two treatments in these patient populations.

PARTICIPATION CRITERIA

• Histologically proven breast or prostate cancer
• Radiographic evidence of bone metastasis within 8 weeks of study
• Eligible treatment sites:
  - Weight-bearing sites: pelvis (excluding pubis), femur, sacrum and/or sacroiliac joints, tibia
  - Nonweight-bearing sites: up to 5 consecutive cervical, thoracic or lumbar vertebral bodies, lumbosacral spine, up to 3 consecutive ribs, humerus, fibula, radius with/without ulna, clavicle, scapula, pubis
• If multiple sites are treated, site is included as weight-bearing if any of the sites include the pelvis, sacrum, femur or tibia
• Worst pain score of at least 5 on a scale of 10
• No skull, feet or hand metastases
• No spinal cord or cauda equina compression/effacement in vertebral metastases
• Multiple sites eligible if they can be included in no greater than 3 treatment sites
• No planned surgical fixation of the bone

STUDY CONTACTS:
William F Hartsell, Ph: 847-723-8030
Radiation Therapy Oncology Group
Lutheran General Cancer Care Center
Park Ridge, Illinois

Ivy A Peterson, Chair, Ph: 507-284-2669
North Central Cancer Treatment Group

OBJECTIVES:

1. Compare the overall survival, disease-free survival, isolated local regional disease-free survival and distant disease-free survival in women with resected, early stage, invasive breast cancer treated with breast radiotherapy with or without regional radiotherapy.
2. Compare the toxicities, including cosmetic outcomes, of these 2 regimens in these patients.
3. Compare the quality of life of patients treated with these 2 regimens.

PARTICIPATION CRITERIA

• Histologically proven invasive carcinoma of the breast without evidence of T4, N2-3, or M1 disease prior to surgery
• Node-positive or high-risk node-negative
• Prior breast-conserving therapy (BCT) and axillary node dissection or sentinel node biopsy required and must be a candidate for breast radiotherapy after BCT
• Patients with positive margins should undergo re-excision
• Patients with microscopically focally positive margins defined as no greater than 3 times high power fields are candidates for breast radiotherapy plus a boost to the lumpectomy site
• Treated with currently accepted adjuvant systemic chemotherapy and/or hormonal therapy
• High risk of regional and systemic recurrence due to one of the following:
  - Pathologically positive axillary lymph nodes
  - Pathologically negative axillary lymph nodes with one of the following:
       › Primary tumor greater than 5 cm
       › Primary tumor greater than 2 cm and less than 10 axillary lymph nodes excised and one of the following:
• Estrogen and progesterone receptor status known
  
  

STUDY CONTACT
Timothy Joseph Whelan, Ph: 905-387-9711 ext. 64501
NCIC-Clinical Trials Group
Cancer Care Ontario-Hamilton Regional Cancer Centre
Hamilton, Ontario, Canada

OBJECTIVES:

1. Determine the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of normal tissue responses, local-regional tumor control, quality of life and
   economic consequences in women prescribed postoperative radiotherapy for early stage breast cancer.

PARTICIPATION CRITERIA

• Histologically confirmed invasive unilateral breast cancer, T1-3, N0-1, M0 at presentation
• Complete macroscopic excision of tumor by breast-conserving surgery or mastectomy
• No immediate breast reconstruction
• No requirement for axillary radiotherapy after greater than a Level 1 axillary dissection or after greater than 10 lymph nodes have been removed
• At least 2 weeks since prior cytotoxic agents
• No concurrent chemotherapy

STUDY CONTACT
John Robert Yarnold, Ph: 020-8661-3891
START Trial Management Group
Royal Marsden Hospital, Sutton, England, United Kingdom

OBJECTIVES:

1. Determine if the timing of breast surgery during the menstrual cycle impacts disease recurrence, progression, or death among different racial groups in premenopausal women with stage I, II, or III breast cancer.
2. Determine if definitive breast cancer surgeries (e.g., lumpectomy or mastectomy) performed during the follicular phase result in poorer prognosis (recurrence, disease
   progression, or death) compared with surgeries performed during the midcycle or luteal phases in this patient population.

PARTICIPATION CRITERIA

• Premenopausal
• Hormone receptor status: Not specified
• Histologically confirmed stage I, II, or III primary breast cancer undergoing breast surgery
  - Invasive disease (e.g., lobular or ductal), no bilateral disease no distant metastases
• Regular menses (no amenorrhea of greater than 90 days) without hormone replacement
• Documented last menstrual period
• No preoperative chemotherapy
• No concurrent hormonal replacement therapy
• No concurrent interruptive oral contraceptive use of less than 3 months

PROTOCOL
This is a multicenter study. Patients undergo either fine needle aspiration concurrently with definitive breast surgery (mastectomy or lumpectomy) or needle directed excisional biopsy followed by definitive breast surgery. Patients undergo serum collection for hormonal analysis preoperatively, 24 hours post operatively, at days 7 and 14, and at 3 months and urine collection for hormonal analysis beginning 24 hours prior to surgery and continuing daily until the onset of the next menses. Patients complete a 30 minute telephone interview regarding medical, family, occupational, and reproductive history, and lifestyle habits (e.g., diet, exercise, environmental exposures). Beginning 24 hours prior to surgery and continuing until the onset of the next menses, patients complete a menstrual cycle journal indicating the start and length of menses. Patients undergoing mastectomy are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. Patients undergoing adjuvant therapy are followed every 3 months for 3 years, and then every 6 months thereafter or every 4 months for 2 years and then every 6 months thereafter.

STUDY CONTACT
Helena R. Chang, Ph: 310-825-2144
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California

OBJECTIVES:

1. Document menstrual phase (follicular vs luteal) by circulating hormones and menstrual history in premenopausal women at the time of primary surgery for stage I/II breast cancer.
2. Correlate menstrual phase at primary surgery with 5-year disease-free survival in these patients.
3. Compare the menstrual cycle data obtained by hormone levels and study-specific menstrual cycle history with information recorded in the general written record.
4. Compare the menstrual cycle data for these women (i.e., hormone levels and cycle history) with the data for the general population.
5. Estimate the disease-free survival of women who undergo a 2-stage surgical procedure with cancer found at both stages when the surgery is not confined to the same menstrual cycle phase.

PARTICIPATION CRITERIA

• Age: 18 to 55
• Premenopausal
• Hormone receptor status: Not specified
• Pathologically confirmed stage I/II breast cancer
• No prior neoadjuvant therapy
• Concurrent chemotherapy allowed
• At least 3 months since oral contraceptives
• Concurrent radiotherapy allowed
• Complete surgical resection required prior to entry
  - One or two stage procedure (i.e., open biopsy followed immediately or later by mastectomy or breast-conserving approach)
       › Two-step registration required for patients undergoing two-stage procedure
  - Sentinel node dissection/axillary node dissection allowed.

PROTOCOL
Patients complete a questionnaire 6 months after surgery to assess the extent of adjuvant therapy received (if any), and a questionnaire 12 months after surgery to assess recurrence of breast cancer and vital status. Patients are followed annually thereafter for 10 years.

STUDY CONTACTS
Clive S Grant, Chair, Ph: 507-284-2644
North Central Cancer Treatment Group
D Lawrence Wickerham, Chair, Ph: 412-330-4600
National Surgical Adjuvant Breast and Bowel Project

Meeting Workbook:
    - About
    - Introduction
    - Editor's note
    - General Information
    - Program Agenda
    - Controversies in Breast Cancer

Education Supplement