OBJECTIVES:

1. Compare the disease-free survival and overall survival in patients with node-positive or high-risk node-negative operable stage II or IIIA breast cancer treated with docetaxel
   or paclitaxel after AC.
2. Determine whether the weekly administration of paclitaxel or docetaxel for 12 weeks improves disease-free survival and overall survival when compared with the conventional schedule of every 3 weeks for 4 courses after AC.
3. Compare the toxic effects of docetaxel and paclitaxel when administered weekly for 12 weeks versus every 3 weeks for 4 courses in these patients.
4. Compare the toxicity of paclitaxel administered every 3 weeks for 4 courses or weekly for 12 weeks to that of docetaxel administered on the same schedules in these patients.
   

PARTICIPATION CRITERIA:

• 18 and over, any hormone receptor status
• Histologically confirmed operable stage IIA, IIB or IIIA adenocarcinoma of the breast with histologically involved lymph nodes OR high-risk node-negative disease
  - Tumor at least 2.1 cm in diameter for node-negative disease
  - Bilateral breast disease allowed if at least 1 primary tumor meets the criteria above
• Must have had at least 6 axillary lymph nodes removed at dissection and at least one node positive OR sentinel node biopsy negative for metastasis (SNLB+ allowed if enrolled on American College of Surgery Trial Z0011 and have been randomized to receive no axillary dissection)
• Tumor-free margins at least 1 mm for both invasive and noninvasive carcinoma except for LCIS (< 1 mm allowed) • Concurrent enrollment on ACS Z0010, Z0011 or NSABP B-32 allowed

STUDY CONTACTS
Joseph A Sparano, Chair, Ph: 718-904-2555
Eastern Cooperative Oncology Group
Edith A Perez, Chair, Ph: 507-284-5369
North Central Cancer Treatment Group
Silvana Martino, Chair, Ph: 310-998-3961
Southwest Oncology Group
Vicky Eileen Jones, Chair, Ph: 858-657-8710
Cancer and Leukemia Group B

OBJECTIVES:

1. Compare the response rates in women with inflammatory or estrogen receptor-negative, locally advanced breast cancer treated with neoadjuvant doxorubicin and
   cyclophosphamide with vs without filgrastim (G-CSF).
2. Compare the toxic effects of these regimens.
3. Compare the delivered dose intensity of these regimens.
4. Evaluate the association between microscopic pathologic complete response and clinical complete response at the primary tumor site in these patients.

PARTICIPATION CRITERIA:

• Age and menopausal status not specified
• Histologically confirmed inflammatory or locally advanced breast cancer
  • Stage IIB (T3, N0, M0), IIIA (T3, N1-2, M0 or T0-2, N2, M0) or IIIB (T4, any N, M0 or any T, N3, M0)
• Un resectable or otherwise appropriate for neoadjuvant therapy
• Confirmed by core needle or incisional biopsy
• Estrogen receptor-negative if disease is not inflammatory

STUDY CONTACT
Georgiana Kehr Ellis, Chair, Ph: 206-288-2048
Southwest Oncology Group

OBJECTIVES:

1. Compare neoadjuvant fluorouracil, epirubicin and cyclophosphamide vs docetaxel and epirubicin followed by radiotherapy and surgery in women with locally advanced,
   inflammatory or large operable breast cancer.
2. Compare the progression-free survival with these regimens.
3. Compare the distant metastasis-free survival and survival of patients treated with these regimens.
4. Compare clinical and pathological responses to these regimens.
5. Compare the toxicity of these regimens in these patients.
   

PARTICIPATION CRITERIA:

• Age 70 and under
• Histologically confirmed breast cancer
• Locally advanced or inflammatory disease (T4a-d, any N, M0; or any T, N2 or N3, M0)
• Large T2 or T3 breast cancer requiring tumor shrinkage prior to BCT

STUDY CONTACTS
Herve Bonnefoi, Chair, Ph: 011-41-22-382-33-11
EORTC Breast Cancer Group

Jonas Bergh, Chair, Ph: 46-8-51776279
Swedish Breast Cancer Group

Barbara Muster, Chair Ph: 011-41-31-389-9191
Swiss Institute for Applied Cancer Research

OBJECTIVES:

1. Compare the response to neoadjuvant therapy with fluorouracil, doxorubicin and cyclophosphamide (FAC) vs cyclophosphamide, methotrexate and fluorouracil (CMF) in patients with stage III breast cancer.
2. Compare the rate of breast conservation and local-regional control with these two regimens.
3. Assess the disease-free and overall survival.
4. Assess the toxic effects, cosmetic results after conservative surgery, quality of life and patient compliance.
   

PARTICIPATION CRITERIA:

• Age 21-75
• Breast cancer histologically confirmed, measurable, stage III breast cancer
• No inflammatory breast cancer

  * In both arms, pts with resectable disease after the 3rd course of chemotherapy undergo quadrantectomy with AND or MRM, folllowed by 6 additional courses of the chemotherapy regimine to which they were initially randomized. Patients without distant metastasis receive locoregional radiotherapy concurrently with postoperative chemotherapy. Patients on both arms with unresectable dz after the initial 3 courses of
  chemotherapy receive locoregional radiotherapy then surgical resection (if feasible).

STUDY CONTACT
Bernardo A. Leone, Chair, Ph: 54-299-4436396
Grupo Oncologico Cooperativo del Sur

OBJECTIVES:

1. Evaluate the feasibility of using cDNA microarray as a measure of a tumor’s biological response to neoadjuvant docetaxel and capecitabine followed by surgery and adjuvant doxorubicin and cyclophosphamide by characterizing the cDNA expression patterns before and after chemotherapy in patients with stage II or III breast cancer.
2. Determine the toxicities of this regimen in these patients.
3. Determine the clinical and pathologic response rate.
   
   

PARTICIPATION CRITERIA:

• Hormone receptor status known
• Histologically or cytologically confirmed stage II or III breast cancer (Tumor size greater than 2 cm)
• Prior biopsy allowed if adequate tissue remains for 2nd biopsy

STUDY CONTACT
JoAnne Zujewski, Chair, Ph: 301-402-0985
Center for Cancer Research Medicine Branch
Bethesda, Maryland

OBJECTIVES:

1. Compare the overall survival and time to loco-regional failure in women with locally advanced breast cancer treated with breast-conserving local therapy vs mastectomy followed by radiotherapy after they have received prior induction chemotherapy.
2. Compare the quality of life of patients treated with these regimens.
   
   

PARTICIPATION CRITERIA:

• Locally advanced breast cancer
• T3 inoperable, N0-N2
• Any T, N2
• T4, N0-N2
• Inflammatory breast carcinoma
• Prior treatment, 4-6 courses standard induction chemotherapy / active investigational regimens completed within the past 4 weeks
• Residual tumor size less than 5 cm
• No fixed axillary lymph nodes
• No multifocal or bilateral breast cancer
• No clinical suspicion of extensive ductal carcinoma in situ
• No unresolved skin edema
• No distant metastases
• Positive bone scan allowed provided there are no bone metas-tases on x-ray

STUDY CONTACT
England
Marie Emson, Ph: +44 (0) 2088461478
Charing Cross Hospital
London, England, United Kingdom

OBJECTIVES:

1. Determine the time to locoregional recurrence, time to completion of treatment, and overall survival in women with HER2+ stage IIIA or IIIB or regional stage IV breast cancer treated with doxorubicin and cyclophosphamide (AC) with or without dexrazoxane, followed by paclitaxel with or without trastuzumab (Herceptin), followed by surgery and radiotherapy with or without trastuzumab.
2. Determine whether addition of trastuzumab to paclitaxel therapy improves response at 24 weeks of therapy.
3. Determine whether addition of trastuzumab to paclitaxel therapy increases the rate of cardiotoxicity.
4. Determine whether addition of dexrazoxane to AC compromises response.
5. Determine whether addition of dexrazoxane to AC reduces the rate of cardiotoxicity.
6. Determine whether long-term trastuzumab after local therapy improves disease-free survival.
7. Determine whether long-term trastuzumab after local therapy increases the rate of cardiotoxicity.
8. Determine the occurrence of any grade 3 or higher toxicity, second malignancies, acute myelogenous leukemia, or myelodysplastic syndrome.
9. Determine the eventual rate of breast conservation in those patients considered candidates for breast conservation prior to neoadjuvant therapy.
10. Determine the clinical response after AC with or without dexrazoxane and the clinical/mammographic/ultrasound response after paclitaxel with or without rastuzumab, compared to the pathologic response at definitive surgery.

PARTICIPATION CRITERIA:

• 18 years and older
• Histologically confirmed primary infiltrating adenocarcinoma of the breast confirmed by core needle biopsy or incisional biopsy
• Amplification of HER2 by FISH OR IHC 3+
• Staging criteria after complete clinical and radiographic staging:
  - T3, N1, M0 OR
  - Any T, N2 or N3, M0 OR
  - T4, any N, M0 including clinical or pathological inflammatory disease OR
  - regional stage IV disease with supraclavicular or infraclavicular lymph nodes as only site of metastasis
  
• Measurable or evaluable disease
• Prior DCIS of the ipsilateral breast allowed if treated with excision only
• Metaplastic carcinoma allowed
• Synchronous bilateral primary disease allowed (provided at least one cancer meets staging criteria)
• No dermal lymphatic involvement with clinical inflammatory changes

STUDY CONTACT
Mark L. Graham, Chair, Ph: 919-859-6631
Cancer and Leukemia Group B