Treatment continues in both arms for at least two years in the absence of disease progression or unacceptable toxicity.

Patients are followed at 28 days.

OBJECTIVES:

1. Compare the efficacy with or without trastuzumab, in terms of progression-free survival, in postmenopausal women with hormone receptor-positive, HER2-overexpressing metastatic breast cancer.
2. Compare the safety profiles of these regimens.
3. Compare the overall clinical benefit rate
4. Compare the overall survival, duration of response and two-year survival of patients treated with these regimens.

PARTICIPATION CRITERIA:

• Histologically or cytologically confirmed metastatic
  breast cancer
• HER2 3+ by IHC or any degree of HER2 gene
  amplifications (at least 2 fold) by FISH
• ER and/or PR receptor+ postmenopausal women
• No concurrent chemo or hormonal therapy, nor concurrent radiotherapy or surgery to only known site of disease

STUDY CONTACT
Bernd Langer, Chair, Ph: 41-61-68-80638
Roche Global Development-Palo Alto

OBJECTIVES:

1. Determine the safety and toxicity of preoperative trastuzumab and paclitaxel followed by postoperative doxorubicin and cyclophosphamide in women with locally advanced breast cancer with HER2 overexpression.
2. Determine tumor response in these patients.
3. Assess the effect of this regimen on tumor histology and the potential molecular determinants of response in these patients.

PARTICIPATION CRITERIA:

• Age 18 and over
• Palpable primary breast cancer at least 3 cm (T2 at least
• 3 cm, T3-T4, any N), no distant metastasis (M0)
• HER2 ove re x p ression of 2+ or 3+ by IHC on core biopsy specimen using the Dako Hercep Test
• Hormone receptor status known
• No prior chemotherapy

PROTOCOL
Patients receive trastuzumab followed by paclitaxel on day 1. Then q 7 days x 10 courses in the absence of disease progression or unacceptable toxicity.

Modified radical mastectomy or a lumpectomy with AND.
Beginning 14 days after surgery, patients receive doxorubicin and cyclophosphamide over 15-30 minutes on day 1. Treatment repeats q 21 days x 4 courses.
After chemotherapy, patients with hormone receptor-positive
disease receive tamoxifen x 5 years.

STUDY CONTACT
Matthew D. Volm, Chair, Ph: 212-263-7223
NYU School of Medicine’s Kaplan Comprehensive
Cancer Center
New York, New York

AC=doxorubicin/cyclophosphamide; T=paclitaxel;
H=trastuzumab

ER/PR-positive patients receive tamoxifen for 5 years.

Patients > 50 y.o. or who are ER/PR-negative or indeterminable and have received prior
chemopreventive tamoxifen may be treated with tamoxifen at the investigator’s discretion.

Lumpectomy patients undergo XRT x 5-6 weeks after chemotherapy and concurrently with trastuzumab.

OBJECTIVES:

1. Compare the cardiotoxicity of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab (Herceptin) in patients with operable, node-positive breast cancer that overexpresses HER2.
2. Compare the effect of these regimens, with or without tamoxifen, on disease-free and overall survival.

PARTICIPATION CRITERIA:

• Invasive adenocarcinoma, stage IIA, IIB or IIIA (T1-3, N0-1, M0)
• Clinically confined to the breast and ipsilateral axilla
• At least 1 axillary node histologically positive
• No lymph nodes clinically fixed to each other or to other structures (N2 disease)
• HER2 strongly positive (3+ by immunostain or FISH). One third or more invasive tumor cells must stain positive. Submission of tumor block required
• Must have undergone ALND and either mastectomy OR lumpectomy. SND allowed, if followed by ALND
• No bilateral malignancy. No contralateral mass or mammographic abnormality unless proven benign
• No suspicious palpable nodes in the contralateral axilla, supraclavicular or infraclavicular unless histologically proven not to be involved with tumor
• No ulceration, erythema, infiltration of the skin or chest wall, peau d’orange, or skin edema. Tethering or dimpling of the skin or nipple inversion allowed
• No concurrent hormonal therapy, SERM therapy, or XRT (except as specified in study)

STUDY CONTACT
Edward H. Romond, Chair, Ph: 859-323-5038
National Surgical Adjuvant Breast and Bowel Project

OBJECTIVES:

1. I. Compare the response rate in patients with inoperable, recurrent, or metastatic breast cancer treated with paclitaxel via one hour infusion every week vs 3 hour
   infusion every 3 weeks, regardless of HER2-Neu status and assignment to trastuzumab.
2. Compare the response rate and quality of life in patients with HER2-Neu non-overexpressing disease treated with 1 of these 2 paclitaxel regimens with or without
   trastuzumab.
3. Correlate amplification and overexpression of the growth factor receptor ErbB2 by immunohistochemistry and fluorescent in situ hybridization (FISH) with response
   rate, time to progression, and overall survival in patients treated with 1 of these 2 paclitaxel regimens with or with out trastuzumab.
4. Correlate ErbB2 shed extracellular domain (ECD) with response rate, time to progression, and overall survival in patients treated with 1 of these 2 paclitaxel regimens with or without trastuzumab.
5. Assess the patterns of ErbB2/ECD after treatment and upon relapse.
6. Compare the time to progression and survival of patients with HER2-Neu overexpressing disease treated with 1 of these 2 paclitaxel regimens with rastuzumab.
7. Compare the time to progression and survival in patients with HER2-Neu nonoverexpressing disease treated with 1 of these 2 paclitaxel regimens with or without trastuzumab.
8. Compare the cardiac toxicity of these regimens as measured by changes in left ventricular ejection fraction from baseline to follow up measurements in these
   patients.

PARTICIPATION CRITERIA:

• 18 years and over
• Histologically proven inoperable, recurrent, or metastatic adenocarcinoma of the breast
• Known HER2-neu status
• Measurable disease

STUDY CONTACT
Andrew D. Seidman, Chair, Ph: 212-636-5875
Cancer and Leukemia Group B

AC=doxorubicin/cyclophosphamide; T=docetaxel;
H=trastuzumab

ER/PR+ patients receive tamoxifen.
XRT 3-8 weeks after completion.

OBJECTIVES:

1. Compare disease-free survival in women with HER2-neu-expressing, node+ or high-risk node-negativeoperable breast cancer treated with adjuvant doxorubicin, cyclophosphamide, and docetaxel with or without trastuzumab versus trastuzumab, docetaxel, and either carboplatin or cisplatin.
2. Compare overall survival of patients.
3. Compare the toxic effects (including cardiac).
4. Compare quality of life of patients treated with these regimens
5. Compare pathologic, molecular markets for predicting efficacy.
6. Compare peripheral levels of shed HER2 ECD with FISH in predicting outcome.

PARTICIPATION CRITERIA:

• 18-70 years old
• Histologically confirmed breast cancer (T1-3, N0-1, M0)
• Node+ disease OR high-risk node-disease with > 1 of the following: tumor size > 2 cm, ER- and/or PR-negative, histologic and/or nuclear grade 2-3
• No bilateral invasive breast cancer
• HER2-neu gene amplification by FISH
• Mastectomy or BCT AND ALN assessment within the past 60 days
• Clear margins histologically

STUDY CONTACT
Linnea Chap, Chair, Ph: 310-206-6144
Jonsson Comprehensive Cancer Center, UCLA

OBJECTIVES:

1. Compare efficacy and toxicity of first-line trastuzumab alone followed at disease progression by the combination of trastuzumab and paclitaxel versus first-line combination of both drugs in women with HER2 overexpressing metastatic breast cancer.
2. Compare quality of life of these patients.
3. Investigate the predictive value of serum HER2/neu ECD levels on clinical outcome, the effects of trastuzumab on estrogen receptor, and the association of immunoprofiles of erbB-1, erbB-2, erbB-3, and erbB-4 with clinical outcome in this patient population.

PARTICIPATION CRITERIA:

• Histologically confirmed HER2 overexpressing metastatic breast carcinoma
• Clinically or radiologically measurable or evaluable disease
• Bidimensionally or unidimensionally measurable lesions
• No cumulative dose of doxorubicin greater than 240 mg/m2
• No cumulative dose of epirubicin greater than 360 mg/m2
• No prior taxanes

OBJECTIVES:

1. Compare the disease-free survival of patients with HER-2 overexpressing breast cancer when treated with doxorubicin plus cyclophosphamide followed by paclitaxel
   with or without trastuzumab (Herceptin).
2. Compare the cardiotoxicities of these treatments.
3. Compare the overall survival of these patients when treated with one of these regimens.
4. Determine whether higher levels of shed extracellular domain or autoantibodies to HER-2 and HER-1 measured in the serum prior to treatment are prognostic for disease-free and overall survival.
5. Determine the concordance of HER-2 overexpression with
   disease-free and overall survival in this patient population.

PARTICIPATION CRITERIA:

• Menopausal status: Any status
• Histologically confirmed adenocarcinoma of the breast with one or more positive lymph nodes (T1-3, pN1-2, M0)
• No cN2 disease allowed
• Metaplastic carcinoma and pN2 disease allowed
• HER-2/neu 3+ (0-2+ allowed if FISH+ assay)
• No locally advanced (T4) tumors.
• No dermal lymphatic involvement without clinical inflammatory changes
• No bilateral invasive carcinoma or ductal carcinoma in situ
• No gross or microscopic disease at margins
• No concurrent hormonal therapy or raloxifene
• No more than four weeks of prior tamoxifen allowed
• No prior radiotherapy for breast cancer

STUDY CONTACTS
Edith A. Perez, Chair, Ph: 904-953-7283
North Central Cancer Treatment Group
Robert L. Comis, Chair Ph: 215-789-3645
Eastern Cooperative Oncology Group
Peter A. Kaufman, Chair Ph: 603-650-6700
Cancer and Leukemia Group B
Silvana Martino, Chair Ph: 310-998-3961
Southwest Oncology Group

PHASE II PILOT STUDY OF TRASTUZUMAB (HERCEPTIN) PLUS DOCETAXEL IN WOMEN WITH HER2-NEU OVEREXPRESSING RECURRENT OR METASTATIC BREAST CANCER Open Protocol

PROTOCOL IDS: VU-VCC-BRE-9823; NCI-G00-1830

STUDY CONTACT:
David Horton Johnson, Chair Ph: 6153439454
Vanderbilt-Ingram Cancer Center

PHASE II RANDOMIZED STUDY OF PACLITAXEL, CARBOPLATIN, AND TRASTUZUMAB (HERCEPTIN) AS FIRST-LINE CHEMOTHERAPY IN WOMEN WITH OVEREXPRESSED HER-2, METASTATIC BREAST CANCER Open Protocol

PROTOCOL ID: NCCTG-983252

STUDY CONTACT:
Edith A. Perez, Ph: 904-953-7283
Mayo Clinic Cancer Center
Rochester, Minnesota

PHASE II STUDY OF CELECOXIB AND TRASTUZUMAB (HERCEPTIN) IN WOMEN WITH HER2/NEU OVEREXPRESSING METASTATIC BREAST CANCER THAT IS REFRACTORY TO PRIOR TRASTUZUMAB Open Protocol

PROTOCOL IDS: MSKCC-00078; NCI-G00-1869

STUDY CONTACT:
Clifford A. Huddis, Ph: 212-639-6483
Memorial Sloan-Kettering Cancer Center
New York, New York

PHASE II STUDY OF DOXORUBICIN HCL LIPOSOME AND DOCETAXEL WITH OR WITHOUT TRASTUZUMAB (HERCEPTIN) IN WOMEN WITH METASTATIC BREAST CANCER Open Protocol

PROTOCOL IDS: E-3198

STUDY CONTACT:
Antonio C. Wolff, Chair, Ph: 410-614-4192
Eastern Cooperative Oncology Group

PHASE I/II STUDY OF CAPECITABINE, PACLITAXEL, AND TRASTUZUMAB (HERCEPTIN) IN PATIENTS WITH METASTATIC BREAST CANCER Open Protocol

PROTOCOL IDS: UNC-9904; NCI-G00-1834

STUDY CONTACT:
Frances A. Collichio, Ph: 919-966-4431
Lineberger Comprehensive Cancer Center, UNC
Chapel Hill, North Carolina

PHASE I/II STUDY OF TRASTUZUMAB (HERCEPTIN) FOLLOWING HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS PERIPHERAL BLOOD STEM CELL RANSPLANTATION IN PATIENTS WITH METASTATIC BREAST CANCER Open Protocol

PROTOCOL IDS: BIH-99-12; NCI-V00-1610; BIH-W-99-0053-FB

STUDY CONTACT:
David Avigan, Ph: 617-667-9920
Beth Israel Deaconess Medical Center
Boston, Massachusetts

PHASE I/II STUDY OF DOXORUBICIN HCL LIPOSOME AND TRASTUZUMAB (HERCEPTIN) IN WOMEN WITH ADVANCED HER-2/NEU-OVEREXPRESSING BREAST CANCER Open Protocol

PROTOCOL IDS: NYU-0012; NCI-G00-1878; ALZA-00-001-ii

STUDY CONTACT:
Franco M. Muggia, Ph: 212-263-6485
NYU School of Medicine’s
Kaplan Comprehensive Cancer Center

PHASE I/II STUDY OF DOXORUBICIN HCL LIPOSOME AND TRASTUZUMAB (HERCEPTIN) IN WOMEN WITH LOCALLY ADVANCED, INFLAMMATORY, OR METASTATIC BREAST CANCER Open Protocol

PROTOCOL IDS: MSKCC-99054; NCI-G00-1684; LIPO-D9905

STUDY CONTACT:
Clifford Hudis, Ph: 212-639-6483
Memorial Sloan-Kettering Cancer Center
New York, New York

PHASE II STUDY OF TRASTUZUMAB (HERCEPTIN) AND PACLITAXEL IN PATIENTS WITH HER2 OVEREXPRESSING METASTATIC BREAST CANCER Open Protocol

PROTOCOL IDS: NCI-99-C-0121; NCI-T98-0087

STUDY CONTACT:
Susan Elaine Bates, Ph: 301-402-0984
Medicine Branch
Bethesda, Maryland

PHASE II STUDY OF TRASTUZUMAB (HERCEPTIN) AND RADIO-THERAPY IN WOMEN WITH STAGE III OR IV INVASIVE PRIMARY CARCINOMA OF THE BREAST THAT CONTINUES TO OVEREXPRESS HER2 FOLLOWING NEOADJUVANT CHEMOTHERAPY Open Protocol

PROTOCOL IDS: UNC-9925; NCI-G00-1835

STUDY CONTACT:
Carolyn Sartor, Ph: 919-966-7700
Lineberger Comprehensive Cancer Center, UNC
Chapel Hill, North Carolina

PHASE II STUDY OF TRASTUZUMAB (HERCEPTIN) PLUS INTER-LEUKIN-2 IN PATIENTS WITH METASTATIC BREAST CANCER WHO HAVE FAILED PRIOR TRASTUZUMAB Open Protocol

PROTOCOL IDS: OSU-99H0192, NCI-195

STUDY CONTACT:
Charles L. Shapiro, Chair, Ph: 614-293-7530
Arthur G. James Cancer Hospital - Ohio State University
Columbus, Ohio

PHASE I STUDY OF VINORELBINE AND TRANSTUZUMAB (HERCEPTIN) IN PATIENTS WITH HER-2/NEU OVEREXPRESSINIG REFRACTORY LOCALLY ADVANCED OR METASTATIC BREAST CANCER Open Protocol

PROTOCOL IDS: DMS-9904; NCI-G01-1932

STUDY CONTACT:
Peter A. Kaufman, Chair Ph: 603-650-6700
Norris Cotton Cancer Center
Lebanon, New Hampshire, U.S.A.

PHASE I STUDY OF INTERLEUKIN-12, PACLITAXEL, AND TRASTUZUMAB (HERCEPTIN) IN PATIENTS WITH HER2/NEU-OVEREXPRESSING CANCER Open Protocol

PROTOCOL IDS: OSU-99H0326, NCI-84

STUDY CONTACT:
William Edgar Carson, III, Chair Ph: 614-293-6306
Arthur G. James Cancer Hospital - Ohio State University

PHASE I/II STUDY OF TRASTUZUMAB (HERCEPTIN) AND ZD 1839 IN PATIENTS WITH METASTATIC BREAST CANCER THAT OVEREXPRESSES HER2-NEU Open Protocol

PROTOCOL IDS: E-1100

STUDY CONTACT:
Carlos Luis Arteaga, Chair Ph: 615-322-4967
Eastern Cooperative Oncology Group

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

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