• Response rate [ Time Frame: D 1 ea cycle ] [ Designated as safety issue: No ]
  Response rate (complete or partial) based on all measurable ds, signs, sx, and biochemical changes related to the tumor for > 4 wks, repeat 4 wks later to document, then stage q 3 cycles
  
  

• Time to progression [ Time Frame: Day 1 of ea cycle if able to eval on PE or scan eval after 2 cycles, then q 3 cycles ] [ Designated as safety issue: No ]
  progression defined as an increase in the product of the perpendicular diameters of any measured lesion by > or = to 25% over the size present at entry on study or for pts who respond, the size at the time of max regression
  
  
• Overall survival [ Time Frame: 18 mon post protocol tx, then annually ] [ Designated as safety issue: No ]
  Pts who have ds progression or begin non protocol tx will be followed for 5 years after study entry, all others will be followed until death of patient
  
  

OBJECTIVES:

• Compare the response rate in women 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 (Herceptin®).
• Compare the response rate and quality of life of patients with HER2/neu-nonoverexpressing disease treated with 1 of these 2 paclitaxel regimens with or without trastuzumab.
• 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 of patients treated with these regimens.
• Correlate ErbB2 shed extracellular domain (ECD) with response rate, time to progression, and overall survival of patients treated with these regimens.
• Assess the patterns of ErbB2/ECD after treatment with these regimens and upon relapse in these patients.
• Compare the time to progression and survival of patients with HER2/neu-overexpressing disease treated with these regimens.
• Compare the time to progression and survival of patients with HER2/neu-nonoverexpressing disease treated with these regimens.
• 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.

OUTLINE: This is a randomized study. Patients are stratified according to prior chemotherapy for metastatic disease (none or recurrence more than 6 months after adjuvant therapy vs one or none but recurrence less than 6 months after adjuvant therapy) and HER2/neu overexpression (yes vs no). Patients are assigned to 1 of 2 treatment groups based on HER2/neu status.

• Group A (HER2/neu-nonoverexpressing): Patients are randomized to 1 of 4 treatment arms.

  • Arm I: Patients receive paclitaxel IV over 3 hours on day 1.
  • Arm II: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
  • Arm III: Patients receive paclitaxel as in arm I. Patients receive an initial loading dose of trastuzumab (Herceptin®) IV over 90 minutes on day 1 of course 1 and maintenance dose of trastuzumab IV over 30 minutes on day 1 of subsequent courses and on days 8 and 15 of all courses. Trastuzumab is administered immediately after completion of paclitaxel infusion on weeks of concurrent administration.
  • Arm IV: Patients receive paclitaxel as in arm II and trastuzumab as in arm III.

• Group B: (HER2/neu-overexpressing): Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive treatment as in arm III (group A).
  • Arm II: Patients receive treatment as in arm IV (group A). In both groups, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then at 3, 6, and 9 months.

Patients are followed at 6, 12, and 18 months and then annually for 5 years or until death.

PROJECTED ACCRUAL: A total of 580 patients will be accrued for this study within 3 years.