• Crump M, Trudeau M, Sinclair S, O'Malley F, Breast Cancer Disease Site Group. The role of trastuzumab (Herceptin®) in the treatment of women with HER2/neu-overexpressing metastatic breast cancer. Toronto (ON): Cancer Care Ontario (CCO); 2005 Nov 8. 28 p. (Practice guideline report; no. 1-15). [55 references]

Question #1 -- Compared with Chemotherapy Alone, Does Trastuzumab in Combination with Chemotherapy Improve Clinically Meaningful Outcomes?

• Trastuzumab in combination with either six cycles of three-weekly paclitaxel (175mg/m²) or six cycles of three-weekly docetaxel (100mg/m²) is recommended as a first-line therapy for women with human epidermal growth factor receptor 2 (HER2)/neu-overexpressing metastatic breast cancer.
• Due to concerns regarding cardiotoxicity, trastuzumab is not recommended in combination with doxorubicin.
• Due to the lack of randomized trial data, no definitive recommendation regarding the use of trastuzumab with other combinations outside of clinical trials can be made at this time.

Question #2 -- Compared with Placebo or Observation, Does Single-Agent Trastuzumab Therapy Improve Clinically Meaningful Outcomes?

• Due to the lack of randomized trial data, no definitive recommendations regarding the use of single-agent trastuzumab therapy can be made at this time.

Question #3 -- What Is the Best Way to Identify Women Who Will Benefit from Trastuzumab Therapy?

• Trastuzumab combination therapy is most likely to be effective in women with the highest level of HER2/neu protein overexpression, as indicated by an immunohistochemistry score of 3+ (moderate/strong membrane staining in at least 10% of tumour cells) or by HER2/neu gene amplification (defined as HER2/CEP17 >2 by fluorescence in situ hybridization).

Question #4 -- What Are the Adverse Events Associated with Trastuzumab Therapy?

• Women should be monitored for signs and symptoms of congestive heart failure during treatment with trastuzumab.

Question #5 -- What Are the Optimal Dose, Schedule, and Duration for Trastuzumab Therapy?

• Regardless of combination, trastuzumab should be initiated at 4mg/kg and continued at 2mg/kg weekly until disease progression or unacceptable toxicity.

None provided

The recommendations are supported by randomized controlled trials and non-randomized trials.

• Crump M, Trudeau M, Sinclair S, O'Malley F, Breast Cancer Disease Site Group. The role of trastuzumab (Herceptin®) in the treatment of women with HER2/neu-overexpressing metastatic breast cancer. Toronto (ON): Cancer Care Ontario (CCO); 2005 Nov 8. 28 p. (Practice guideline report; no. 1-15). [55 references]

Not applicable: The guideline was not adapted from another source.

2005 Nov 8

Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]

The Program in Evidence-based Care (PEBC), is a Province of Ontario initiative sponsored by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Cancer Care Ontario
Ontario Ministry of Health and Long-Term Care

Provincial Breast Cancer Disease Site Group

The members of the Breast Cancer Disease Site Group (DSG) disclosed potential conflicts of interest relating to the topic of this practice guideline. Two of the four lead authors reported related research involvement and research funding. One author (MC) reported receiving grant or research funding from Roche Canada, and one (MT) reported the receipt of honoraria from that same company.

None available

This summary was completed by ECRI on January 25, 2006. The information was verified by the guideline developer on February 23, 2006.