Herceptin (see main web site and review article)

Women whose cancer is Her2Neu positive may benefit more from anthracycline drugs (epirubicin or adriamycin, go here) but classifying the cancer into more complex molecular subgroups may be even more important (go here.)

Herceptin® (Trastuzumab) is the first humanized antibody approved for the treatment of HER2 positive metastatic breast cancer. Herceptin is designed to target and block the function of HER2 protein overexpression.

Research has shown that women with HER2 positive metastatic breast cancer have a more aggressive disease, greater likelihood of recurrence, poorer prognosis and approximately half the life expectancy of women with HER2 negative breast cancer.

Herceptin in combination with paclitaxel is indicated for treatment of patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have not received chemotherapy for their metastatic disease. Herceptin as a single agent is indicated for the treatment of patients with metastatic breast cancer whose tumors over express the HER2 protein and who have received one or more chemotherapy regimens for their metastatic disease. The U.S. Food and Drug Administration (FDA) approved Herceptin in September 1998.Amplification of the human epidermal growth factor receptor 2 (HER2) gene results in HER2 protein overexpression. HER2 overexpression occurs in approximately 25% of breast cancer patients.
Testing for HER2 plays a key role in the management of breast cancer. ASCO Guidelines and NCCN Practice Guidelines recommend HER2 testing for all breast cancer patients. Herceptin® (Trastuzumab) is the only FDA-approved therapy specifically for the treatment of HER2 protein overexpressing metastatic breast cancer—approved for first-line use in combination with paclitaxel.

Many studies show the benefits from combing herceptin with chemotherapy in women whose cancer was HER2 positive. Also recent studies show that HER2-neu testing is more accurately done using the FISH technique

Herceptin may  be of value as an adjvant treatment but there is a risk of increased cardiotoxicity. see adjuvant herceptin trial here and here

setstats 1

Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer
Martine J. Piccart-Gebhart, M.D., Ph.D.,  for the Herceptin Adjuvant (HERA) Trial Study Team  NEJM 2005;353:1659

Background Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy.

Methods This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy.

Results Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab.

Conclusions One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer
Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast Cancer
Edward H. Romond, NEJM 2005;353:1673

Background We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer.

Methods The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2). The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclitaxel.

Results By March 15, 2005, 394 events (recurrent, second primary cancer, or death before recurrence) had been reported, triggering the first scheduled interim analysis. Of these, 133 were in the trastuzumab group and 261 in the control group (hazard ratio, 0.48; P<0.0001). This result crossed the early stopping boundary. The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years. Trastuzumab therapy was associated with a 33 percent reduction in the risk of death (P=0.015). The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831.

Conclusions Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer.