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Trastuzumab for HER2-Positive Breast Cancer: A Major Step Forward
In these studies, addition of trastuzumab to chemotherapy significantly reduced risk for a first event, including breast cancer recurrence, second primary cancer, and death.
Trastuzumab is the humanized version of a mouse monoclonal antibody with high affinity for the human epidermal growth factor receptor 2 (HER2) protein. The October 20 issue of the New England Journal of Medicine reports the results of three clinical trials assessing the use of trastuzumab in the treatment of HER2-positive breast cancer.
The first report presents results from a trial (supported by the manufacturer of trastuzumab) that enrolled women with nonmetastatic HER2-positive breast cancer who had completed surgery, with or without radiation therapy, and at least four courses of adjuvant chemotherapy. The researchers randomized 3387 women (median age, 49) to observation alone or to 1 year of intravenous trastuzumab. After a median follow-up of 1 year, risk for a first event (recurrence, contralateral tumor, second nonbreast cancer, or death) was significantly lower in the trastuzumab group (hazard ratio, 0.54). Severe congestive heart failure (CHF), a known side effect of trastuzumab, occurred in 0.5% of treated women (women with previous heart disease were excluded from the study).
The second report combines the results of two trials (each supported by trastuzumab’s manufacturer and the National Cancer Institute) that enrolled women after surgery for nonmetastatic HER2-positive breast cancer that was either node-positive, or node-negative and high risk. The researchers randomized 3676 women to chemotherapy with or without overlapping trastuzumab therapy for 1 year. After a median follow-up of 2 years, data were available for 3351 participants (68% aged 40–59). Risk for a first event (recurrence, second primary cancer, or death) was significantly lower in the trastuzumab group (HR, 0.48). At 3 years, severe CHF had occurred in 2.9% and 4.1% of trastuzumab recipients in the two trials; of 27 women who had been followed for at least 6 months after CHF onset, only 1 reported persistent symptoms (again, women with previous heart disease were excluded).
Comment: As pointed out in an accompanying commentary, 15% to 20% of invasive breast cancers are HER2-positive, and prognoses are worse with HER2-positive than with HER2-negative tumors. Results from these trials show that the addition of trastuzumab to chemotherapy reduces risk for recurrence. An editorialist called these reductions "stunning," and urged that the care of most women with HER2-positive breast cancer (including node-positive and many node-negative cancers) change immediately to include trastuzumab. We await future trials to clarify the optimal timing and duration of trastuzumab treatment, and how to minimize the agent’s cardiovascular toxicity.
— Andrew M. Kaunitz, MD
Published in Journal Watch Women's Health November 1, 2005
Citation(s):
Piccart-Gebhart MJ et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005 Oct 20; 353:1659-72.
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- Medline abstract (Free)
Romond EH et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005 Oct 20; 353:1673-84.
- Original article (Subscription may be required)
- Medline abstract (Free)
Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med 2005 Oct 20; 353:1652-4.
- Original article (Subscription may be required)
- Medline abstract (Free)
Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Engl J Med 2005 Oct 20; 353:1734-6.
- Original article (Subscription may be required)
- Medline abstract (Free)