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Trastuzumab Reduces Mortality in HER2–Positive Breast Cancer
Am Fam Physician. 2007 Jul 1;76(1):127-128.
Background: Fifteen to 25 percent of breast cancers show an overexpression of the human epidermal growth factor 2 (HER2) transmembrane growth factor receptor. Women who have an amplification of the HER2 gene and an overexpression of the receptor tend to have more aggressive clinical progression of breast cancer and higher mortality. The humanized monoclonal antibody trastuzumab (Herceptin) targets the HER2 receptor and has been associated with increased survival in patients with HER2–positive metastatic breast cancer. During limited follow-up, the results of five large trials of trastuzumab as an adjunctive therapy suggested that early risk of recurrence in patients with HER2–positive breast cancer could be reduced by 50 percent. Smith and colleagues report the results of a longer follow-up from the large Herceptin Adjuvant study in which women were treated for one year with trastuzumab.
The Study: The Herceptin Adjuvant study randomized women with confirmed HER2–positive early stage breast cancer to observation alone or to one or two years of trastuzumab therapy following surgery and adjuvant chemotherapy. Women in the intervention groups received an initial dose of 8.0 mg per kg of trastuzumab followed by 6.0 mg per kg of trastuzumab every three weeks. During the study, 97 patients (5.7 percent) in the observation group and 58 (3.4 percent) of those randomized to one year of therapy were lost to follow-up, and 172 women stopped therapy prematurely. This study reports on the participants who received one year of treatment after a median follow-up time of 23.5 months.
Results: The characteristics of the 1,698 women in the observation group were similar to the 1,703 who received one year of trastuzumab therapy. After nearly two years of follow-up, 539 events were recorded. The unadjusted hazard ratio for the risk of an event, which was 0.64 (95% confidence interval [CI], 0.54 to 0.76), was significantly reduced in patients who had been treated with trastuzumab. More deaths occurred in the observation group, and the hazard ratio for risk of death, 0.66 (95% CI, 0.47 to 0.91), was reduced significantly following treatment. The reductions in distant metastases and time to distant metastases also were significantly improved in women who received trastuzumab. Conversely, women treated with trastuzumab experienced significantly more severe adverse effects (6 percent compared with 11 percent). The most common serious adverse events were hypertension (12 patients), depression (8 patients), diarrhea (7 patients), and congestive heart failure (7 patients).
Conclusion: Women who received one year of adjunctive trastuzumab therapy showed significant survival benefit after a median follow-up of two years, and no specific subgroups of patients were identified to benefit disproportionately. The risk of cardiotoxicity appeared to be low. Nevertheless, the authors note several important questions that remain, including the optimal duration of trastuzumab therapy and if it should be given concurrently or sequentially with taxane chemotherapy.
Smith I, et al. for the HERA study team. 2-Year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. January 6, 2007;369:29–36.
Copyright © 2007 by the American Academy of Family Physicians.
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