Estimating recurrences prevented from using trastuzumab in adjuvant breast cancer in the United States.
Authors: Danese M , Lalla D , Brammer M , Doan Q , Knopf K 
Published: December 2010

Abstract #2107

Introduction: Trastuzumab was recently approved for adjuvant use in HER2+ breast cancer. Adjuvant treatment should result in a reduction in recurrences, but this has not been estimated from a US population perspective. Methods: We estimated the number of HER2+ breast cancers in the US in 2005 using SEER data. Because HER2 status is not available in SEER, the number of HER2+ patients was estimated using the known relationship between HER2 status and both estrogen receptor (ER) and progesterone receptor (PR) status. Patients with no ER or PR results were assumed to have no HER2 testing. HER2+ proportions for remaining ER+/PR+, ER+/PR-, ER-/PR+ and ER-/PR- patients were estimated from published data and applied to patients diagnosed in the 17 SEER registries. The resulting rates were applied to the 2005 US female population counts. Estimated HER2+ patient counts were stratified by nodal status (+/-), and age (30-50, 50-70, and &gt;70 years). Patients with significant underlying cardiovascular (CV) disease were assumed not to use trastuzumab. Underlying recurrence rates were pooled across studies that compared doxorubicin and cyclophosphamide followed by a taxane (AC-T) versus the same regimen plus 52 weeks of trastuzumab (AC-TH). Rates were stratified by nodal status. The relative risk of recurrence with trastuzumab (0.53) was assumed to be constant across subgroups based on published data, and assumed to persist for 5 years. One study (NSABP B-31) estimated the proportion experiencing a CV event (primarily defined as ejection fraction decline below threshold or dyspnea with normal activity) based on 5-year follow-up. Probabilistic model inputs were used to reflect the likelihood of possible values where possible. The results were run using 5,000 replications and reported as the mean and middle 95% of the distribution using @Risk (Palisade Corp., Ithaca, NY). Results: The model estimated that there are approximately 28,500 (95% interval 26,400 to 31,500) patients who could be diagnosed with HER2+ breast cancer in one year in the US, 6,128 (95% interval 4,292 to 8,600) of whom will have a recurrence within 5 years, and up to 2,619 of whom (95% interval 1,506 to 3,701) who could be prevented from disease recurrence with trastuzumab use. The number of patients who might experience a CV event is approximately 941 (95% interval 510 to 1,395) giving a ratio of 2.7 recurrences prevented for every CV event (95% interval 1.4 to 5.6). Conclusion: Trastuzumab is capable of preventing at least 2,600 recurrences within 5 years after its initial year of use. Its most clinically important side effect, a CV event, is likely to appear once for every 2.7 recurrences that are prevented, although many cases are asymptomatic and reversible. Extrapolated over 20 years, targeting HER2+ tumors in the adjuvant setting could prevent as many as 50,000 HER2+ patients from recurrence with important clinical, humanistic and economic consequences for patients, physicians and payors.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2107.