BACKGROUND: Despite available treatment for early-stage breast cancer (BC), 15%-25% of patients with early-stage human epidermal growth factor receptor 2–positive (HER2+) BC eventually experience recurrence after initial treatment. The prognosis for women with HER2+ disease recurrence is poor. Most recurrences involve incurable metastatic disease. In the US, the total cost to society attributable to metastatic BC of any subtype was $12.2 billion accrued over 5 years, or $2.4 billion per year ($98,571 per patient-year). Treatment-related cost, 57% of total costs, was the largest contribution, with over $1.0 billion per year. The purpose of this study was to assess the clinical and economic burden of recurrence in patients with early-stage HER2+ BC.
METHODS: We conducted two systematic literature reviews (SLRs) and one targeted literature review (TLR) in PubMed, Embase, and Cochrane databases. The SLRs (no publication date limit; clinical SLR conducted on November 8, 2016; economic SLR conducted on October 25, 2016) searched for randomized clinical trials of neratinib and other treatments and economic data (models, utility, resource use, and cost), and the TLR (publications published from January 2006 to September 2016) searched for burden-of-illness studies in early-stage HER2+ BC.
RESULTS: A total of 4,708 abstracts (2,649 clinical SLR; 969 economic SLR; 1,090 TLR) were identified from all searches, and full-text review was conducted for 796 articles (507 clinical SLR; 151 economic SLR; 138 TLR). Of these, 159 (72 clinical SLR; 33 economic SLR; 54 TLR) followed protocol-specified criteria for inclusion. Based on clinical trials in the neoadjuvant and/or adjuvant setting, disease-free survival rates at 4 years ranged from 78% to 86%. HER2-targeting adjuvant regimens such as lapatinib added to trastuzumab and extending trastuzumab to 2 years have been unsuccessful in reducing the risk of recurrence. Women who had a recurrence, regardless of HER2 status, reported significantly poorer functioning on various quality of life (QoL) domains compared with women who remained disease free. All patients with early-stage BC, regardless of HER2 status, diagnosed with their first recurrence experienced cancer-related distress and no improvement in QoL (physical health and functioning) after 1 year. In the US, the total expected per-patient costs for all BC, regardless of HER2 status, over 10 years was $53,454 with metastatic recurrence, $61,601 with locoregional recurrence, and $61,188 with contralateral recurrence as compared with $42,005 (background costs) with no recurrence (2004 US $). The overall cost of recurrence in women with HER2+ BC in the US was estimated to be $240 million to $1.7 billion over the lifetimes of each 1-year cohort of 7,298 patients (2008 US $).
CONCLUSIONS: These results identified few studies on patients with early-stage HER2+ BC and suggest that future studies are warranted. Recurrence in women with HER2+ BC is associated with decreased QoL and high costs. After adjuvant therapy, there is still risk of recurrence, thus the clinical and economic burden remains. There is an unmet medical need in early-stage HER2+ BC, and new therapies are needed to reduce the risk of recurrence.
