Impact of loss of HER2 positivity following neoadjuvant therapy in HER2-positive breast cancer patients on long-term prognosis: A systematic review and meta-analysis

Aims: The primary objective was to assess the impact of HER2 loss after neoadjuvant therapy on the long-term prognosis of patients with HER2-positive breast cancer. Methods: We extracted relevant studies from PubMed and Cochrane Library and performed systematic review and meta-analysis. The key eligibility criteria for the studies were as follows: included HER2-positive early breast cancer cases undergoing neoadjuvant therapy, available data on HER2 status before and after neoadjuvant therapy, and reported recurrence-related outcomes (disease-free survival/invasive disease-free survival/relapsefree survival) or overall survival. Results: Of 915 studies that were initially identified, 8 met the eligibility criteria and were included in the meta- analysis for the recurrence-related outcomes (1,917 patients with HER2 loss: 411 [21.4 %] or HER2 retained: 1,506 [78.6 %]); 4 of them reported data on overall survival (606 patients with HER2 loss: 243 [40.1 %] or HER2 retained: 363 [59.9 %]). The average follow-up duration, based on data from five out of eight studies that reported this information, was 51.6 months. HER2 loss was significantly associated with worse recurrence-related outcomes (hazards ratio [HR] 1.85, 95 % confidence interval [CI] 1.31-2.61, p = 0.0005) and worse overall survival (HR 2.37, 95 % CI 1.27-4.41, p = 0.0065). No heterogeneity or publication bias was observed in the meta-analysis. Conclusions: This study demonstrated that compared with patients with HER2 retained, those with HER2 loss had significantly higher risk of disease recurrence and worse prognosis. These findings implied the possible use of HER2 loss as a prognostic factor in patients with HER2-positive early breast cancer. Reassessment of HER2 status after neoadjuvant therapy could be valuable in predicting prognosis and may lead to reconsideration of the rational subsequent treatment.