Comparison of therapy benefit from standard anti-HER2-directed approaches in metastatic breast cancer (MBC) between initially-HER2 positive patients and patients initially HER2-negative with switch to HER2-positive

Background 5% of initially HER2-negative breast cancer patients switch to HER2-positive. Whether there is a difference in benefit from standard HER2-targeted therapies between patients initially HER2-positive and patients switching from negative to positive is unclear.

Methods PRAEGNANT is a prospective advanced breast cancer registry (NCT02338167). We compared progression-free survival (PFS) with standard HER2-targeted therapies between patients with tumors initially HER2-negative and switched to HER2-positive and patients with tumors that were initially HER2-positive adjusted for age and hormone receptor status.

Results 49 of the 4061 patients in the PRAEGNANT registry met the requirements for this analysis. Median age was 56 (IQR 48-64) years and 87.8% of the patients were hormone receptor positive. At baseline 15 patients were HER2-negative and 34 patients were HER2-positive. Within a median observation time of 9 months (95%CI: 3.8, 23.7) 35 PFS events occurred. Initially HER2 positive patients had a longer PFS (HR=0.49, 95% CI (0.24, 1.03), p=0.07) compared to initially HER2-negative patients. The 1- and 2-year-PFS rates were also higher for patients initially HER2-positive: 1-year-PFS: 52% (95% CI: 36%, 73%) versus 26 % (95% CI: 12%, 52%); 2-year-PFS: 44% (95% CI: 29%, 67%) versus 19% (95% CI: 7%, 50%).

Conclusions Median PFS and 1- and 2-year PFS rate appear better in patients HER2-positive at initial diagnosis receiving standard HER2-directed therapies. Although our result has to be interpreted with caution because of the small cohort and the retrospective nature of our analysis, it justifies prospective research including initially HER2-negative patients switched to HER2-positive as a distinct entity.

Publication History

Article published online:
01 June 2021