Predictors of long-term durable response in de novo HER2-positive metastatic breast cancer and the real-world treatment experience at two institutions

Purpose: HER2-directed therapies enable some patients with de novo HER2+ metastatic breast cancer (MBC) to achieve long-term, durable responses (DR). Expert opinion dictates indefinite HER2-directed therapies for patients who achieve DRs, but real-world examples of this practice are lacking in the literature. Patient factors that predict DR continue to be elucidated. Methods: This is a retrospective study of patients with de novo HER2 + MBC. DR is defined as absence of progression/death at any point after diagnosis. Controls are patients with evidence of progression/death. Age, ER/PR status, sites of metastasis, surgical resection of primary tumor, and initial treatment were analyzed. Results: 96 patients with de novo HER2 + MBC, 28 with DR, and 68 with progression were identified. 75% of patients with DR had a single metastatic site, compared with 47% of patients with progression (OR 3.7, p = 0.01). 64% of patients with DR received a regimen containing trastuzumab, pertuzumab, and a taxane, while 28% of patients who progressed did (OR 4.5, p < 0.001). 57% of patients with DR underwent surgical removal of breast primary, compared with 24% of patients who progressed (OR 4.3, p = 0.002.) Among patients with DR, nine patients have been receiving trastuzumab for over ten years with no evidence of disease and one patient opted to discontinue trastuzumab. Conclusion: Nearly a third of patients with de novo HER2 + MBC achieved DR. Factors that correlate with DR include single metastatic site, initial trastuzumab, pertuzumab and taxane therapy, and surgical resection of primary tumor. Among patients with DR, indefinite trastuzumab administration is the norm.