Case report: Definitive therapy for local progression in patients with responding metastatic HER2-positive breast cancer

Background The role of definitive locoregional treatment of the primary tumor in de novo metastatic breast cancer (MBC) remains controversial, with randomized trials largely demonstrating no survival benefit. In the era of effective HER2-targeted therapies, isolated progression at the primary tumor site in patients with otherwise well-controlled metastatic disease represents an emerging clinical scenario. Methods We conducted a retrospective case series of patients with HER2-positive MBC treated at our institution between January 2007 and June 2025 who developed isolated clinical local or locoregional progression and underwent definitive local therapy without modification of HER2-targeted systemic therapy. Patient and treatment characteristics were summarized descriptively. Outcomes of interest included duration of continued systemic therapy following local treatment with follow up until January 2026. Results Nine patients were identified. Seven had liver metastases at diagnosis. All patients received taxane-based chemotherapy followed by maintenance trastuzumab with or without pertuzumab; seven achieved complete radiologic response. Six patients experienced local progression and three locoregional progression. Definitive local treatment included mastectomy in seven patients and lumpectomy in two. Three patients received radiotherapy. One surgical specimen contained DCIS only; all other invasive tumors retained HER2 positivity at progression. Following local therapy, patients continued first-line maintenance HER2-targeted treatment for a median of 45 months (range 11-156), including eight ongoing observations at last follow up. At last follow-up, all remained on the same systemic regimen except one who transitioned to TDxd after intracranial progression. Conclusion Continued use of the anti-HER2 backbone after local treatment was observed in this selected case series. Although these observations do not establish a causal benefit of local intervention, they support further studies to define the role of this approach in appropriately selected patients.