Exceptional responses to systemic treatment in metastatic breast cancer: clinical features and long-term outcomes

Interest in metastatic solid tumors patients achieving exceptionally durable responses to systemic treatment is progressively increasing; however, available evidence still remains limited. This study characterizes patients with metastatic breast cancer (mBC) achieving an exceptional response, with a focus on patients discontinuing systemic treatment.

In this retrospective monocentric study, patients with mBC achieving exceptional responses (2021-2023) were identified; clinical features, hormone receptor (HR) and HER2 status, and radiological responses were collected. Exceptional response was defined as complete (CR) or partial response (PR) lasting for more than twice the expected progression-free survival (PFS). No evidence of disease (NED) was defined as radiological absence of disease achieved integrating locoregional treatments.

We identified 58 exceptional responders: 31 HER2+ (53.5 %), 16 HR+ /HER2- (27.6 %), and 11 HR-/HER2- (19.0 %). 5-year PFS was 89.1 % and 5-year OS was 94.6 % overall, and numerically better in HR-/HER2- mBC (5-year PFS/OS: 100 %) compared to HER2+ (90.2 %/93.5 %) and HR+ /HER2- (80.8 %/93.8 %) mBC. Best radiological response was CR/NED in 69.0 % and PR in 31.0 % of patients. CR/NED status was significantly associated with better outcomes compared to PR (5-year OS: 100 % vs. 83.0 %, p = 0.004). Eleven patients (9 with CR/NED, 2 with PR) discontinued treatment in absence of disease progression; subsequent progression was observed only in one patient with PR.

mBC patients achieving exceptional responses exhibit favorable long-term survival outcomes, particularly if achieving CR/NED. These findings highlight the importance of further research to refine management strategies and explore the potential for systemic treatment discontinuation in these patients.