Background: Clinical trials have shown mixed results regarding the benefit of metastasis-directed radiation therapy (MDRT) in oligoprogressive (OP) metastatic breast cancer (MBC), leading to ongoing debate about its role. This study aimed to investigate whether MDRT can prolong the duration of systemic therapy for ≥6 months in patients with OP MBC. Methods: This retrospective cohort study included patients with MBC who received MDRT for OP disease between December 2017 and March 2023. Patients who received MDRT to the brain were excluded. Medical records were reviewed through July 2024. The primary endpoint was the proportion of patients remaining on the same systemic therapy for ≥6 months post-MDRT. Results: In total, 52 patients with OP MBC treated with MDRT were included, with 36 (69%) with HR+/HER2- disease, 10 (19%) with HER2+ disease, and 6 (12%) with TNBC. Among the 47 patients with follow-up data available, 28 (60%) remained on their systemic therapy at 6 months, including 65% (22/34) of patients with HR+/HER2- disease, 56% (5/9) with HER2+ disease, and 25% (1/4) with TNBC (p = 0.30). Among the 38 patients with a follow-up time of at least 1 year post-MDRT, 47% (18/38) remained on the same systemic therapy. The median time to next systemic therapy and median PFS were 6.9 months (95% CI, 5.7–14.7) and 6.2 months (95% CI, 4.1–9.7), respectively. Conclusions: Over half of patients with OP MBC remained on the same systemic therapy for at least 6 months following MDRT, which suggests that MDRT may help prolong systemic therapy duration for select patients.

Background/Objectives: The 8th edition of the American Joint Committee on Cancer integrates histology and biomarker status with anatomic extent in breast cancer (BC) pathologic prognostic staging (PPS). However, PPS IB includes anatomic locally advanced hormone-receptor-positive/HER2-negative (LA-HR+/HER2-) and early-stage triple-negative BC (ES-TNBC). Previous research shows that increased nodal involvement is a critical predictor of worse prognosis, raising questions about whether biological subtype or anatomic stage has a greater influence on outcomes in these discordant cases. We hypothesized that overall survival (OS) remains worse for LA-HR+/HER2- BC compared to ES-TNBC, despite both being classified as PPS IB. Methods: Using the National Cancer Database, we identified patients with LA-HR+/HER2- BC (pT3N1 or pT1-3N2, grade 1–2) and ES-TNBC (T1N0, grade 2–3) treated between 2004 and 2017. Patients without complete primary tumor stage, biomarker status, grade, TNM staging, or treated with neoadjuvant therapy were excluded. The primary endpoint was OS. Multivariable Cox regression evaluated OS between LA-HR+/HER2- BC and ES-TNBC. Results: Among 45,818 patients (17,359 LA-HR+/HER2- BC and 28,459 ES-TNBC), LA-HR+/HER2- BC had significantly worse 6-year OS (86.1% vs. 90.4%; HR = 1.63; p < 0.0001). Among patients receiving appropriate therapies, patients with LA-HR+/HER2- BC had 35% relatively higher risk of death (HR = 1.35; 1.24–1.48; p < 0.0001). These results highlight that LA-HR+/HER2- breast cancer has worse survival compared to ES-TNBC, despite both being classified as PPS IB and receiving all appropriate treatments. Conclusions: Anatomic disease extent remains an important factor in patients with discordant AS and PPS. Future iterations of PPS should re-classify LA-HR+/HER2- breast cancer from PPS IB to ensure more accurate prognostic and survival information.