Real-world perioperative treatment patterns and economic burden of recurrence in early-stage HER2-negative breast cancer: a SEER-Medicare study

Aim: This study aimed to describe treatment patterns and quantify the economic impact of recurrence in early-stage human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC).

Materials & methods: Medicare beneficiaries with stages I-III HER2-negative BC and lumpectomy or partial/total mastectomy were identified from SEER-Medicare data (2010-2019). Perioperative therapies were reported in the neoadjuvant and adjuvant setting. Locoregional recurrence and distant metastasis were identified using a claims-based algorithm developed with clinical input and consisting of a diagnosis-based and treatment-based indicator. All-cause and BC-related healthcare resource utilization (HRU) per-patient-month and monthly healthcare costs were estimated from the recurrence date for patients with recurrence and from an imputed index date for patients without recurrence using frequency matching. HRU and costs were compared between groups stratified by hormone receptor-positive (HR+) or triple negative BC (TNBC) using multivariable regression models.

Results: Of 28,655 patients, 8.5% experienced recurrence, 90.4% had HR+ disease, and 5.6% received neoadjuvant therapy. Relative to patients without recurrence, patients with recurrence had more advanced disease (stage II/III: 73.7% vs. 34.0%) and higher-grade tumors (Grade 3/4: 40.6% vs. 18.0%) at diagnosis. Recurrence in HR+/HER2-negative BC and TNBC was associated with higher rates of all-cause hospitalizations (incidence rate ratio [IRR]: 2.84 and 3.65), emergency department (ED) visits (IRR: 1.75 and 2.00), and outpatient visits (IRR: 1.46 and 1.55; all p < 0.001). Similarly, recurrence was associated with higher rates of BC-related HRU, particularly for ED visits in HR+/HER2-negative BC (IRR: 4.24; p < 0.001) and hospitalizations in TNBC (IRR: 11.71; p < 0.001). Patients with HR+/HER2-negative BC and TNBC recurrence incurred higher monthly all-cause (cost difference [CD]: $3988 and $4651) and BC-related healthcare costs (CD: $3743 and $5819).

Conclusions: Our findings highlight the considerable economic burden of recurrence in early-stage HER2-negative BC and underscore the unmet need for optimization of therapies that reduce recurrence in this population.