Real-World Observational Study of Incidence and Outcomes in an HR+/HER2– Early Breast Cancer Population with High-Risk of Recurrence in Finland

Real-world data on patients with early breast cancer (EBC) with high-risk features remains limited. This population-based study determined the incidence, outcomes and characteristics of patients with hormone receptor (HR)-positive, human epidermal growth factor 2 receptor (HER2)-negative EBC with high-risk features treated in everyday clinical care in two Finnish hospital districts which represent approximately 40% (2.5 million) of the total Finnish population (5.5 million). Adult female patients with BC (ICD-10 C50*) diagnosed between January 2012–June 2019 were indexed at the first BC diagnosis and followed until December 2019 or death. EBC was defined as having no records of metastasis within 90 days of index. High-risk status was defined as ≥ 4 positive axillary lymph nodes (ALNs) or 1–3 ALNs with either grade 3 tumor or tumor size ≥ 5 cm. Outcomes included invasive disease-free survival (IDFS), distant relapse-free survival (DRFS) and overall survival (OS) and were assessed using Kaplan-Meier methods and Cox regression models. Among the 8678 patients with HR+/HER2– EBC, risk classification was feasible in 8081 (93.1%) individuals. Of these, 1407 (17.4%) were defined as high-risk and the remaining 6674 (82.6%) as low-risk patients. The average annual incidence of high-risk HR+/HER2– EBC in 2012–2018 was 21.8/100,000 women. Five-year invasive disease-free survival (IDFS) and distant recurrence-free survival (DRFS) showed higher risk of recurrence for the high-risk group: IDFS 79.7% (95% CI 77.0–82.2) vs 89.3% (88.3–90.2) in the low-risk group; DRFS 82.4% (79.7–84.7) vs 92.9% (92.1–93.7) in the low-risk. Five-year overall survival (OS) in the high-risk group was 89.5% (87.3–91.4) and was 95.4% (94.7–96.0) in the low-risk group. This study showed that high-risk patients account for 17% of newly diagnosed HR+/HER2– EBC in Finland. The high-risk profile was associated with increased risk of recurrence, distant relapse and death compared to low-risk patients. The poorer outcomes of high-risk HR+/HER2– EBC emphasizes a clear unmet need in improving the identification and treatment of these patients. The most common breast cancer type is hormone receptor (HR)-positive, human epidermal growth factor 2 receptor (HER2)-negative breast cancer, which means that the cancer cells have HR but not HER2 on their surface. Some patients with HR-positive, HER2-negative breast cancer diagnosed in early stage may experience a cancer recurrence despite use of standard adjuvant (i.e., post-surgical) treatment. It is known that high-grade cancer (high aggressivity of tumor cells), high number of affected lymph nodes in the armpit and large tumor size are associated with the risk of breast cancer-related death. A recent clinical trial, called monarchE, utilized a combination of these criteria to define a high-risk early breast cancer patient and showed that the high-risk HR-positive, HER2-negative early breast cancer patients may benefit from a combination of abemaciclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, and endocrine therapy. However, there are limited data on the occurrence and recurrence rate of this high-risk group in the real world. This study determined the incidence, specific clinical features and risk of cancer recurrence in HR-positive, HER2-negative early breast cancer patients with monarchE high-risk features treated in routine clinical care in Finland. These high-risk patients account for 17% of newly diagnosed HR-positive, HER2-negative early breast cancer in Finland. Moreover, the high-risk patients had on average a 3.8-fold risk of experiencing a distant cancer recurrence beyond breast and nearby lymph nodes compared to patients who did not have the monarchE high-risk features, and they displayed reduced survival. The consistently poor outcomes among the high-risk patients emphasize an unmet need in identifying improved treatments for these patients.