Real-World Clinical Outcomes in Biological Subgroups of Breast Cancer in the Hospital District of Southwest Finland.

BACKGROUND: Comparing breast cancer survival trends globally, Finland is among the top three countries in Europe. However, outcome data on breast cancer subgroups in the Finnish population are limited. This retrospective, registry-based study aimed to assess patient characteristics and clinical outcomes of different breast cancer subgroups in early (EBC) and metastatic breast cancer (MBC) in a real-life clinical setting. MATERIALS AND METHODS: The study consisted of 6,977 adult, female patients with breast cancer diagnosed in Southwest Finland during 2005-2018. Patients were divided into four mutually exclusive groups: human epidermal growth factor receptor 2 positive (HER2+), triple negative, HER2-/hormone receptor positive (HR+), and HER2 and/or HR status unknown, and further into patients with EBC and MBC. Overall survival (OS) was assessed as a clinical outcome, as well as the following real-world (rw) clinical outcomes: disease-free survival (rwDFS), progression-free survival (rwPFS), and distant recurrence-free interval (rwDRFI). RESULTS: Within EBC, 5-year survival was the highest (88%) in HER2-/HR+, followed by 85% in HER2+, and 75% in triple negative. The rwDFS varied significantly in EBC (5-year rwDFS HER2 -/HR+, HER2+, triple negative: 87%, 80%, 71% respectively). In MBC, median survival was 2 years for both HER2-/HR+ and HER2+ and markedly shorter for triple negative (0.8 years). Independent predictors of mortality were age (hazard ratio [HR], 1.1), other subgroups than HER2-/HR+ (HR, 1.2-1.9), metastatic disease (HR, 9.8), and other malignancies (HR, 2.7). CONCLUSION: This registry-based study demonstrates significant differences in breast cancer outcomes on the subgroup level, as well as poorer outcomes compared with clinical trials, giving complementary insight on clinical characteristics in an unselected patient population. IMPLICATIONS FOR PRACTICE: This retrospective, registry-based study assessed the clinical outcomes of different breast cancer subgroups in 6,977 adult, female patients with breast cancer diagnosed in Southwest Finland during 2005-2018. Results demonstrated significant variation in the survival between subgroups in both early breast cancer and metastatic breast cancer, as well as differences between unselected patients representing the standard of care and randomized clinical trials. Although, according to the global comparison of survival trends, the net survival of patients with breast cancer in Finland is generally high, there is great variation between subgroups. These real-life breast cancer data provide tools to further evaluate medical need in different breast cancer subgroups.

Gimap3 regulates tissue-specific mitochondrial DNA segregation.

Mitochondrial DNA (mtDNA) sequence variants segregate in mutation and tissue-specific manners, but the mechanisms remain unknown. The segregation pattern of pathogenic mtDNA mutations is a major determinant of the onset and severity of disease. Using a heteroplasmic mouse model, we demonstrate that Gimap3, an outer mitochondrial membrane GTPase, is a critical regulator of this process in leukocytes. Gimap3 is important for T cell development and survival, suggesting that leukocyte survival may be a key factor in the genetic regulation of mtDNA sequence variants and in modulating human mitochondrial diseases.