Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).

INTRODUCTION: Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain. MATERIAL AND METHODS: We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment. The primary endpoint was the evaluation of sociodemographic and clinicopathological characteristics of these patients. RESULTS: A total of 114 patients were included (March-July 2020). At diagnosis, most tumours were infiltrating ductal carcinoma (IDC) (93.9 %), grade 2 (56.1 %), and hormone receptor (HR)-positive (79.8 %). Over 75 % of patients had disease in operable clinical stages (T1-3 N0-1). In the neoadjuvant setting, 86.8 % of patients received trastuzumab plus pertuzumab, and 23.6 % achieved radiological complete response. Breast-conserving surgery was performed in 55.8 % of patients. Surgical specimens showed that 89.5 % of patients had IDC, 49.1 % grade 2, 84.1 % HR-positive, and 8.3 % HER2-negative disease. Most patients had RD classified as RCB-II and Miller/Payne grade 3/4. Grade 3 treatment-related adverse events (trAEs) occurred in 5.3 % of patients. No grade 4/5 AEs occurred. Over 95 % of patients were free of invasive-disease during T-DM1 adjuvant treatment. CONCLUSION: The KARMA study describes the characteristics of patients with HER2-positive EBC with RD after NeoT and the real-life management of a T-DM1 adjuvant regimen, which showed a manageable safety profile in line with the KATHERINE trial data.

Biology of the Triple-Negative Breast Cancer: Immunohistochemical, RNA, and DNA Features.

BACKGROUND: The triple-negative breast cancer (TNBC) constitutes a heterogeneous disease with an aggressive behavior and a poor prognosis. A better understanding of its biology is required to identify new biomarkers and improve clinical outcomes. SUMMARY: To date, the definition and classification of TNBC depends on a multiomic approach including immunohistochemistry (IHC), genomic, and transcriptomic features, and the tumor immune landscape. The development of new technologies has allowed us to sequence the whole cancer genome. The Cancer Genome Atlas (TCGA) and next-generation sequencing have led to a greater knowledge of DNA alterations such as TP53 or BRCA mutations, copy number variations, and DNA methylations. In addition, gene expression profiling has allowed to define a molecular intrinsic classification of TNBC based on mRNA. IHC and genomic profiling are also necessary to identify new immune biomarkers such as the presence of tumor-infiltrating lymphocytes and the expression of immune checkpoint molecules. KEY MESSAGES: This review aimed to provide recent knowledge of TNBC biology and classification focused on IHC, transcriptomics, genomic features, and the new immune biomarkers.