Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry.

BACKGROUND: About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC). PATIENTS AND METHODS: The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included. RESULTS: As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74-1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68-1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients. CONCLUSION: Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.

Long-term follow-up after successful treatment of vaccine-induced prothrombotic immune thrombocytopenia.

BACKGROUND: Cases of ChAdOx1 nCoV-19 (AstraZeneca) vaccinated patients with thrombocytopenia, elevated D-dimer, and elevated platelet factor 4 (PF4) antibody levels with- and without thrombosis have been reported. No recommendations regarding the duration of anticoagulation have been made, because data on the long-term course beyond the first weeks is lacking. OBJECTIVE: To report on the treatment, medical course, and longitudinal follow-up of laboratory parameters in patients with vaccine-induced prothrombotic immune thrombocytopenia (VIPIT). PATIENTS: We followed VIPIT patients with- (n = 3) and without (n = 3) venous thromboembolism fulfilling the aforementioned laboratory criteria. RESULTS: Elevated D-dimer (median: 35.10 µg/ml, range: 17.80-52.70), thrombocytopenia (42 G/l, 20-101), and strong positivity in the platelet factor 4 (PF4)/heparin-enzyme-immunoassay (2.42 optical density [OD], 2.06-3.13; reference range < 0.50) were present in all patients after vaccination (10 days, 7-17). Routine laboratory parameters rapidly improved upon initiation of treatment (comprising therapeutic non-heparin anticoagulation in all patients and high dose immunoglobulins ± corticosteroids in 5 patients). PF4 antibody levels slowly decreased over several weeks. Patients were discharged in good physical health (8 days, 5-13). VIPIT did not recur during follow-up (12 weeks, 8-17). Five of 6 patients fully recovered (in 2 patients thrombosis had resolved, in 1 patient exertional dyspnea persisted). CONCLUSIONS: Remissions without sequelae can be achieved upon rapid initiation of treatment in patients with VIPIT. Platelet factor 4 antibody levels slowly decreased over several weeks but VIPIT did not recur in any of our patients. Continuation of anticoagulation in VIPIT patients at least until PF4 antibody negativity is reached seems reasonable.