Objective—The goal of this study was to search for an association between a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) levels and the occurrence of preeclampsia, its characteristics (time-onset and severity), and its consequences (occurrence of fetal growth restriction or preterm delivery). Methods and Results—We studied 140 pairs of women in a case-control study with 3 matching criteria: maternal age, gestational age, and ethnic origin. We measured ADAMTS13 activity using a fluorescence resonance energy transfer assay with the fluorescence resonance energy transfer-VWF73 peptide. ELISA was used to assess protein antigen levels: ADAMTS13, von Willebrand Factor (VWF), interleukin-6, C-reactive protein, P-selectin, and thrombospondin-1. The lowest levels of ADAMTS13 (activity ≤70% or antigen ≤592 ng/mL) were significantly associated with preeclampsia (odds ratios [OR] [95% confidence interval] of 4.2 [1.1 to 15] and 14.3 [1.7 to 123], respectively). This association was independent of VWF levels and preeclampsia risk factors but dependent on interleukin-6 and C-reactive protein levels for ADAMTS13 activity. Levels of ADAMTS13 activity (≤57%) were significantly associated with early-onset preeclampsia (OR=2.5 [1.1 to 5.8]). Severe preeclampsia was associated with the highest levels of P-selectin (>57 ng/mL) (OR=3.4 [1.2 to 9.7]). Conclusion—Preeclampsia is associated with decreased levels of ADAMTS13, independently of VWF. This decrease is quantitative, occurs early, and seems to be dependent on inflammation. Our results suggest that ADAMTS13 could participate in the pathophysiology of preeclampsia.

Importance: Brain metastases portend poor prognosis in patients with metastatic breast cancer (MBC). Designing treatment and prevention clinical trials requires knowledge of brain metastases incidence with each line of therapy. Objectives: We assessed the prevalence and cumulative incidence of brain metastases in a large MBC patient cohort by subtype and line of therapy, and the impact of HER2-low expression on prevalence. Design, Setting and Outcomes: We analyzed brain metastases prevalence in patients with MBC in a nationwide electronic health record-derived de-identified database. The primary outcome was first diagnosis of brain metastases. We estimated prevalence and incidence of brain metastases by MBC subtype, including HER2-low and therapy line. We used the cumulative incidence function to estimate brain metastases risk in patients without brain metastases at initiation of systemic therapy. All P-values are 2-sided, and a P-value ≤.05 indicates statistical significance. Results: Among 18 075 patients with MBC, 1102 (6.1%) had at least 1 brain metastasis at first-line therapy initiation. For the remaining 16 973 patients, cumulative incidence of brain metastases at 60 months was 10% in patients with hormone receptor-positive (HR+)/HER2− disease, 23% for HR+/HER2+ disease, 34% for HR−/HER2+ disease, and 22% for triple-negative breast cancer (TNBC). HER2-low expression within HR+/HER2− and TNBC subtypes had no impact on brain metastases incidence. Brain metastases prevalence increased per line of therapy for patients with all breast cancer subtypes. Conclusions: Brain metastases incidence increases per line of therapy for every MBC subtype. The HER2-low biomarker does not impact brain metastases incidence within historical subtypes.

Real-world studies have suggested decreased trastuzumab emtansine (T-DM1) effectiveness in patients with metastatic breast cancer (mBC) who received prior trastuzumab plus pertuzumab (H + P). However, these studies may have been biased toward pertuzumab-experienced patients with more aggressive disease. Using an electronic health record-derived database, patients diagnosed with mBC on/after 1 January 2011 who initiated T-DM1 in any treatment line (primary cohort) or who initiated second-line T-DM1 following first-line H ± P (secondary cohort) from 22 February 2013 to 31 December 2019 were included. The primary outcome was time from index date to next treatment or death (TTNT). In the primary cohort (n = 757), the percentage of patients with prior P increased from 37% to 73% across the study period, while population characteristics and treatment effectiveness measures were generally stable. Among P-experienced patients from the secondary cohort (n = 246), median time from mBC diagnosis to T-DM1 initiation increased from 10 to 14 months (2013–2019), and median TTNT increased from 4.4 to 10.2 months (2013–2018). Over time, prior H + P prevalence significantly increased with no observable impact on T-DM1 effectiveness. Drug approval timing should be considered when assessing treatment effectiveness within a sequence.