Correlation of TROP-2 expression with clinical–pathological characteristics and outcome in triple-negative breast cancer

Abstract Limited data exist regarding the associations between TROP-2 protein expression, clinical–pathological characteristics, and outcome in triple-negative breast cancer (TNBC). TROP-2 expression was determined for patients diagnosed with TNBC between 2000 and 2017 by immunohistochemistry (IHC) (ab227689, Abcam) on whole slide tumor sections, and assessed as continuous and categorical variables (H-score high, 201–300, medium 100–200 and low < 100). We investigated the prognostic value of TROP-2 expression for relapse and survival, associations between TROP-2 expression and baseline patient and tumor characteristics, stromal tumor-infiltrating lymphocytes (sTILs), androgen receptor (AR), standardized mitotic index (SMI) and pathological complete response (pCR, in patients with neoadjuvant chemotherapy) were assessed. We included 685 patients with a median age at diagnosis of 54 years (range 22–90 years). After median follow-up of 9.6 years, 17.5% of patients experienced distant relapse. TROP-2 expression was high, medium and low in 97 (16.5%), 149 (25.3%) and 343 (58.2%) of patients, respectively. The presence of LVI, associated DCIS, nodal involvement, apocrine histology and AR expression were correlated with higher TROP-2 levels. There were no associations between TROP-2 expression and sTILs, time-to-event outcomes, or pCR rate after neoadjuvant chemotherapy. TROP-2 expression is not associated with sTILs level and has no prognostic value in our cohort of stage 1–3 TNBC. However, an association with histotype and AR expression was found, suggesting a histotype specific TROP-2 expression pattern with highest expression in apocrine subtype, warranting further research

Machine Learning Algorithm to Estimate Distant Breast Cancer Recurrence at the Population Level with Administrative Data.

High-quality population-based cancer recurrence data are scarcely available, mainly due to complexity and cost of registration. For the first time in Belgium, we developed a tool to estimate distant recurrence after a breast cancer diagnosis at the population level, based on real-world cancer registration and administrative data. Data on distant cancer recurrence (including progression) from patients diagnosed with breast cancer between 2009-2014 were collected from medical files at 9 Belgian centers to train, test and externally validate an algorithm (i.e., gold standard). Distant recurrence was defined as the occurrence of distant metastases between 120 days and within 10 years after the primary diagnosis, with follow-up until December 31, 2018. Data from the gold standard were linked to population-based data from the Belgian Cancer Registry (BCR) and administrative data sources. Potential features to detect recurrences in administrative data were defined based on expert opinion from breast oncologists, and subsequently selected using bootstrap aggregation. Based on the selected features, classification and regression tree (CART) analysis was performed to construct an algorithm for classifying patients as having a distant recurrence or not. A total of 2507 patients were included of whom 216 had a distant recurrence in the clinical data set. The performance of the algorithm showed sensitivity of 79.5% (95% CI 68.8-87.8%), positive predictive value (PPV) of 79.5% (95% CI 68.8-87.8%), and accuracy of 96.7% (95% CI 95.4-97.7%). The external validation resulted in a sensitivity of 84.1% (95% CI 74.4-91.3%), PPV of 84.1% (95% CI 74.4-91.3%), and an accuracy of 96.8% (95% CI 95.4-97.9%). Our algorithm detected distant breast cancer recurrences with an overall good accuracy of 96.8% for patients with breast cancer, as observed in the first multi-centric external validation exercise

Lateral Wall Dysfunction Signals Onset of Progressive Heart Failure in Left Bundle Branch Block

International audienceOBJECTIVES: This study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT). BACKGROUND: LBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT. METHODS: In 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EF(preserved)), 36% to 49% (EF(mid)), and ≤35% (EF(low)). Sixty-four patients underwent CRT and were re-examined after 6 months. RESULTS: Septal work was successively reduced from controls, through EF(preserved), EF(mid), and EF(low) (all p &lt; 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p &lt; 0.005). In contrast, LV lateral wall work was numerically increased in EF(preserved) and EF(mid) versus controls, and did not significantly correlate with LVEF in these groups. In EF(low,) however, LV lateral wall work was substantially reduced (p &lt; 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p &lt; 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p &lt; 0.005). CONCLUSIONS: In early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT