Treatment and Prognosis of Male Breast Cancer: A Multicentric, Retrospective Study Over 11 Years in the Czech Republic.

PURPOSE: Male breast cancer (MBC) is a rare, but increasingly common disease, and lacks prospective studies. Collaborative efforts are needed to understand and address MBC, including its prognosis, in different countries. METHODS: We retrospectively reviewed the clinical, histopathological, and molecular-genetic characteristics, treatments, and survival outcomes of MBC diagnosed between 2007 and 2017 in the Czech Republic. Prognostic factors of overall survival (OS), recurrence-free interval (RFi), and breast cancer-specific mortality (BCSM) were analyzed and indirectly compared to international data. RESULTS: We analyzed 256 patients with MBC (median age 66 years), including 12% with de novo metastatic (M1). Of 201 non-metastatic (M0) patients, 6% were <40 years old, 29% had stage I, 55% were cN0, and 54% underwent genetic testing. Overall, 97% of tumors had estrogen receptor expression ≥10%, 61% had high Ki67 index, 40% were high-grade (G3), and 68% were luminal B-like (HER2-negative). Systemic therapies included endocrine therapy (90%) and chemotherapy (53%). Few (5%) patients discontinued adjuvant endocrine therapy for reasons other than disease relapse or death. Patients treated with aromatase inhibitors alone had significantly shorter RFi (P < .001). OS, RFi, and BCSM were associated with disease stage, T stage, N stage, progesterone receptor expression, grade, and Ki67 index. Median OS reached 122 and 42 months in M0 and de novo M1 patients, respectively. CONCLUSION: Due to the rarity of MBC, this study highlights important findings from real clinical practice. Although the number of patients with MBC with unfavorable features was higher in this Czech dataset than in international studies, the prognosis remains consistent with real-world evidence.

Favorable prognostic significance of membranous ß-catenin expression and negative prognostic significance of cytoplasmic ß-catenin expression in pancreatic cancer.

The aim of this study was to investigate the prognostic significance of membranous ß-catenin and cytoplasmic ß-catenin expression in pancreatic cancer patients (pts). One hundred pts with histologically verified exocrine pancreatic ductal adenocarcinoma were retrospectively studied. The membranous ß-catenin, cytoplasmic ß-catenin, and cell nucleus ß-catenin expression were immunohistochemically evaluated. The expression of membranous ß-catenin was <5% in none of the pts, 5-25% in one patient, 26-50% in 2 pts, 51-75% in 14 pts, and >75% in 81 pts. The expression of cytoplasmic ß-catenin was <5% in 34 pts, 5-25% in 42 pts, 26-50% in 18 pts, 51-75% in 3 pts, and >75% in one patient. The expression of ß-catenin in the cell nucleus was negative in all pts. At the time of the last follow-up, 21 pts were alive and 79 pts had died. Median OS was 1.3 (0.4-2.3) years in pts with membranous ß-catenin expression ≤75% and 1.7 (1.3-2.1) years in pts with membranous ß-catenin expression >75% (p=0.045). Median OS was (1.3-2.0) 1.6 years in pts with cytoplasmic ß-catenin expression ≤25% and 0.9 (0.5-1.2) years in pts with cytoplasmic ß-catenin expression >25% (p=0.040). In the univariate Cox proportional hazard models HR (95% CI) was 0.556 (0.311-0.995) in pts with membranous ß-catenin expression >75% (p=0.048) and 2.200 (1.216-3.980) in pts with cytoplasmic ß-catenin expression >25% (p=0.009). The present results indicate a favorable prognostic significance of membranous ß-catenin expression in pancreatic cancer.

Negative prognostic significance of primary cilia, CD8+ tumor infiltrating lymphocytes and PD1+ cells expression in clear cell renal cancer.

PURPOSE: The aim of this study was to investigate the potential association and combined prognostic significance of the frequency of primary cilia (PC), programmed cell death protein-1 receptor (PD1) and CD8+ tumor infiltrating lymphocytes (TIL) in patients with clear cell renal cancer (ccRCC). METHODS: The frequency of PC, PD1 expression and the frequency of intratumoral CD8+ TIL were evaluated in 104 ccRCC patients. RESULTS: The median frequency of PC was 0.003. The expression of PD1+ cells were <5% in 52 patients, 5-25% in 34 patients and 26-50% in 13 patients and >50% in 5 patients. Intratumoral CD8+ TIL were evaluable in all patients: negative in 1 patient, <25% in 63, 26-50% in 29 and >50% in 11 patients. Overall survival (OS) according to the frequency of PC was significantly shorter in patients with higher frequency (≥0.002) than in patients with lower frequency (<0.002) (p<0.001). Median OS was significantly shorter in patients with higher (25%) CD8+ TIL and higher (>25%) PD1+ expression than in patients with lower (<25%) expression (4.6 vs. 97. years, p=0.006 and 2.9 vs. 8.9 years, p=0.006, respectively). CONCLUSIONS: The present study provides the first data on the potential association and combined prognostic significance of frequency of PC, PD1+ cells and CD8+ TIL in patients with clear cell renal cancer.

Motor correlates of models of secondary bilateral synchrony and multiple epileptic foci.

Bilateral synchronous epileptiform discharges registered in patients with partial epilepsies may be generated by different pathophysiological mechanisms. Differentiation between underlying mechanisms is often crucial for correct diagnosis and adequate treatment in clinical epileptology. The aim of this study was to model in rats two possible mechanisms--secondary bilateral sychrony and interaction between multiple epilepic foci. Furthermore, to describe in detail semiology, laterality and differences in motor phenomena. Secondary bilateral synchrony was modeled by unilateral topical application of bicuculline methiodide (BMI) over the sensorimotor cortex. Bilateral symmetric application of BMI was used as a model of multiple epileptic foci. Electrographic and behavioural phenomena were recorded for 1h following the application of BMI. Electroencephalogram in both groups was characterized by presence of bilateral synchronous discharges. Myoclonic and clonic seizures involving forelimb and head muscles represented the most common motor seizure pattern in both groups. Significant differences were found in the laterality of motor phenomena. Motor seizures in unilateral foci always started in the contralateral limbs whereas symmetrical foci exhibited bilateral independent onset of convulsions. Similar lateralization was observed in interictal motor phenomena (myoclonic jerks). An important influence of posture on epileptic motor phenomena was demonstrated. Active or passive changes in animal posture (verticalization to bipedal posture) caused conversion from unilateral myoclonic jerks or clonic seizures to bilaterally synchronous (generalized) motor phenomena in both groups.