Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes.

We hypothesized that different BC subtypes are characterized by spatially distinct tumor immune microenvironment (TIME) and that immune gene assembly of metastatic (Met) and non-metastatic (Ctrl) BCs vary across subtypes. Peritumoral, stromal and intratumoral TIL was assessed on 309 BC cases. Hot, cold and immune-excluded groups were defined, and the prognostic role of this classification was assessed.

Prognostic and Clinicopathological Correlations of Cell Cycle Marker Expressions before and after the Primary Systemic Therapy of Breast Cancer.

We aimed to analyze the expression of cell-cycle regulation markers - minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) - in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core biopsy samples obtained prior to neoadjuvant therapy were analyzed. Immunohistochemistry was performed to analyze the expression of MCM2, Ki-67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, the presence of tumor infiltrating lymphocytes (TIL), pathological tumor response rate to the neoadjuvant therapy and patient survival.

Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of residual breast cancer.

Chemotherapeutic agents are often mutagenic. Induction of mutation associated neo-epitopes is one of the mechanisms by which chemotherapy is thought to increase the number of tumor-infiltrating lymphocytes. It is not known, however, whether treatment with various chemotherapeutic agents with different mutagenic capacity induce a significantly different number of stromal tumor-infiltrating lymphocytes (StrTIL) in residual cancer.

Dynamic FDG-PET/CT in the Initial Staging of Primary Breast Cancer: Clinicopathological Correlations.

Our aim was to evaluate correlation between clinicopathological features (clinical T and clinical N stages; histological type; nuclear grade; hormone-receptor and HER2 status, proliferation activity and tumor subtypes) of breast cancer and kinetic parameters measured by staging dynamic FDG-PET/CT examinations. Following ethical approval and patients' informed consent we included 34 patients with 35 primary breast cancers in our prospective study. We performed dynamic PET imaging, and assessed plasma activity noninvasively.

Comparison of different motion correction techniques for dynamic FDG-PET/CT studies in breast cancer patients.

Background: Our aim was to evaluate interchangeability of different motion correction methods in the assessment of dynamic FDG-PET/CT studies in breast cancer patients as well as to assess the interrater reliability of these methods.

Methods: In our prospective study we included patients with malignant breast tumours. Dynamic PET acquisition lasted for 60 minutes after tracer (FDG) injection.

AXL-associated tumor inflammation as a poor prognostic signature in chemotherapy-treated triple-negative breast cancer patients.

A subgroup of triple-negative breast cancer (TNBC) shows epithelial-to-mesenchymal transition (EMT) features, which are sustained by the interaction between cancer cells and tumor-associated macrophages (TAMs). In this study, the clinical relevance of 30 EMT-related kinases and the potential cross-talk with TAMs were investigated in a cohort of 203 TNBC patients treated with adjuvant chemotherapy. The prognostic value of the evaluated markers was validated in two independent cohorts of TNBC patients treated with adjuvant chemotherapy (=95; =137).

Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy.

Background: Studies have partly demonstrated the clinical validity of Ki-67 as a predictive marker in the neoadjuvant setting, but the question of the best cut-off points as well as the importance of this marker as a prognostic factor in partial responder/non-responder groups remains uncertain.

Methods: One hundred twenty patients diagnosed with invasive breast cancer and treated with neoadjuvant chemotherapy (NAC) between 2002 and 2013 were retrospectively recruited to this study. The optimal cut-off value for Ki-67 labeling index (LI) to discriminate response to treatment was assessed by receiver operating characteristic (ROC) curve analysis.

Defining the design space for freeze-dried orodispersible tablets with meloxicam.

Objective: This work focused on simultaneously investigating formulation variables and freeze-drying parameters when preparing orodispersible tablets with meloxicam (Mel), by a Quality by Design (QbD) approach.

Materials And Methods: Methylcellulose (MC) was selected as a matrix forming agent and mannitol (Man) as cryoprotectant, both at two concentration levels. The freezing regime was also varied between fast and shelf-ramped, to find out how it affects the final products.

Morphological and pathological response in primary systemic therapy of patients with breast cancer and the prediction of disease free survival: a single center observational study.

Aim: To identify breast cancer subtypes likely to respond to primary systemic therapy (PST or neoadjuvant therapy) and to assess the accuracy of physical examination (PE) and breast ultrasonography (US) in evaluating and predicting residual size of breast carcinoma following PST.

Methods: 116 patients who received at least two cycles of PST between 1998 and 2009 were selected from a prospectively collected clinical database. Radiological assessment was done by mammography and US.

Expression of cell cycle markers is predictive of the response to primary systemic therapy of locally advanced breast cancer.

We aimed to analyze to what extent expression of four cell cycle regulation markers-minichromosome maintenance protein (MCM2), Ki-67, cyclin A, and phosphohistone-H3 (PHH3)-predict response to primary systemic therapy in terms of pathological complete remission (pCR). In search of an accurate and reproducible scoring method, we compared computer-assisted (CA) and routine visual assessment (VA) of immunoreactivity. We included 57 patients with breast cancer in the study.

Predictive and prognostic value of FDG-PET/CT imaging and different response evaluation criteria after primary systemic therapy of breast cancer.

Objectives: (1) To predict pathological complete remission (pCR) and survival after primary systemic therapy (PST) in patients diagnosed with breast cancer by using two different PET/CT based scores: a simplified PERCIST-based PET/CT score (Method 1) and a combined PET/CT score supplemented with the morphological results of the RECIST system (Method 2) and (2) to assess the effect of different breast carcinoma subtypes on tumor response and its evaluation.

Methods: Eighty-eight patients were enrolled in the study who underwent PET/CT imaging before and after PST. PET/CTs were evaluated by changes in maximum Standardized Uptake Value (SUVmax) and tumor size.

Complexity of Response Evaluation During Primary Systemic Therapy of Breast Cancer: Scoring Systems and Beyond-Preliminary Results.

Background: Precise and standardized response evaluation enables clinicians to tailor primary systemic therapy (PST).

Patients And Methods: Breast cancer patients underwent (18)F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) before and after PST. Response was assessed by maximal Standardized Uptake Value (SUVmax); morphological changes and Ki-67 labeling index (LI).

Response evaluation after primary systemic therapy of Her2 positive breast cancer – an observational cross-sectional study.

Aim: To evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas.; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring.

Methods: 188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled.

Primary systemic therapy for breast cancer: Does the patient's involvement in decision-making create a new future?

Objective: Primary systemic therapy (PST) followed by surgery is the standard initial treatment for locally advanced breast cancer (LABC). However, some patients are averse to mastectomy or breast-conserving surgery and do not consent to these procedures. The reasons for this controversial decision, the factors influencing the decision-making and optimal solutions for decision aiding need to be investigated.

Correlation of the value of 18F-FDG uptake, described by SUVmax, SUVavg, metabolic tumour volume and total lesion glycolysis, to clinicopathological prognostic factors and biological subtypes in breast cancer.

Objective: The aim of this study was to observe the relationships between different metabolic parameters and clinicopathological features (CPFs) or immunohistochemically defined biological subtypes (IHC-BS) in breast cancer.

Materials And Methods: Eighty-two women (83 lesions, tumour size>15 mm) underwent PET/computed tomography imaging after a core biopsy. Maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) in the primary tumour were calculated and compared with CPFs and IHC-BS.

[Monoclonal antibody therapy in breast cancer].

A new trend has been taking place in the daily oncology practice in the past twenty years: we are progressively moving toward individualized and personalized treatments. The treatment of breast cancer is one of the best examples to underline the outstanding effectiveness of the individualized approach. The modern molecular pathology features are capable of predicting the biological behavior of the tumors which gives a new basis for our therapeutic choices, both for neoadjuvant and adjuvant settings, as well as for metastatic disease.

[The role of FDG-PET-CT in the evaluation of primary systemic therapy in breast cancer: links between metabolic and pathological remission].

Introduction: FDG-PET-CT is highly sensitive in detection of viable tumour tissue, giving an importance for that in oncological diagnostics.

Aim: The authors analysed retrospectively the relationship between metabolic response and changes in Ki-67, a proliferation marker.

Methods: Staging FDG-PET-CT scans (before and after therapy) SUVs (Standardized Uptake Value), and morphological changes in the primary tumour and axillary lymph node region were evaluated in 30 patients with breast cancer.