BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.
Triple-positive breast cancer (TPBC), i.e. HER2-positive (HER2+) and hormone receptors-positive breast cancer, is a specific subgroup of breast cancers. TPBC biology is characterized by strong mutual interactions between signaling pathways stimulated by estrogens and HER2 amplification. The present study aims to carry out a population-based analysis of treatment outcomes in a cohort of hormone receptor (HR) positive and negative breast cancer patients who were treated with anti-HER2 therapy in the Czech Republic. The BREAST research database was used as the data source for this retrospective analysis. The database covers approximately 95% of breast cancer patients treated with targeted therapies in the Czech Republic. The analysis included 6,122 HER2-positive patients. The patients were divided into two groups, based on estrogen receptor (ER) or progesterone receptor (PR) positivity: hormone receptor negative (HR-) patients had both ER- and PR-negative tumors (n=2,518), unlike positive (HR+) patients (n=3,604). HR+ patients were more often diagnosed premenopausal at the time of diagnosis, presented more often at stage I or II and their tumors were less commonly poorly differentiated. The overall survival (OS) was significantly higher in subgroups of HR+ patients according to treatment setting. When evaluated by stages, significantly higher OS was observed in HR+ patients diagnosed at stages II, III, and IV and regardless of tumor grade.
- MeSH
- lidé MeSH
- míra přežití MeSH
- nádorové biomarkery MeSH
- nádory prsu * farmakoterapie genetika MeSH
- prognóza MeSH
- receptor erbB-2 antagonisté a inhibitory genetika MeSH
- receptory pro estrogeny genetika MeSH
- receptory progesteronu genetika MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
The paper examines the development and testing of an electro-pneumatic device for wound healing therapy after surgery in the neck area. The device generates air pressure values in a miniaturized cuff using electronic circuitry to drive an electro-valve and air compressor. The device works in two distinct modes: continuous pressure mode and pulsating pressure mode. The pressure value setting can vary from 3 to 11 mmHg, and the pulsating pressure mode's operating frequency range is approximately 0.1 to 0.3 Hz. Laboratory measurements were conducted to evaluate the device's correct functioning in both continuous and pulsating pressure modes. A four-day prospective study with animals (n = 10) was also conducted to evaluate neck wound healing therapy using the electro-pneumatic device. Out of the twelve histological parameters analysed to reveal the differences between the experimental and control wounds, only one demonstrated a significant difference. Out of the ten animals treated with the device, three showed a significant difference in terms of benefit after therapy. We can therefore conclude that the device potentially improves the wound healing process in the neck area if the pre-set air pressure value does not exceed 8 mmHg.
- MeSH
- design vybavení MeSH
- hojení ran * MeSH
- modely nemocí na zvířatech MeSH
- poranění krku etiologie terapie MeSH
- prasata MeSH
- prospektivní studie MeSH
- techniky uzavření rány přístrojové vybavení MeSH
- výsledek terapie MeSH
- zdroje elektrické energie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Owing to their central role in the initiation and regulation of antitumor immunity, dendritic cells (DCs) have been widely tested for use in cancer immunotherapy. Despite several encouraging clinical applications, existing DC-based immunotherapy efforts have yielded inconsistent results. Recent work has identified strategies that may allow for more potent DC-based vaccines, such as the combination with antitumor agents that have the potential to synergistically enhance DC functions. Selected cytotoxic agents may stimulate DCs either by directly promoting their maturation or through the induction of immunogenic tumor cell death. Moreover, they may support DC-induced adaptive immune responses by disrupting tumor-induced immunosuppressive mechanisms via selective depletion or inhibition of regulatory subsets, such as myeloid-derived suppressor cells and/or regulatory T cells (Tregs). Here, we summarize our current knowledge on the capacity of anticancer chemotherapeutics to modulate DC phenotype and functions and the results of ongoing clinical trials evaluating the use of DC-based immunotherapy in combination with chemotherapy in cancer patients.
- MeSH
- dendritické buňky imunologie MeSH
- imunoterapie MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- protinádorové látky terapeutické užití MeSH
- protinádorové vakcíny imunologie MeSH
- vakcinace * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100% agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.
- MeSH
- imunohistochemie metody MeSH
- karcinom patologie MeSH
- laboratorní medicína metody normy MeSH
- lidé MeSH
- metastázy nádorů diagnóza MeSH
- nádorové biomarkery analýza MeSH
- nádory prsu patologie MeSH
- odchylka pozorovatele MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Development of the target therapies of lung cancer was a rapid process which fundamentally changed the pathological diagnosis as well. Furthermore, molecular pathology became essential part of the routine diagnostics of lung cancer. These changes generated several practical problems and in underdeveloped countries or in those with reimbursement problems have been combined with further challenges. The central and eastern region of Europe are characterized by similar problems in this respect which promoted the foundation of NSCLC Working Group to provide up to date protocols or guidelines. This present paper is a summary of the molecular pathology and target therapy guidelines written with the notion that it has to be upgraded continuously according to the development of the field.
- MeSH
- cílená molekulární terapie metody MeSH
- erbB receptory genetika MeSH
- genová přestavba MeSH
- konsensus MeSH
- lidé MeSH
- molekulární patologie metody MeSH
- mutace MeSH
- nádory plic diagnóza farmakoterapie genetika MeSH
- nemalobuněčný karcinom plic diagnóza farmakoterapie genetika MeSH
- protoonkogenní proteiny genetika MeSH
- ras proteiny genetika MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- týmová péče o pacienty MeSH
- tyrosinkinasové receptory genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVES: To retrospectively reclassify the results of fine needle aspiration (FNA) cytology at our institution according to the Bethesda system for reporting thyroid cytopathology (TBSRTC), and to determine whether the introduction of the new classification system would have influenced the diagnostic accuracy compared with our existing system in which suspicious/indeterminate categories (categories III-IV) are managed according to clinical findings and cytopathologists' recommendations. METHODS: FNAs performed under ultrasound guidance between 2001 and 2012, and subsequently verified by histology or repeat FNA and follow-up, were reviewed and retrospectively reclassified according to TBSRTC. RESULTS: Among a total of 1310 histologically verified FNAs, the positive predictive values (%) for malignancy and neoplasia (carcinoma + follicular adenomas) for category I-VI according to the TBSRTC were 5.7/11.3, 2.6/5.5, 14.4/34.2, 23.6/55.0, 57.0/64.5 and 92.2/94.2, respectively. Although all the categories predict malignancy closely, the difference in malignancy rate between categories III and IV was not statistically significant; however, the difference in total neoplasia rate reached statistical significance. When patients with cytological and clinical follow-up were included, the malignancy rated dropped in category I to 2.4%, whereas, in category III, it remained at 13%. Repeat FNA instead of direct surgery spared half of the patients from surgery. The cytopathologists' recommendations for histological verification in category III were associated with an insignificant increase in malignancy rate, but the total neoplasia rate reached 57.5%. CONCLUSIONS: At our institution, the application of the TBSRTC did not improve the diagnostic accuracy for the detection of malignancy compared with current practice. In selected cases with cytological results falling into category III (according to clinical data and cytopathologists' opinions), direct lobectomy seems to be justified.
- MeSH
- cytodiagnostika metody MeSH
- lidé MeSH
- nádory štítné žlázy patologie MeSH
- retrospektivní studie MeSH
- štítná žláza patologie MeSH
- tenkojehlová biopsie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Neoadjuvant chemotherapy (NCT) of breast cancer enabled improved outcomes especially in patients with advanced and inflammatory diseases. Biological heterogeneity of these tumors, however, requires better molecular characterization of the malignant tissue with consequent individualization in the selection of appropriate agents. To date, numerous molecular markers have been identified, and some of them (e.g., measurement of hormonal or growth factors receptors) are already routinely used for breast cancer classification before NCT. In the present article, we summarize current knowledge about established as well as promising biomarkers which have demonstrated prognostic or predictive value in NCT of breast cancer.
- MeSH
- adjuvantní chemoterapie MeSH
- antigen Ki-67 analýza MeSH
- cyklofosfamid terapeutické užití MeSH
- doxorubicin terapeutické užití MeSH
- fluoruracil terapeutické užití MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory prsu farmakoterapie imunologie metabolismus MeSH
- neoadjuvantní terapie * MeSH
- prognóza MeSH
- receptor erbB-2 analýza MeSH
- receptory pro estrogeny analýza MeSH
- receptory progesteronu analýza MeSH
- taxoidy terapeutické užití MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
