A tüdőrák molekuláris diagnosztikája

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

Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial

The present analysis, carried out in the context of a randomized phase III trial, confirms superior outcomes for breast cancer patients for whom chemotherapy induces pathological complete response (pCR) after adjusting for other important prognostic factors. In contrast, when tumours do not achieve pCR, patients have a higher risk of relapse. This effect is observed in all intrinsic subtypes and justifies the current interest in post-neoadjuvant trial

The risk of febrile neutropenia in patients with non-small-cell lung cancer treated with docetaxel: a systematic review and meta-analysis

We aimed to assess the incidence of febrile neutropenia in patients with non small cell lung cancer treated with docetaxel as second line chemotherapy by systematic review and meta-analysis of clinical studies. Published studies were retrieved and included if they considered docetaxel at the licensed dose after a previous chemotherapy regimen, and reported the proportion of patients getting FN. Meta-analysis was conducted to estimate the proportion of patients who experience one or more episodes of FN. The pooled, random effects meta-analysis estimate for the proportion of patients who experience one or more episodes of FN on docetaxel was 5.95% (95% CI 4.22–8.31) based on 13 studies, comprising 1609 patients. No significant differences were seen either between studies that permitted the use of prophylactic granulocyte colony-stimulating factors or between phase II and phase III trials

Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

BACKGROUND: One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. METHODS: The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. RESULTS: uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. CONCLUSION: These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients

1st International consensus guidelines for advanced breast cancer (ABC 1)

The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines

Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial.

BACKGROUND: Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. PATIENTS AND METHODS: Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. RESULTS: Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P &lt; 0.001 in favour of pCR], DMFS (HR = 0.32, P &lt; 0.001) and OS (HR = 0.32, P &lt; 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). CONCLUSIONS: pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis. CLINICALTRIALSGOV: EORTC 10994/BIG 1-00 Trial registration number NCT00017095

Use of ER/PR/HER2 subtypes in conjunction with the 2007 St Gallen Consensus Statement for early breast cancer

<p>Abstract</p> <p>Background</p> <p>The 2007 St Gallen international expert consensus statement describes three risk categories and provides recommendations for treatment of early breast cancer. The set of recommendations on how to best treat primary breast cancer is recognized and used by clinicians worldwide. We now examine the variability of five-year survival of the 2007 St Gallen Risk Classifications utilizing the ER/PR/HER2 subtypes.</p> <p>Methods</p> <p>Using the population-based California Cancer Registry, 114,786 incident cases of Stages 1-3 invasive breast cancer diagnosed between 2000 and 2006 were identified. Cases were assigned to Low, Intermediate, or High Risk categories. Five-year-relative survival was computed for the three St Gallen risk categories and for the ER/PR/HER2 subtypes for further differentiation.</p> <p>Results and Discussion</p> <p>There were 9,124 (13%) cases classified as Low Risk, 44,234 (65%) cases as Intermediate Risk, and 14,340 (21%) as High Risk. Within the Intermediate Risk group, 33,735 (76%) were node-negative (Intermediate Risk 2) and 10,499 (24%) were node-positive (Intermediate Risk 3). For the High Risk group, 6,149 (43%) had 1 to 3 positive axillary lymph nodes (High Risk 4) and 8,191 (57%) had four or more positive lymph nodes (High Risk 5).</p> <p>Using five-year relative survival as the principal criterion, we found the following: a) There was very little difference between the Low Risk and Intermediate Risk categories; b) Use of the ER/PR/HER2 subtypes within the Intermediate and High Risk categories separated each into a group with better five-year survival (ER-positive) and a group with worse survival (ER-negative), irrespective of HER2-status; c) The heterogeneity of the High Risk category was most evident when one examined the ER/PR/HER2 subtypes with four or more positive axillary lymph nodes; (d) HER2-positivity did not always translate to worse survival, as noted when one compared the triple positive subtype (ER+/PR+/HER2+) to the triple negative subtype (ER-/PR-/HER2-); and (e) ER-negativity appeared to be a stronger predictor of poor survival than HER2-positivity.</p> <p>Conclusion</p> <p>The use of ER/PR/HER2 subtype highlights the marked heterogeneity of the Intermediate and High Risk categories of the 2007 St Gallen statements. The use of ER/PR/HER2 subtypes and correlation with molecular classification of breast cancer is recommended.</p