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The expansion of molecular genetic knowledge leads to targeted therapy which is a common part of cancer treatment. Targeted agents also exist for breast cancer. However, new efficient molecules are urgently needed. On one hand, there are cancer subgroups where we do not have efficient targeted drugs, on the other hand, the results of established cancer therapies can be improved by interfering with another signal transduction pathway. Everolimus is a targeted agent which was effective in several clinical trials and became registered for treatment of hormone receptor positive breast cancer. This article summarizes the results of published breast cancer everolimus trials. The results of two phase 3 trials are available. In the BOLERO-2 trial exemestane was compared with the combination of exemestane and everolimus, while in BOLERO-3 trial trastuzumab and vinorelbine were investigated with or without everolimus. In both trials the progression-free survival was significantly longer in the experimental arm. The overall survival data of BOLERO-2 trial, a secondary end point, are also available. The 4.4 month benefit in the experimental arm is clinically important but it has not reached the level of statistical significance. We have not had biomarkers so far that could help us to identify a subgroup of cancers sensitive to everolimus.

Over the past decade, significant progress has been made in the management of rectal cancer. Advances in surgical technique and adjuvant therapies have led to significant improvements in outcome for some patients. The advances in preoperative therapies have led to the need for an accurate preoperative staging technique to select those patients who are expected to benefit from these interventions without subjecting others to unnecessary treatment. Performing neoadjuvant therapy knowledge of the relationship of the tumor to the circumferential resection margin is of importance. In Hungary, respecting European guidelines, the high resolution magnetic resonance imaging is mandatory in the staging of rectal cancer, and in early rectal cancer transrectal endosonography has a complementary role. The current role of multidetector computer tomography is for detecting distant metastasis and in local tumor staging of advanced cancers.

Positron emission tomography (PET) has revolutionized the diagnostic opportunities of malignances, however, it has still a controversial role at some conditions in the management of breast cancer. The article compares PET alone and PET/CT. We review the latest trends of using PET or PET/CT for diagnosis, staging, evaluation of the primary tumor and regional lymph node status, as well as early detection of recurrence and distant lesions. PET/CT provides new methods of assessment of early chemo/endocrine therapy response of locally advanced breast cancer. We discuss the development of new radiotracers and their value in predicting treatment response, identifying tumor subtypes and finding new therapeutic targets by them.

The indication of neoadjuvant chemotherapy has been recently extended; it is now applied not only in locally advanced breast cancer but in primarily resecable tumours as well, in order to promote breast conservation. Based on recent clinical results, the reconsideration of traditional lymph node dissection in axillary staging is timely in patients receiving neoadjuvant chemotherapy. Precise axillary staging needs surgical removal of lymph nodes. Based on prospective randomised trials, sentinel lymph node biopsy appears to be appropriate for axillary staging even in tumours requiring neoadjuvant treatment. The extended indication of sentinel lymph node biopsy raises several questions and problems. In the present paper the authors review the results and possible limitations of sentinel lymph node biopsy in relation to neoadjuvant chemotherapy.

Breast screening programs along with advances in diagnostic methods and oncologic treatment have resulted in full recovery for a decisive number of patients diagnosed with early-stage breast cancer. The results of the ultra-radical-, followed by the breast conserving era pose new opportunities and challenges for the oncologic breast surgeon. The focus of oncoplastic surgery is not only on the tumor, but also on the female patient, allowing for individualized immediate breast reconstruction with acceptable esthetic result following radical tumor exstirpation. Modern procedures differ both in concept and technique from that of traditional breast surgery. This paper provides a comprehensive and detailed overview of reconstructive and oncoplastic breast surgery.

Breast cancer is one of the most common malignancies in women. Approximately 15% of cases belong to the triple-negative breast cancer (TNBC) group, in which no estrogen/progesterone receptors, or HER2 expression is detected. The unfavorable prognosis of this group of patients, as well as the lack of effective targeted therapy makes TNBC the subject of intensive research. In the present study, we searched PubMed for publications from January 2007 to June 2009 with the following key-words in addition to "breast cancer" and "triple negative": "epidemiology" or "gene-profile" or "predictive" or "prognostic" or "therapy" or "review". A total of 513 publications were identified. Relevant references were also reviewed. Beyond the well-known facts that TNBC affects younger patients, and is more common among Afro- or Hispano-Americans with lower socioeconomic status, hormonal environment and obesity emerged as potential etiologic factors. TNBC is not a homogenous disease. It can be further sub-classified based on histomorphologic features and immunohistochemistry. Hereditary BRCA1 mutations as well as acquired BRCA1 disfunction are described to be common in TNBC. Previously, many investigators considered TNBC to be identical to a subgroup called basal-like breast cancer defined by gene expression micro-array technology, but in the light of more recent findings, this view is no longer accepted by most investigators. Several large studies provide evidence that triple negativity, per se, is an independent adverse prognostic factor, in spite of the fact that approximately 10% of TNBC patients have a good prognosis. The therapy of choice for TNBC is systemic chemotherapy. Promising novel targeted chemotherapeutic agents include PARP1 inhibitors, a new group of compounds exploiting the defective DNA repair machinery. Rubovszky G, Udvarhelyi N, Horváth Z, Láng I, Kásler M. Triple negative breast carcinoma - rewiev of current literature.

During the carcinogenesis of colorectal cancer in about half of the cases K-RAS, while much less frequently B-RAF mutation occur in early adenomas. While K-RAS mutant tumors are more likely present in male patients, B-RAF mutant tumors develop more frequently in females and are independent of the microsatellite status. Colorectal cancers are characterized by EGFR expression; the gene is not mutated, rarely amplified and increased copy number is due to chromosomal polysomy. This phenotype/genotype of colorectal cancer lent support to the introduction of anti-EGFR antibody therapies. For a while positive EGFR expression status of the tumor was the basis of patient selection for these targeted therapies in colorectal cancer. Monotherapies with the two available anti-EGFR antibodies of chemoresistant colorectal cancers resulted in appr. 10% objective response rate, which was independent of the level of EGFR expression. In case of panitumumab it was discovered that the efficacy of this targeted therapy depends on the K-RAS mutant status of the tumors. Furthermore, preliminary data suggest that cetuximab combined with chemotherapy is effective also exclusively in K-RAS wild-type tumors. Based on these data it is safe to say that K-RAS mutant status of colorectal cancer is a negative predictor for EGFR-targeted therapies of colorectal cancer. Accordingly, it is necessary to determine the K-RAS status of colorectal cancer before making therapeutic decisions.

Renal function aberrations during bisphosphonate treatment is a well-known phenomenon. In our retrospective study we examined renal functions of 97 breast cancer patients with bone metastasis during their first year of bisphosphonate treatment i.e. (1) frequency of initial renal function alterations; (2) frequency of decreasing renal function during bisphosphonate treatment; (3) the connection between the laboratory findings and the renal function parameters measured at the beginning of bisphosphonate treatment. At the beginning of bisphosphonate treatment we found a surprisingly high rate (26.80%) of decreased creatinine clearance calculated by the Cockcroft-Gault formula. Decreased creatinine clearance at least once during bisphosphonate treatment has been found in 32.99% of the patients, and in 13.4% of the patients with decreased renal function parameters before bisphosphonates it remained decreased during the one-year period. Expected normal renal function is prognosticated by the renal function parameters and serum calcium level measured before starting bisphosphonate treatment. However, we could not demonstrate any connection between decreasing renal function and either the route of administration or the generation or type of bisphosphonates or the previous use of platinum compounds. Our analysis confirms the necessity of monitoring renal function before and during bisphosphonate treatment, and it is advisable to calculate the creatinine clearance in the upper quarter of the normal range of creatinine levels. In case of decreased renal function, change to a less nephrotoxic bisphosphonate or discontinuing the treatment is suggested. While our results are at variance with the published literature, the above-mentioned questions should be examined in a prospective trial.

The prognosis of HER-2-positive breast cancer (characterized by amplification of the HER-2 oncogene and/or overexpression of HER-2 receptor) is unfavourable. Trastuzumab (Herceptin), a monoclonal antibody against HER-2 receptor can improve the outcome of HER-2-positive breast cancer. Up to now this was proven only in advanced disease. Recently five large multicentric phase III adjuvant trials gave level one evidence on the benefit of adjuvant treatment with Herceptin, concerning disease-free survival (DFS) and overall survival (OS). Herceptin has decreased the relative risk of recurrence with about 50% and that of death with nearly 30% in HER-2-positive early breast cancer. Based on these results Herceptin, together with chemotherapy, has been recently approved for the adjuvant treatment of HER-2-positive breast cancer.

New results presented at ASCO Conference in 2003 added further important data to our knowledge on successful use of irinotecan in colorectal cancer (CRC). Irinotecan - just like oxaliplatin - given as neoadjuvant therapy with 5-FU - folinic acid (FUFA) can render originally unresectable liver or lung metastases of CRC resectable, giving the hope of long-term survival for a proportion of patients. Irinotecan combined with 5-FU is an essential part of the most successful palliative sequential chemotherapy of stage IV CRC. Sequential FOLFIRI before or after FOLFOX combination ensures the longest possible progression-free and overall survival for metastatic CRC patients in the palliative setting. In order to achieve the longest survival time, sequential use of both 5-FU, irinotecan and oxaliplatin is necessary. The French GERCOR Group achieved 26 months median overall survival with the sequential use of continuous infusional FUFA, oxaliplatin and irinotecan combinations in stage IV CRC. The analysis of large phase III trials using 5-FU, irinotecan and oxaliplatin revealed that the higher proportion of patients was treated with all three drugs, the longer overall survival was achieved. If applied with caution, toxicity and efficacy of irinotecan in elderly patients is not significantly different from that seen in younger population. The anti-VEGF bevacizumab increases the efficacy of first-line irinotecan therapy, while the addition of cetuximab restores irinotecan sensitivity in second line treatment of stage IV CRC. The combination of irinotecan with oral capecitabine is safe and effective in advanced CRC.

The authors investigated the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in 101 metastatic colorectal cancer patients treated with 5-fluoropyrimidine-based therapy and in 196 healthy individuals by PCR-RFLP method. There was no significant difference in genotype distribution of patients and healthy controls, and between subgroups investigated according to clinical parameters (age, gender, tumor location, grade and treatment type). However, after a 3-30 (median 18.5) months follow-up the survival of patients with T allele proved to be better than that of patients with wild type (CC) genotype (p=0.036). In case of CT and TT genotypes the survival of patients receiving only first line therapy was significantly shorter than that of patients receiving more lines of treatment (p=0.015). Determination of MTHFR C677T polymorphism has prognostic value in case of patients with metastatic colorectal cancer receiving 5-fluoropyrimidine-based therapy, and may help in designing the individual (group) tailored therapy.

Aim: The authors present the Hungarian interim analysis and experience with the BCIRG 001 randomized, multicentric, phase III clinical trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) and FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer patients. The results are presented according to international data., Patients and Methods: Three Hungarian centers - St. Margit Hospital, Budapest, National Institute of Oncology, Budapest, Petz Aladár Hospital, Gyôr - participated in the international trial. Between June 1997 and June 1999, 61 patients with node positive breast cancer were enrolled in the study after the surgery. Thirty-four patients were randomized to TAC (75/50/500 mg/m2 6x q3wk) and 27 patients were randomized to FAC (500/50/500 mg/m2 6x q3wk) chemotherapy, with prospective stratification by node (1-3, 4+). In the case of patients with ER and/or PR positive tumours 5 years tamoxifen treatment was started. Radiotherapy was performed after the 6th cycle of chemotherapy., Results: 36 months of follow up was performed. In both arms the hematological toxicity was more frequent. The TAC group showed a higher incidence of neutropenia (76%) compared to the FAC (22%), as well as a higher incidence of febrile neutropenia (26%), without grade 3-4 infection and there were no cases of septic death. Regarding non-hematological toxicity more grade 3-4 nausea and vomiting was observed in the FAC group. At three years follow up, the international results show statistically significant improvement in disease-free survival (82% vs. 74%, p=0.0011) in favour of TAC, and similar tendency was observed in the case of overall survival (92% vs. 87%, p=0.11). This benefit with TAC was seen regardless of hormone receptor status. Due to the low number of Hungarian patients we cannot declare the same results., Conclusions: Based on the international analysis TAC was superior to FAC chemotherapy. Additional follow up data will evaluate the role of TAC in the adjuvant setting of early breast cancer treatment. The results indicate that TAC has the potential to be incorporated in the new strategies of adjuvant breast cancer treatments.

Taxol (paclitaxel) and Herceptin (trastuzumab) are two milestones in the treatment of metastatic breast cancer. Accordingly it was feasible to study the combination of these two highly active drugs (with different toxicity profiles and mechanisms of action) in the treatment of metastatic breast cancer. In multicentric phase III trial performed in the US the combination of Herceptin with either taxane or anthracyclin was investigated. It was established that the combination of Herceptin with Taxol treatment significantly improves the overall response rate, increases the time to progression and the overall survival. These effects are more pronounced in patients characterized with HER/2 +++ overexpression. Based on these evidences the Herceptin-Taxol combined treatment protocol was introduced in Hungary for the treatment of Stage IV breast cancer patients.