Background Regional lymph node (LN) involvement in colorectal cancer (CRC) identifies the stage and the subset of patients who would benefit from adjuvant chemotherapy. We performed a retrospective analysis to determine if the number of recovered LNs was associated with long-term outcome in patients operated on for stage II and III CRC. Patients and methods Hospital records of 179 patients with CRC followed in our unit from 1997 to April 2003 were reviewed. Results On average 11.68 ± 7.3 LNs were sampled per surgical specimen. Sampling of at least nine LNs appeared to be the minimum number required for accurately predicting LN involvement ( P = 0.002). Three-year rates of disease-free survival (DFS), local recurrence-free survival (LRFS) and overall survival (OS) were lower in patients with fewer than nine LNs sampled ( P = 0.032, P = 0.006 and P = 0.04, respectively). However, this had no impact on the three-year distant metastasis-free survival rate (DMFS) ( P = 0.472). In stage II disease, patients with nine or more LNs dissected had significantly higher three year DFS and LRFS rates than the subgroup with fewer than nine LNs dissected ( P = 0.024 and P = 0.015, respectively), but this did not have any effect on DMFS or OS ( P = 0.406 and P = 0.353, respectively). Conclusion Current protocols provide adjuvant treatment in stage III patients; the problem is to correctly determine stage by recovering as many LNs as possible.

Limburgs Univ Centrum, Diepenbeek, Belgium. Inst Jules Bordet, B-1000 Brussels, Belgium. IDDI, Brussels, Belgium.

Ovarian cancer (OC) is one of the leading causes of cancer-related death in women. In the last decades, a lot of energy and resources have been put into a number of clinical trials, with some success. Nevertheless, the prognosis of patients diagnosed with advanced disease remains extremely poor. As research moved forward, some crucial questions with regard to the optimal upfront management of patients with advanced OC (AOC) have remained unanswered. In this article, we review the rationale behind these controversial issues, and provide the levels of evidence supporting the current recommendations for AOC management.

Background: The impact of aromatase inhibitors (AIs) on non-cancer-related outcomes, which are known to be affected by oestrogens, has become increasingly important in postmenopausal women with hormone-dependent breast cancer. So far, data related to the effect of AIs on lipid profile in postmenopausal women is scarce. This study, as a companion substudy of an EORTC phase II trial (10951), evaluated the impact of exemestane, a steroidal aromatase inactivator, on the lipid profile of postmenopausal metastatic breast cancer (MBC) patients.Patients and methods: The EORTC trial 10951 randomised 122 postmenopausal breast cancer patients to exemestane (E) 25 mg (n = 62) or tamoxifen (T) 20 mg (n = 60) once daily as a first-line treatment in the metastatic setting. Exemestane showed promising results in all the primary efficacy end points of the trial (response rate, clinical benefit rate and response duration), and it was well tolerated with low incidence of serious toxicity. As a secondary end point of this phase 11 trial, serum triglycerides (TRG), high-density lipoprotein cholesterol (HDL). total cholesterol (TC), lipoprotein a (Lip a), and apolipoproteins (Apo) B and A1 were measured at baseline and while on therapy (at 8, 24 and 48 weeks) to assess the impact of exemestane and tamoxifen on serum lipid profiles. Of the 122 randomised patients, those who had baseline and at least one other lipid assessment are included in the present analysis. The patients who received concomitant drugs that could affect lipid profile are included only if these drugs were administered throughout the study treatment. Increase or decrease in lipid parameters within 20% of baseline were considered as non-significant and thus unchanged.Results: Seventy-two patients (36 in both arms) were included in the statistical analysis. The majority of patients had abnormal TC and normal TRG, HDL, Apo A 1, Apo B and Lip a levels at baseline. Neither exemestane nor tamoxifen had adverse effects on TC, HDL, Apo A], Apo B or Lip a levels at 8, 24 and 48 weeks of treatment. Exemestane and tamoxifen had opposite effects on TRG levels: exemestane lowered while tamoxifen increased TRG levels over time. There were too few patients with normal baseline TC and abnormal TRG, HDL, Apo Al, Apo B and Lip a levels to allow for assessment of E's impact on these subsets. The atherocnic risk determined by Apo A I:Apo B and TC:HDL ratios remained unchanged throughout the treatment period in both the E and T arms.Conclusions: Overall, exemestane has no detrimental effect on cholesterol levels and the atherogenic indices, which are well-known risk factors for coronary artery disease. In addition, it has a beneficial effect on TRG levels. These data, coupled with E's excellent efficacy and tolerability, support further exploration of its potential in the metastatic, adjuvant and chemopreventive setting.

Treatment regimens for solid tumours have been extensively investigated for their physical toxic effects, but far less is known about the potential impairment of cognitive function by anticancer treatment regimens. Here, we review published studies that examined cognitive function in adult patients receiving systemic therapy for solid tumours. Our review suggests that patients can experience cognitive changes related to their treatment. However, several studies had methodological limitations, such as use of a limited sample size, lack of baseline assessment, and lack of control for potential confounding factors. Better designed clinical trials are required so that the difficulties patients face in terms of reduced cognitive function as a result of anticancer treatment can be fully elucidated. These trials should have sufficient statistical power and, importantly, should also be prospective.

3170 Background: Several lines of evidence suggest that EGFR, Her-2 and their downstream effectors Akt and MAPK are associated with endocrine resistance in BC. We investigated the expression pattern of these molecules and its relation with duration of response in metastatic BC pts treated with ET. Methods: The expression of EGFR, Her-2, pAkt, pMAPK were evaluated in tumor(tm) specimens from 44 BC pts who were treated with tamoxifen(T) or aromatase inhibitors (AIs) as first-line metastatic therapy. Her-3 and Her-4 were evaluated only in those cases with pAkt or pMAPK expression. The pts were stratified into 2 groups; A:those who progressed early (best response is PD ≤6mo of treatment), B:those who progressed late (PR or SD lasting ≥12 mo). Results: The median age of pts who received T/AIs was 45/55. The median duration of response to T-AIs was 2–3 mo/20–32 mo for pt groups A/B respectively. 22 pts progressed early on T/AIs(n=10/12), while 22 pts progressed late on T/AIs (n=9/13). EGFR,Her-2,pMAPK,pAkt were expressed in 4.5%,9%,37% and11% of tms. All tms with EGFR(n=2) and 4/5 tms with Her-2(n=5) expression were in the pt group A. In those cases with pMAPK(n=16) or pAkt(n=5) expression, Her-4 was the most frequently expressed EGF receptor. In 8/16 tms with pMAPK staining, none of the EGF receptors were expressed, 6/8 pts in this group had late progression on ET. 6/8 pts with tms expressing pMAPK and any of the EGF receptors were in the pt group A. 4/5 pts with pAkt positive tms progressed early on ET. At least one of the EGF receptors was expressed in tms with pAkt expression. Conclusion: Despite being a retrospective analysis with small number of pts, our findings suggest that pAkt expression alone or concurrent expression of both pMAPK and one of the EGF receptors might have some predictive value for sensitivity/duration of response to ET.Our findings need prospective validation in the setting of clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pfizer Novartis

In recent years, strategy in cancer therapy in general, and breast cancer in particular, has been the use of maximum tolerated doses of toxic non-specific agents as well as the investigation of a range of new agents that specifically target tumor-related molecules, in a variety of biological pathways. The trial of chemotherapy (CT) versus chemotherapy+trastuzumab (Herceptin®) in HER-2-overexpressing metastatic breast cancer (MBC) was one of the first to use a biological agent in combination with chemotherapy with success and, together with some trials of taxanes in anthracycline-resistance patients one of the few to demonstrate an overall survival (OS) advantage in MBC. Five main molecular pathways are of particular interest in terms of new drug development in breast cancer: the estrogen receptor (ER) pathway, the tyrosine kinase signal transduction pathway, the cell cycle regulation pathway, the apoptosis pathway and the angiogenesis pathway. This review will focus on new agents, cytotoxic, hormonal and molecular-targeted, which are in advanced clinical stages of development for the treatment of MBC.

PURPOSE The purpose of this study was to register the different cancer cases diagnosed in our hospital with an aim to define the most common and treatable cancer types and help define accurate targets for the allocation of the already limited resources of the Ministry of Health. MATERIALS AND METHODS We surveyed 12 months of the hospital's pathology records to determine the prevalence of various cancer types. RESULTS Out of 9720 biopsy and cytology samples, 662 were cancer cases. Breast and gastric cancers were higher and colorectal cancers were lower than the series reported from the United States. Of the pulmonary malignancies, lung cancer in general was not particularly higher in proportion to other cases, something interesting for a country with smoking rates exceeding 60% of the adult population. Squamous cell lung cancer was more common compared to the rates reported in the western world statistics. CONCLUSION Although biases may exist, as certain cancers are more amenable to surgical intervention and physician groups may have special interest toward a particular cancer, distribution of cancer cases in Turkey is probably similar to the western world.

From the early experience with tamoxifen to the current use of Herceptin, targeted therapy has been proven to be an important part of breast cancer (BC) treatment. In the last decade, advances in molecular biology have allowed scientists to design highly individualized, 'smart' pharmaceuticals, capable of manipulating the growth factor pathways and the genes that are involved in the development and maintenance of the malignant phenotype. The epidermal growth factor receptor (EGFR) family, as one of the best studied growth factor pathways in cancer, resembles a 'treasure island' by providing a wide range of biologically relevant targets involved in breast carcinogenesis. While a large number of new agents targeting this pathway are continuingly being tested in preclinical experiments, clinicians are witnessing the migration of some of these agents to daily practice. The aim of this review is to provide clinicians with an updated synopsis of the most advanced anti-erbB therapeutic strategies with activity against BC.

Liver metastases have long been known to indicate an unfavourable disease course in breast cancer (BC). However, a small subset of patients with liver metastases alone who were treated with pre-taxane chemotherapy regimens was reported to have longer survival compared with patients with liver and metastases at other sites. In the present study, we examined the clinical outcome of breast cancer patients with liver metastases alone in the context of two phase III European Organisation for Research and Treatment of Cancer (EORTC) trials which compared the efficacy of doxorubicin (A) versus paclitaxel (T) (trial 10923) and of AC (cyclophosphamide) versus AT (trial 10961), given as first-line chemotherapy in metastatic BC patients. The median follow-up for the patients with liver metastases was 90.5 months in trial 10923 and 56.6 months in trial 10961. Patients with liver metastases alone comprised 18% of all patients with liver metastases, in both the 10923 and 10961 trials. The median survival of patients with liver metastases alone and liver plus other sites of metastases were 22.7 and 14.2 months (log rank test, P=0.002) in trial 10923 and 27.1 and 16.8 months (log rank test, P=0.19) in trial 10961. The median TTP (time to progression) for patients with liver metastases alone was also longer compared with the liver plus other sites of metastases group in both trials: 10.2 versus 8.8 months (log rank test, P=0.02) in trial 10923 and 8.3 versus 6.7 months (log rank test, P=0.37) in trial 10961. Most patients with liver metastases alone have progression of their disease in their liver again (96 and 60% of patients in trials 10923 and 10961, respectively). Given the high prevalence of breast cancer, improved detection of liver metastases, encouraging survival achieved with currently available cytotoxic agents and the fact that a significant portion of patients with liver metastases alone have progression of their tumour in the liver again, a more aggressive multimodality treatment approach through prospective clinical trials seems worth exploring in this specific subset of women.

Liver metastases have long been known to indicate an unfavourable disease course in breast cancer (BC). However, a small subset of patients with liver metastases alone who were treated with pre-taxane chemotherapy regimens was reported to have longer survival compared with patients with liver and metastases at other sites. In the present study, we examined the clinical outcome of breast cancer patients with liver metastases alone in the context of two phase III European Organisation for Research and Treatment of Cancer (EORTC) trials which compared the efficacy of doxorubicin (A) versus paclitaxel (T) (trial 10923) and of AC (cyclophosphamide) versus AT (trial 10961), given as first-line chemotherapy in metastatic BC patients. The median follow-up for the patients with liver metastases was 90.5 months in trial 10923 and 56.6 months in trial 10961. Patients with liver metastases alone comprised 18% of all patients with liver metastases, in both the 10923 and 10961 trials. The median survival of patients with liver metastases alone and liver plus other sites of metastases were 22.7 and 14.2 months (log rank test, P=0.002) in trial 10923 and 27.1 and 16.8 months (log rank test, P=0.19) in trial 10961. The median TTP (time to progression) for patients with liver metastases alone was also longer compared with the liver plus other sites of metastases group in both trials: 10.2 versus 8.8 months (log rank test, P=0.02) in trial 10923 and 8.3 versus 6.7 months (log rank test, P=0.37) in trial 10961. Most patients with liver metastases alone have progression of their disease in their liver again (96 and 60% of patients in trials 10923 and 10961, respectively). Given the high prevalence of breast cancer, improved detection of liver metastases, encouraging survival achieved with currently available cytotoxic agents and the fact that a significant portion of patients with liver metastases alone have progression of their tumour in the liver again, a more aggressive multimodality treatment approach through prospective clinical trials seems worth exploring in this specific subset of women.

This article reviews the available data regarding the activity of second-line chemotherapy following 5-fluorouracil (5-FU), irinotecan (CPT-11) or oxaliplatin (OXA) alone or in combination. Studies undertaken in this setting, published both as full papers and in abstract form, were critically analyzed. The main conclusion is that clinical research for second and subsequent lines of treatment in advanced colon cancer (ACC) clearly needs to be optimized. A large number of small, non-randomized phase II trials have been reported without definitive conclusions. Efficient conduct of a limited number of high-quality randomized phase II trials with validation of promising regimens via phase III studies seems a preferable approach. This would not only accelerate the evaluation of new therapeutic options, but also, and more importantly, limit the number of patients receiving suboptimal treatments. The responsibility of this indispensable and urgent task lies with all researchers in this field and their partners in the pharmaceutical industry. One means to implement this approach is through strict selection of studies to be both presented and published, encouraging the spread of information provided by statistically well-designed and well-conducted trials that will eventually lead to the definition of the best standard of care for ACC patients. The conduct of repetitive phase II trials that test minor variations in dose and schedule, while commonplace, does little to advance the field.

Anthracyclines are among the most active cytotoxic drugs against breast cancer and are currently considered to be the standard agents for the adjuvant treatment of patients with node positive breast cancer. Nevertheless, the benefits attained by the use of the more active anthracycline schedules must be balanced against increased short- and long-term toxicity, and treatment options must be individualized for each patient. The authors review the available data regarding anthracycline efficacy and toxicity in the early breast cancer setting, the controversial issues still pending, and the potential directions for future research.