BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients

To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not been characterized in the Turkish population. We investigated the presence of BRCA mutations in 53 individuals with a personal and family history of breast and/or ovarian cancer, and 52 individuals with a personal history of breast cancer diagnosed below age 50 without additional family history. We have identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques involving protein truncation test, direct sequencing and heteroduplex analysis. We found eight out of 53 patients (15.1%) with a family history to carry BRCA gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43 families presenting only breast cancer histories, and four were found in families presenting ovarian cancer with or without breast cancer. We also demonstrated two BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer cases without additional family history. Three of nine BRCA1 and both BRCA2 mutations detected in this study were not reported previously. These mutations may be specific to the Turkish population. The BRCA1 5382insC mutation, specific to Ashkenazi and Russian populations, was found twice in our study group, representing a possible founder mutation in the Turkish population. © 2000 Cancer Research Campaig

Efficacy and Tolerability of Lapatinib in the Management of Breast Cancer

Approximately 20%–25% of all breast cancers over express a key cell surface growth factor receptor known as HER2. HER2 plays a key role in cell growth and proliferation and is linked to worse clinical outcomes, making it a logical therapeutic target. The first HER2 targeted drug to be approved by the FDA, was the humanized monoclonal antibody trastuzumab, after it showed improvements in survival in the adjuvant setting, and delayed time to progression in the metastatic setting. Although highly effective, for reasons that are not clear, some patients display resistance to trastuzumab. Lapatinib is an oral, small molecule tyrosine kinase inhibitor, that inhibits both the HER1 ahd HER2 receptors and may be able to overcome trastuzumab resistance. Lapatinib is approved in the second line setting for use in combination with capecitabine or with letrozole. In this review, we will discuss the indications, concerns or any issues with regards to the drug

Glutathione <em>S</em>-transferase P1 (<em>GSTP1</em>) directly influences platinum drug chemosensitivity in ovarian tumour cell lines

BACKGROUND: Chemotherapy response in ovarian cancer patients is frequently compromised by drug resistance, possibly due to altered drug metabolism. Platinum drugs are metabolised by glutathione S-transferase P1 (GSTP1), which is abundantly, but variably expressed in ovarian tumours. We have created novel ovarian tumour cell line models to investigate the extent to which differential GSTP1 expression influences chemosensitivity. METHODS: Glutathione S-transferase P1 was stably deleted in A2780 and expression significantly reduced in cisplatin-resistant A2780DPP cells using Mission shRNA constructs, and MTT assays used to compare chemosensitivity to chemotherapy drugs used to treat ovarian cancer. Differentially expressed genes in GSTP1 knockdown cells were identified by Illumina HT-12 expression arrays and qRT–PCR analysis, and altered pathways predicted by MetaCore (GeneGo) analysis. Cell cycle changes were assessed by FACS analysis of PI-labelled cells and invasion and migration compared in quantitative Boyden chamber-based assays. RESULTS: Glutathione S-transferase P1 knockdown selectively influenced cisplatin and carboplatin chemosensitivity (2.3- and 4.83-fold change in IC(50), respectively). Cell cycle progression was unaffected, but cell invasion and migration was significantly reduced. We identified several novel GSTP1 target genes and candidate platinum chemotherapy response biomarkers. CONCLUSIONS: Glutathione S-transferase P1 has an important role in cisplatin and carboplatin metabolism in ovarian cancer cells. Inter-tumour differences in GSTP1 expression may therefore influence response to platinum-based chemotherapy in ovarian cancer patients

One-year prevalence and the impact of migraine and tension-type headache in Turkey: a nationwide home-based study in adults

Several studies have shown that the prevalence of migraine and tension-type headache (TTH) varied between different geographical regions. Therefore, there is a need of a nationwide prevalence study for headache in our country, located between Asia and Europe. This nationwide study was designed to estimate the 1-year prevalence of migraine and TTH and analyse the clinical features, the impact as well as the demographic and socio-economic characteristics of the participant households in Turkey. We planned to investigate 6,000 representative households in 21 cities of Turkey; and a total of 5,323 households (response rate of 89%) aged between 18 and 65 years were examined for headache by 33 trained physicians at home on the basis of the diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD-II). The electronically registered questionnaire was based on the headache features, the associated symptoms, demographic and socio-economic situation and history. Of 5,323 participants (48.8% women; mean age 35.9 ± 12 years) 44.6% reported recurrent headaches during the last 1 year and 871 were diagnosed with migraine at a prevalence rate of 16.4% (8.5% in men and 24.6% in women), whereas only 270 were diagnosed with TTH at a prevalence rate of 5.1% (5.7% in men and 4.5% in women). The 1-year prevalence of probable migraine was 12.4% and probable TTH was 9.5% additionally. The rate of migraine with aura among migraineurs was 21.5%. The prevalence of migraine was highest among 35–40-year-old women while there were no differences in age groups among men and in TTH overall. More than 2/3 of migraineurs had ever consulted a physician whereas only 1/3 of patients with TTH had ever consulted a physician. For women, the migraine prevalence was higher among the ones with a lower income, while among men, it did not show any change by income. Migraine prevalence was lower in those with a lower educational status compared to those with a high educational status. Chronic daily headache was present in 3.3% and the prevalence of medication overuse headache was 2.1% in our population. There was an important impact of migraine with a monthly frequency of 5.9 ± 6, and an attack duration of 35.1 ± 72 h, but only 4.9% were on prophylactic treatment. The one-year prevalence of migraine estimated as 16.4% was similar or even higher than world-wide reported migraine prevalence figures and identical to a previous nation-wide study conducted in 1998, whereas the TTH prevalence was much lower using the same methodology with the ICHD-II criteria

Totally implantable venous-access ports: local problems and extravasation injury

Totally implantable venous-access ports (TIVAPs) are valuable instruments for long-term intravenous treatment of patients with cancer, but implantation and use of these devices are each associated with complications. In addition to the perioperative problems, long-term complications can arise; these can be classified in five categories -catheter malfunction, catheter-related venous thrombosis, catheter-related infection, port-related complications, and extravasation injury. Such complications reduce the benefits of reliable access to the venous system in patients with malignant tumours. The vast majority of such disadvantages are attributable to inexpert handling of ports and, therefore, should be avoidable. TIVAP placement procedures and TIVAP complications are discussed in this review, with special emphasis on local problems and extravasation injuries. To obtain maximum benefit from TIVAPs, all health-care personnel must be familiar with the use and routine maintenance procedures of the devices and treatment options for catheter-related complications

Safety of paclitaxel in a patient with ovarian cancer and hyperbilirubinemia due to Rotor's syndrome.

Background. Rotor's syndrome is a rare congenital disorder characterized by functional hyperbilirubinemia. Treatment decision may be challenging in a cancer patient with Rotor's syndrome, since the majority of the antineoplastic agents are metabolized in the liver and excreted via the biliary system. We report the first case of paclitaxel administration in a patient with ovarian cancer and elevated bilirubin levels due to Rotor's syndrome

Stevens-Johnson syndrome in a patient receiving anticonvulsant therapy during cranial irradiation.

A 28-year-old female patient with a recent history of breast carcinoma was referred to our clinic with generalized necrotic skin eruptions and severe mucosal erosions, which developed right after the completion of cranial radiotherapy for brain metastases. She had been receiving prophylactic diphenylhydantoin treatment 100 mg three times daily during radiation therapy. The extensive involvement of the oral mucosa with conjunctivitis and synechiae of the eyelids, facial swelling, and extension of the rash over the trunk and shoulders with bullous detachment of less than 10% of the total body surface strongly suggested Stevens-Johnson syndrome caused by phenytoin treatment in our patient. There has been conflicting evidence on the role of radiotherapy in the increased risk of severe drug reactions. Although various authors have emphasized the augmented rate of severe mucocutaneous reactions caused by anticonvulsants given during radiotherapy and suggested discontinuing the prophylactic use of such drugs in patients with no history of seizures, others have argued in favor of prophylactic anticonvulsants. Given the high risk of seizures, reaching 20% in patients with brain tumors, and the low incidence of drug reactions, the suggestion of refraining from prophylactic anticonvulsants in the setting of primary or metastatic brain tumors is controversial

Oral etoposide (VP16) in platinum-resistant epithelial ovarian cancer (EOC)

This phase II study evaluates the efficacy and toxicity of a prolonged schedule second-line and third-line treatment of oral VP16 in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Twenty-two eligible women with progressive or relapsed ovarian cancer resistant to platinum-based therapy were included in this study. All the patients had received more than one prior treatment, and had evidence of disease progression within 6 months of the previous chemotherapy. Eleven patients had received more than two different chemotherapy regimens. Fifteen patients had received consolidation therapy with intraperitoneal cisplatin after an initial treatment course with six cycles of a platinum-based combination regimen. All patients with measurable disease observed in abdominal computed tomography scans were given oral VP16 at a daily dose of 50 mg/m(2) for 14 consecutive days with 4 weekly intervals. Among 22 assessable patients, there were one complete response (CR) and three partial responses (PR), so the objective response rate, which is the addition of CR and PR rates, was 18%. Seven patients (32%) had stable disease. Median duration of response and stable disease was 2.5 months (range: 1-10 months). Overall median survival was 11 months from study entry (range: 3-36 months). Toxicity for most patients was mild, but a few severe myelotoxicities occurred, and there were no treatment-related deaths. According to World Health Organization toxicity criteria grade III/IV thrombocytopenia was seen in 4 of 22 patients, grade III/IV neutropenia in 6 of 22 patients, and grade III anemia was observed in 3 of 22 patients. Non-hematologic toxicity was mild, and mucositis was the most frequently observed nonhematologic toxicity. Oral etoposide has considerable activity with a tolerable toxicity profile for the treatment of platinum-resistant epithelial ovarian cancer