Primary care physicians' knowledge and attitudes towards genetic testing for breast-ovarian cancer predisposition

Background: Primary health care providers are expected to be directly involved in the genetic testing for cancer susceptibility. This study assessed physicians' knowledge, attitude and perception of their role towards testing for hereditary breast-ovarian cancer. Design: A mail-in survey was sent to all general practitioners, internists, obstetrician-gynecologists and oncologists in private practice in Geneva county, Switzerland. Questions included socio-demographic variables, knowledge about hereditary breast-ovarian cancer, attitude towards testing and assessment of their role in the pre- and post-test procedure. Results: Two hundred fifty-nine (65%) of four hundred questionnaires were returned of which two hundred forty-three (61%) were analysed. Response rates were similar between specialties; women answered more frequently. The majority of the respondents (87%) approved of genetic susceptibility testing. The most common objection to testing was the absence of approved strategies for the prevention and detection of early breast cancer. Most physicians felt they had an active part to play in the pre-test procedure, the disclosure of results, and especially the consultants' long-term care and support (99%). Physicians correctly answered a third (32%) of the knowledge questions. The abstention rate for individual items ranged from 13% to 60%. Scores varied by specialty. Oncologists were more knowledgeable than gynecologists, internists and general practitioners. Conclusions: The majority of the primary care physicians in this study have a favourable attitude and are ready to play a prominent role in genetic counseling and testing for breast-ovarian cancer predisposition. Defective knowledge scores, however, underline the need for targeted educational program

Malignant glioma: Should chemotherapy be overthrown by experimental treatments?

Despite more than two decades of clinical research with chemotherapy, the outcome of malignant gliomas remains poor. Recent years have seen major advances in elucidation of the biology of these tumors, which in turn have led to the current development of innovative therapeutic strategies. The question confronting us at the end of the 1990s is whether we should continue to use and investigate chemotherapy or whether the time has come for experimental treatments. As a contribution to this debate, we reviewed the abundant literature on chemotherapy of malignant glioma, paying special attention to methodological features. The new treatment approaches based on current knowledge about glioma biology are then briefly summarized. Assessment of more than 20 years of chemotherapy trials is discouraging despite a few areas of modest success. Only patients with specific histology (oligodendroglioma, anaplastic astrocytoma) and good prognostic factors (young age, good performance status) may benefit from chemotherapy, with a possible reversal of neurological dysfunction. However, the real impact on survival is small (anaplastic astrocytoma) or undefined (oligodendroglioma). Furthermore, it is unfortunately obvious that the outcome of glioblastoma patients is not significantly modified by chemotherapy. We believe the time has come to explore the potential of novel biological therapies in glioblastoma patients. This could also be proposed for anaplastic astrocytoma and oligodendroglioma patients after failure of chemotherap

Infusional ECarboF in patients with advanced breast cancer: A very active and well-tolerated out-patient regimen

We performed a trial using the combination of epirubicin 50 mg/m2/day 1, carboplatinum AUC 5/day 1 and continuous 5-fluorouracil (5-FU) 200 mg/m2/day (every 4 weeks for 6 months) to confirm the efficacy and low toxicity profile of this regimen in breast cancer. In 51 patients with metastatic (n = 33) or locally advanced (n=18) breast cancer the overall response rate was 86% (95% confidence interval (95% CI): 73%-94%): 94% in locally advanced and 81% metastatic disease. Grade 3-4 toxicity was low: 4% of patients presented with febrile neutropenia, 16% with severe palmar-plantar syndrome, 10% with Port-a-cath thrombosis. This study confirms the high efficacy of infusional 5-FU-based regimens and justifies further research into novel promising oral 5-FU derivative

Set-up of a population-based familial breast cancer registry in Geneva, Switzerland: validation of first results

Background: This article evaluates the accuracy of family history of breast and ovarian cancer among first-degree relatives of breast cancer patients, retrospectively collected during the setting up of a population-based family breast cancer registry. Patients and methods: Family histories of cancer for all women with breast cancer recorded at the Geneva Cancer Registry from 1990 to 1999 were retrospectively extracted from medical files. The accuracy of these family histories was validated among Swiss women born in Geneva: all 119 with a family history of breast (n = 110) or ovarian (n = 9) cancer and a representative sample of 100 women with no family history of breast or ovarian cancer. We identified the first-degree relatives of these women with information from the Cantonal Population Office. All first-degree relatives, resident in Geneva from 1970 to 1999, were linked to the cancer registry database for breast and ovarian cancer occurrence. Sensitivity, specificity and level of overall agreement (κ) were calculated. Results: Among 310 first-degree relatives identified, 61 had breast cancer and six had ovarian cancer recorded at the Geneva Cancer Registry. The sensitivity, specificity and κ of the reported family histories of breast cancer were 98%, 97% and 0.97, respectively. For ovarian cancer, the sensitivity, specificity and κ were 67%, 99%, and 0.66, respectively. Conclusions: This study indicates that retrospectively obtained family histories are very accurate for breast cancer. For ovarian cancer, family histories are less precise and may need additional verificatio

Absence of Host Plasminogen Activator Inhibitor 1 Prevents Cancer Invasion and Vascularization

Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. High levels of components of the plasminogen activation system, including urokinase, but paradoxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1), have been correlated with a poor prognosis for some cancers. We report here that deficient PAI1 expression in host mice prevented local invasion and tumor vascularization of transplanted malignant keratinocytes. When this PAI1 deficiency was circumvented by intravenous injection of a replication-defective adenoviral vector expressing human PAI1, invasion and associated angiogenesis were restored. This experimental evidence demonstrates that host-produced PAI is essential for cancer cell invasion and angiogenesis