Induction of Endothelial Cell Apoptosis by Solid Tumor Cells

The mechanisms by which tumor cells extravasate to form metastasis remain controversial. Previous studies performed in vivo and in vitro demonstrate that the contact between tumor cells and the vascular wall impairs endothelium integrity. Here, we investigated the effect of breast adenocarcinoma MCF-7 cells on the apoptosis of human umbilical vein endothelial cells (HUVEC). TUNEL labeling, nuclear morphology, and DNA electrophoresis indicated that MCF-7 cells induced a two- to fourfold increase in HUVEC apoptosis. Caspase-3 activity was significantly enhanced. Neither normal cells tested (mammary epithelial cells, fibroblasts, leukocytes) nor transformed hematopoietic cells tested (HL60, Jurkat) induced HUVEC apoptosis. On the contrary, cells derived from solid tumors (breast adenocarcinoma, MDA-MB-231 and T47D; fibrosarcoma, HT 1080) had an effect similar to that of MCF-7 cells. The induction of apoptosis requires cell-to-cell contact, since it could not be reproduced by media conditioned by MCF-7 cells cultured alone or cocultured with HUVEC. Our results suggest that cells derived from solid tumors may alter the endothelium integrity by inducing endothelial cell apoptosis. On the contrary, normal or malignant leukocytes appear to extravasate by distinct mechanisms and do not damage the endothelium. Our data may lead to a better understanding of the steps involved in tumor cell extravasation

Management of estrogen deficiency after breast cancer

peer reviewedThe prevention and the treatment of oestrogen deficiency induced by breast cancer treatments are crucial in the management of patients. The impacts of this deficiency must not be neglected: quality of life impairments inducing eventually premature withdrawal of hormonotherapies, and excess of bone and cardio-vascular morbidities and mortalities, especially in good prognosis young women. Management strategies of short and long term effects of this deficiency are reviewed and discussed here

Breast cancer in Belgium: why are we the first in Europe?

peer reviewedBreast cancer incidence in Belgium is on the top of European countries, with 9.697 new cases in 2008 and 106/100.000 women/year. The explanation of this high incidence in our country is probably the accumulation of risk factors (many of them are linked to lifestyle), and the impact of screening and registration of cases. The relative impact of each of theses factors is less clear because we don't have powerful statistical studies. Belgium is slightly above the European mean for breast cancer mortality, with 19,4/100.000 women/year and an all stages 15-year survival of 75%. Breast cancers are responsible for around 3% of all-cause mortality in Belgian women. This article discusses the causes of this high Belgian incidence and of current decrease of incidence in western countries, and reviews known and less known risk factors of breast cancers, with a special focus on menopause hormonal treatments

Hormone Replacement Therapy after Breast Cancer. Yes...Or No?

peer reviewedClinical and experimental studies indicate that combined unique conjugated estrogens and medroxyprogesterone acetate moderately increase the risk of breast cancer in postmenopausal women. Classically, hormone replacement therapy is contra-indicated in women with a past history of breast cancer due to the fear of recurrence. However, these postmenopausal patients complain about hot flushes and adjuvant hormonal therapies (such as aromatase inhibitors, SERMs and Tamoxifen...) aggravate their symptoms. Observational studies and their meta-analyses do not show a deleterious effect but rather a beneficial impact of hormone replacement therapy among women with a past history of breast cancer. We summarise all these studies and their biological, clinical and epidemiological interpretations. We conclude that short term hormone replacement therapy is safe among those women requesting a replacement therapy after complete information. It is however advisable to conclude definitely only when prospective randomised trials with estradiol or tibolone (a promising alternative) will be available. Such ongoing studies will allow to conclude definitely the possible benefits and risks of hormone replacement therapy among patients with a past history of breast cancer

Revised Postmenopausal Treatments? A New Polemic!

peer reviewedThe study by Schairer et al. aims to determine whether increases in risk of breast cancer associated with the estrogen-progestin regimen are greater than those associated with estrogen alone. This study is a cohort of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program that involved 29 screening centers throughout the United States. A total of 46,355 postmenopausal women were followed. During follow up, 2,082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years. The relative risk increased by 0.01 with each year of estrogen-only use and by 0.08 with each year of estrogen-progestin-only use among recent users. Among women with a Body Mass Index of 24.4 kg/m2 or less, increases in relative risk with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 and 0.12, respectively. The authors conclude that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone. This study was largely commented in the lay media. Unfortunately the Belgian media introduced the confusion between the relative risk and the risk attributable to estrogen and estrogen-progestin. The aim of this manuscript is to precisely inform our colleagues, to analyze the Schairer study and to present the actual figures of risk associated with the use of estrogen and estrogen-progestin replacement therapy. Finally, we formulate some suggestions for the physician to whom the patient declares: "Did you read the negative effects of hormones?". What should we advice

Hormone Therapy and Breast Cancer Risk

Hormone therapy (HT) is the most efficacious intervention for the relief of climacteric symptoms. Controversies surrounding HT have left many women puzzled and afraid. Gynecologists are faced with long-standing beneficial assumptions challenged by an abundance of robust detrimental new data, with little guidance on how to interpret these findings. Prescriptions for HT (and incidence of breast cancers in some areas) have fallen over the last 3 years due to anxiety provoked about breast cancer risk and recurrence. The current 'clinical climate' is against HT. Due to a lack of effective alternatives, women suffering from estrogen-deficiency symptoms are still requesting objective information about HT, particularly those at higher risk of breast cancer or those with a past history of breast cancer. In this situation, discussion of the current clinical uncertainty surrounding the use of HT must be undertaken to ensure that women are adequately informed. The objective of this presentation is to provide a framework for understanding breast cancer risk associated with HT. What are the precise molecular mechanisms of estrogen and progestin in the initiation of breast cancer? Does the risk of estrogen-only therapy on breast cancer vary by dose, constituent, route and duration of administration and cessation of use? Does HT, in addition to increasing risk for breast cancer, affect the type of breast cancer (lobular and ductal) diagnosed? Is HT associated with breast cancers that have better prognostic factors? How relevant are the changes in mammographic breast density associated with HT for the evaluation of breast cancer risk? What is the additional global health risk/benefit ratio associated with the selective use of progesterone or progestin that may confer a significant cardiovascular benefit, such as drospirenone? It is currently assumed and tested that new hormones with particular pharmacological profiles may ultimately achieve their therapeutic goal of relieving climacteric symptoms without an associated moderate increased risk of breast cancer

Transdermal Replacement Hormone Therapy: A Trend or an Advantage?

peer reviewedThis review describes the clinical usefulness of transdermal hormone replacement therapy. This route of administration is particularly important in women with hypertriglyceridemia, in hypertensive postmenopausal women, in women who smoke or have an increased risk of biliary or liver disorder, for those who display a reduced glucose tolerance or in women who are at risk of thrombotic disorders. The avoidance of the "first passage effect" is ensured by the transdermal application of estrogen and probably explains the superiority of this route of steroid administration

Adherence to long-term medication : the particular case of the adjvant endocrine therapy for breast cancer

peer reviewedL'objectif de l'hormonothérapie adjuvante dans le cancer du sein est d'atteindre en pratique quotidiennee, une efficacité comparable à celle obtenue au cours des études cliniques. Malgré l'efficacité démontrée de l'hormonothérapie, la compliance constitue un défi majeur et un problème multidimensionnel. Une meilleure compréhension des raisons de cette non-compliance aiderait à mieux identifier les patientes à risque et à développer des interventions capables d'améliorer l'adhésion à l'hormonothérapie adjuvante.C'est dans ce but que nous avons entrepris une revue de la littérature des six dernières années (Pub Med 2003-2006)