Non-Publication Is Common among Phase 1, Single-Center, Not Prospectively Registered, or Early Terminated Clinical Drug Trials.

The objective of this study was to investigate the occurrence and determinants of non-publication of clinical drug trials in the Netherlands.All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followed-up from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination.

Occurrence and determinants of selective reporting of clinical drug trials: design of an inception cohort study.

Introduction: Responsible conduct of research implies that results of clinical trials should be completely and adequately reported. This article describes the design of a cohort study that aims to investigate the occurrence and the determinants of selective reporting in an inception cohort of all clinical drug trials that were reviewed by the Dutch Institutional Review Boards (IRBs) in 2007. It also describes the characteristics of the study cohort.

[Patient safety in clinical intervention research].

In clinical intervention research, the monitoring of patient safety is essential. In December 2009, a symposium on the role of the different parties involved was organised. Research starts with a robust protocol with a section dealing with interim decision-making and procedures for reporting during the research.

Sensitivity to first-line chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers.

Purpose: Preclinical as well as a few small retrospective, neoadjuvant studies suggest that breast cancer (cells) without functional BRCA1 or BRCA2 protein have an increased sensitivity to some chemotherapeutic agents causing double-strand DNA breaks. In this study we assessed the sensitivity to standard first-line chemotherapy of metastatic BRCA1/2-associated breast cancer, compared with sporadic breast cancer patients.

Patients And Methods: From the Family Cancer Clinic database, we selected 93 BRCA1- and 28 BRCA2-associated breast cancer patients treated with chemotherapy for metastatic disease before January 1, 2007.

Standard psychological consultations and follow up for women at increased risk of hereditary breast cancer considering prophylactic mastectomy.

Background: Women at increased (genetic) risk of breast cancer have to weigh the personal pros and cons of prophylactic mastectomy (PM) as an option to reduce their cancer risk. So far, no routine referral to a psychologist has been investigated for women considering PM. Aim of this study was to asses: 1) the acceptance of the offer of a standard psychological consultation as part of pre-surgical decision-making in high-risk women, 2) reasons for PM and reasons for postponing it, 3) the need for additional psychological interventions, and factors associated, and 4) the frequency of psychiatric/psychological treatment history.

A family history of breast cancer will not predict female early onset breast cancer in a population-based setting.

Background: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data from cancer-prone families or from BRCA1/2 mutation families, and might be biased because BRCA1/2 mutations explain only a small proportion of the familial clustering of breast cancer. The aim of the current study was to determine the predictive value of a family history of cancer with regard to early onset of female breast cancer in a population based setting.

Distant disease-free interval, site of first relapse and post-relapse survival in BRCA1- and BRCA2-associated compared to sporadic breast cancer patients.

Background: Data on distant disease-free interval (DDFI) and the localization of the first distant metastasis (DM) in BRCA1- and BRCA2-associated breast cancer (BC) patients are as yet scarcely available.

Patients And Methods: We identified 57 BRCA1-associated and 31 BRCA2-associated BC patients, diagnosed between 1980 and 2001, and developing DM disease before 2004, July 1. DDFI, the site(s) of first DM and post-relapse survival of these patients were compared with those of 192 sporadic BC patients.

Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of hereditary breast cancer: long-term experiences at the Rotterdam Family Cancer Clinic.

Background: BRCA1/2 mutation carriers and women from a hereditary breast(/ovarian) cancer family have a highly increased risk of developing breast cancer (BC). Prophylactic mastectomy (PM) results in the greatest BC risk reduction. Long-term data on the efficacy and sequels of PM are scarce.

Factors affecting sensitivity and specificity of screening mammography and MRI in women with an inherited risk for breast cancer.

Background: The MRISC study is a screening study, in which women with an increased risk of hereditary breast cancer are screened by a yearly mammography and MRI, and half-yearly clinical breast examination. The sensitivity found in this study was 40% for mammography and 71% for MRI and the specificity was 95 and 90%, respectively. In the current subsequent study we investigated whether these results are influenced by age, a BRCA1/2 mutation, menopausal status and breast density.

Satisfaction with prophylactic mastectomy and breast reconstruction in genetically predisposed women.

Background: Prophylactic mastectomy with breast reconstruction is a risk-reducing strategy for women at increased risk of breast cancer. It remains a very radical intervention, and long-term data on satisfaction are insufficiently available. In the present follow-up study, the authors assess satisfaction with prophylactic mastectomy and breast reconstruction and its impact on sexual relationships.

Differences between first and subsequent rounds of the MRISC breast cancer screening program for women with a familial or genetic predisposition.

Background: Within the Dutch MRI Screening (MRISC) study, a Dutch multicenter screening study for hereditary breast cancer, the authors investigated whether previously reported increased diagnostic accuracy of magnetic resonance imaging (MRI) compared with mammography would be maintained during subsequent screening rounds.

Methods: From November 1999 to October 2003, 1909 eligible women were included in the study. Screening parameters and tumor characteristics of different rounds were calculated and compared.

Selection bias influences reported contralateral breast cancer incidence and survival in high risk non-BRCA1/2 patients.

Purpose: The results of studies comparing survival in familial and sporadic breast cancer (BC) are inconsistent. A higher incidence of contralateral breast cancer (CBC) has been reported in familial BC. Ascertainment bias may influence both the reported familial CBC and survival.

Hereditary breast cancer growth rates and its impact on screening policy.

Imaging is often performed yearly for the surveillance of BRCA1/2 mutation carriers and women at high familial breast cancer risk. Growth of cancers in carriers may be faster as these tumours are predominantly high grade. Quantitative data on tumour growth rates in these 2 groups are lacking.

Outcome of surveillance and prophylactic salpingo-oophorectomy in asymptomatic women at high risk for ovarian cancer.

Objective: Women at high risk of ovarian cancer are currently offered two options: either surveillance or prophylactic bilateral salpingo-oophorectomy. The efficacy and outcome of surveillance remain unclear.

Methods: We performed a retrospective study.

Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition.

Background: The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women.

Methods: Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings.

Use of genetic testing and prophylactic mastectomy and oophorectomy in women with breast or ovarian cancer from families with a BRCA1 or BRCA2 mutation.

Purpose: To analyze the use of genetic testing, prophylactic mastectomy, and oophorectomy among women with breast and/or ovarian cancer from families with a BRCA1 or BRCA2 mutation.

Patients And Methods: We examined prospectively the use of BRCA1/BRCA2 testing in all women with a primary breast or ovarian cancer from a consecutive series of 112 high-risk families in which a BRCA1/BRCA2 mutation eventually was identified. The rate of prophylactic bilateral and contralateral mastectomy and prophylactic oophorectomy was analyzed in the women who carried a BRCA1/BRCA2 mutation and who had no metastatic disease at the time of the genetic test disclosure.

Risk factors and risk reduction of breast and ovarian cancer.

Purpose Of Review: Breast and ovarian cancer remain a significant burden for women living in the Western world. This paper reviews the risk factors and current strategies to prevent these diseases.

Recent Findings: Established factors associated with the risk of breast cancer include family history, reproductive factors and lactation, as well as age at menarche and menopause.

One year follow-up of women opting for presymptomatic testing for BRCA1 and BRCA2: emotional impact of the test outcome and decisions on risk management (surveillance or prophylactic surgery).

Genetic testing enables women at risk for hereditary breast and/or ovarian cancer to find out whether they have inherited the gene mutation (BRCA1/BRCA2), and if so, to opt for frequent surveillance and/or prophylactic surgery (bilateral mastectomy and/or oophorectomy). Here, a follow-up is described for 63 healthy women at 50% risk of being a BRCA1/BRCA2 mutation carrier who underwent genetic testing. The course of distress and problems regarding body image and sexuality up to 1 year after disclosure of the test-outcome were described separately for mutation carriers undergoing mastectomy (n = 14), for mutation carriers opting for surveillance (n = 12) and for non-mutation carriers (n = 37).