Search

Background In view of the increased risk of developing breast (BC) cancer, BRCA mutation carriers are offered intensive surveillance or risk reducing mastectomy (RRM) and/or salpingo-ovariectomy (RRSO). It is insufficiently clear how to counsel mutation carriers who have been treated for OC, and it may be questioned whether RRM is indicated. It is possible that BC risk, both of primary (PBC) and contralateral BC (CBC), may be modified by the treatment given for OC mostly including surgery and platinum-based chemotherapy. Further, the BC risk has to be weighted against the risk of death after OC. So far, there are no data available on the PBC or CBC risk after OC in BRCA mutation carriers. Patients and Methods From the database of the institutional Family Cancer Clinic (FCC), we selected BRCA-associated OC patients either without (n= 79, at risk of PBC) or with a history of unilateral BC (n=37, at risk of CBC). Controls were BRCA mutation carriers without OC, either without (n=351) or with a history of unilateral BC (n=294). Follow-up started at OC diagnosis, and for controls at date of first visit at the FCC or the 35th birthday. Exclusion criteria were: other malignancy besides epithelial OC or BC, inadequate follow-up data, bilateral breast cancer or mastectomy. Data analyses were performed using t- and chi-squared tests, and Kaplan-Meier survival method with death prior to BC as competing risk event. Results Only six OC patients (5.1%) did not receive chemotherapy as part of primary therapy for OC, five at risk of PBC and one at risk of CBC. Chemotherapy schedules were mainly platinum-based (92%). RRSO was performed in 45% of the controls. The risks of PBC at 2, 5, and 10 years in BRCA-associated OC patients were 3%, 6% and 11%, respectively, versus 6%, 16% and 28% in unaffected BRCA mutation carriers (p=0.03). The mortality rate at those time points in the OC group was 13%, 33% and 61%, respectively, versus 1%, 2% and 2% in unaffected mutation carriers (p In patients with a history of unilateral BC, the risks of CBC at 2, 5, and 10 years in OC patients were 0%, 7% and 7%, respectively, versus 6%, 16% and 34% in the BC patients without OC (p=0.06). The mortality rate at similar time points was 19%, 34%, and 55%, respectively, in the OC group versus 4%, 11%, and 21% for the non-OC patients (p Conclusions The risk of developing a PBC or CBC was much lower in BRCA mutation carriers with a history of OC than in mutation carriers without OC. Also, since the 10-year mortality rate after ovarian cancer was 55–60% and the risk of developing a PBC or CBC at the highest was 11% over the same time period, our data suggest that intensive breast cancer surveillance strategies for the BRCA-associated ovarian cancer group might be reconsidered, while risk reducing mastectomy is not indicated unless in specific cases requiring careful consideration in a multisciplinary setting. Further studies in larger groups are warranted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-04.

The increasing cost of drug development has raised the demand on the use of biomarkers as surrogate endpoints for the evaluation of new drugs in clinical trials. However, failed past attempts to use surrogate endpoints made it clear that, before deciding on the use of a candidate surrogate endpoint, it is of the utmost importance to investigate its validity. Such validation process has proven challenging for conceptual and practical reasons. In the present chapter, some of the statistical methods introduced for the evaluation of surrogate markers will be discussed. Emphasis will be made on the so-called meta-analytic approach and its information-theoretic version, where information from several units is combined to carry out the validation exercise. The methods will be illustrated using a case study in ophthalmology.

In this paper we examine the perceptions of entrepreneurs and other concerned individuals: which factors do they consider critical for success in the innovation process? From the perspective of the respondents, the entrepreneur is the most important factor in the innovation process. Internal aspects dominate not only the list of success factors but also the top of the list. Extemal aspects appear only in the third and even the fourth clusters. A few aspects are believed to be more important for the manufacturing sector than for the service sector. These are unique product advantages, marketing activities, pre-development, competition and collaboration. The subgroups of responding entrepreneurs and non-entrepreneurs revealed hardly any differences. Nor were there many significant scale differences. Statistically, we may conclude that the entrepreneurs do not consider external circumstances very important aspects of innovation success. They have a rather egocentric point of view, in that they place themselves and the internal process on top (which they are in a position to influence). External aspects follow much later. This attitude obviously entails a considerable risk of over-estimation.

The informative value given by the announcement of distribution of dividend has already been investigated. One of the leading studies on this matter is Lintner (1956). Lintner found a relation between mutation in dividend, profits in the current financial year and the dividend in the last financial year. This dividend-model is known as the Lintner-model. When the mutation in the dividend differs from what was to be expected by this dividend-model, Lintner finds this to have informative value regarding the amount of profit in the future. In 197 1 I/B/E/S International started a financial data-file, The Institutional Brokers Estimate System (I/B/E/S). This data-file contains the expectations of the analysts regarding profit. Since 1989 I/B/E/S is collecting this data also for Dutch firms. In this article an extra variable is added to the Lintner-model, namely the expectations collected by I/B/E/S mentioned above. The purpose of this article is to find out if there is still informative value regarding the amount of profit in the future when the mutation in the dividend differs from what was to be expected by this adjusted Lintner-model.