Early occurrence of lung adenocarcinoma and breast cancer after radiotherapy of a chest wall sarcoma in a patient with a de novo germline mutation in TP53.

We report a 26-year-old female patient who was diagnosed within 4 years with chest sarcoma, lung adenocarcinoma, and breast cancer. While her family history was unremarkable, DNA sequencing of TP53 revealed a germline de novo non-sense mutation in exon 6 p.Arg213X. One year later, she further developed a contralateral ductal carcinoma in situ, and 18 months later a jaw osteosarcoma. This case illustrates the therapeutic pitfalls in the care of a young cancer patient with TP53 de novo germline mutations and the complications related to her first-line therapy. Suggestion is made to use the less stringent Chompret criteria for germline TP53 mutation screening. Our observation underlines the possibly negative effect of radiotherapy in generating second tumors in patients with a TP53 mutation. We also present a review of six previously reported cases, comparing their cancer phenotypes with those generally produced by TP53 mutations

A similar 24-h blood pressure control is obtained by zofenopril and candesartan in primary hypertensive patients

Objective. To compare the antihypertensive effect of treatment with zofenopril vs candesartan by office and ambulatory blood pressure (BP). Design and methods. Following a 2-week wash-out from previous treatment, 236 grade I-II primary hypertensive patients were randomized double-blind to 12 weeks treatment with zofenopril 30 mg or candesartan 8 mg od. After 4 weeks, treatment was doubled in responder non-normalized (office systolic BP≥140 mmHg and office diastolic BP reduction ≥10 mmHg) or non-responder patients (office systolic BP≥140 mmHg and office diastolic BP reduction <10 mmHg). Following a further 4 weeks, non-responder non-normalized patients were withdrawn. Results. In the intention-to-treat population, office systolic BP and diastolic BP reductions after 12 weeks of treatment were similar between the two groups (zofenopril: 21±11/15±8 mmHg, n=114 vs C: 20±11/15±7 mmHg (candesartan; p=NS). Also 24-h ambulatory BPs were equally reduced by zofenopril and candesartan (7±13/ 5±8 mmHg vs 7±12/5±8 mmHg; p=NS). The trough-to-peak ratio and smoothness index were not sigficantly different between zofenopril and candesartan. Tolerability of both drugs was good. Conclusions. Monotherapy with zofenopril and candesartan similary reduced office and 24-h BPs. Since almost 90% of patiens were normalized by either zofenopril or candesartan, this result suppots the importance of considering low- or high-dose monotherapies as initial for most hypertensive patients of mild degree