A New de novo BRCA1 Mutation in a Young Breast Cancer Patient: A Case Report.

Background: BRCA1 and BRCA2 genes represent the most investigated breast and ovarian cancer predisposition genes. Ten cases of pathogenic de novo BRCA1 variations and six cases of pathogenic de novo BRCA2 variation have been reported at present. Here, we report a new case of a de novo BRCA1 gene mutation. Case Presentation: A 30-year-old woman with no health issues and no family history for hereditary breast and ovarian cancer was diagnosed with a hormone receptor positive/HER2 negative invasive breast cancer. Genetic testing revealed a pathogenic variant in BRCA1 (c.4065_4068delTCAA) which was not found in her parents or sister. Conclusion: We report a new case of de novo BRCA1 mutation, confirmed by repeated germline testing of the index patient and her parents. The published BRCA1/2 de novo mutation rate is low. This is probably due - in part - to the strict testing criteria.

Update Swiss guideline for counselling and testing for predisposition to breast, ovarian, pancreatic and prostate cancer.

This paper presents the Swiss guideline for genetic counselling and testing of individuals with an increased probability for carrying mutations in high risk cancer predisposition genes, particularly BRCA1 and BRCA2. It aims to help providers of genetic counselling to identify valuable candidates for testing and serves as a basis for reimbursement claims to Swiss insurance companies.

A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma.

OBJECTIVE: To evaluate the optimal sequence for the receptor tyrosine kinase inhibitors (rTKIs) sorafenib and sunitinib in metastatic renal cell cancer. METHODS: We performed a retrospective analysis of patients who had received sequential therapy with both rTKIs and integrated these results into a pooled analysis of available data from other publications. Differences in median progression-free survival (PFS) for first- (PFS1) and second-line treatment (PFS2), and for the combined PFS (PFS1 plus PFS2) were examined using weighted linear regression. RESULTS: In the pooled analysis encompassing 853 patients, the median combined PFS for first-line sunitinib and 2nd-line sorafenib (SuSo) was 12.1 months compared with 15.4 months for the reverse sequence (SoSu; 95% CI for difference 1.45-5.12, p = 0.0013). Regarding first-line treatment, no significant difference in PFS1 was noted regardless of which drug was initially used (0.62 months average increase on sorafenib, 95% CI for difference -1.01 to 2.26, p = 0.43). In second-line treatment, sunitinib showed a significantly longer PFS2 than sorafenib (average increase 2.66 months, 95% CI 1.02-4.3, p = 0.003). CONCLUSION: The SoSu sequence translates into a longer combined PFS compared to the SuSo sequence. Predominantly the superiority of sunitinib regarding PFS2 contributed to the longer combined PFS in sequential use.

A single dose of oral vitamin K effectively reverses oral anticoagulation with phenprocoumon during heart catheterisation.

QUESTION UNDER STUDY: To investigate the effectiveness of a single adjusted dose of oral vitamin K to temporarily reverse oral anticoagulation with phenprocoumon (Marcoumar) for heart catheterisation. METHODS: Patients under stable oral anticoagulation with phenprocoumon routinely scheduled for heart catheterizstion were given a single adjusted dose of oral vitamin K a day prior to the intervention. The customary anticoagulation scheme was kept unchanged with the exception of taking the double usual dose of phenprocoumon the evening after the intervention. The primary outcome was the achieved international normalised ratio (INR) immediately before the intervention. Secondary outcomes were the INR after one and four weeks, changes in phenprocoumon and coagulation factors II and VII and adverse events. RESULTS: 38 patients at a median age of 71 (63-74) years scheduled for heart catheterisation were included. The median INR changed from 2.2 (1.9-2.6) the day before to 1.5 (1.4-1.7) immediately before the intervention. An INR < or =1.5 respectively < or =1.8 was achieved in 61% and 95% of the patients. The INR values after one respectively four weeks were comparable to preintervention values. No thromboembolic or bleeding adverse events occurred during the study. CONCLUSION: A single adjusted oral dose of vitamin K given a day prior to heart catheterisation combined with a doubled phenprocoumon dose on the procedure day seems to be an easy applicable, safe and effective way to temporary reverse oral anticoagulation with phenprocoumon.

Spinal pain due to metastasis of unknown origin.

A 58-year-old woman presented with non-radicular pain in the upper thorax. Due to the prolonged duration of symptoms, a bone scintigraphy was made, which showed pathological enhancement in the upper thoracic spine. An MRI demonstrated lesions of the third and fourth thoracic vertebrae. A biopsy showed a metastasis of poorly differentiated carcinoma. A whole-body 18-F-FDG PET scan failed to identify a primary tumour. The patient was given radiotherapy, chemotherapy and analgesic treatment. She died within 3 years. In the late stage, the tumour marker CA 19-9 was positive; however, an MRI of the abdomen failed to identify a pancreatic tumour. Metastasis from an unknown primary site can present as cervical spinal disease very similar to degenerative disease.