Common founder BRCA2 pathogenic variants and breast cancer characteristics in Ethiopian Jews.

PURPOSE: BRCA1/2 founder pathogenic variants (PVs) occur in various populations, but data on the mutational spectrum in Africans are limited. We examined BRCA1/2 PVs in breast cancer patients of Ethiopian Jewish (EJ) origin. METHODS: We retrospectively analyzed BRCA1/2 test results and clinical features of EJ breast cancer patients from seven medical institutions. We obtained heterozygote carrier rates in affected individuals from the laboratories of the largest Israeli HMO (Clalit). Population carrier frequency was determined in EJ controls. RESULTS: We identified three recurrent BRCA2 PVs in 11 EJ breast cancer patients (9 females, 2 males): c.7579delG, c.5159C > A, and c.9693delA. Only c.5159C > A was previously reported in Africans. In women, mean age at diagnosis was 35.7y; 8/9 were diagnosed with advanced disease. All tumors were invasive, 4/9 were triple negative. Only 3/11 carriers had relevant family history. Carrier rate in high-risk breast cancer patients was 11% (3/28; 95%CI [2.3%, 28.2%]). Combined carrier rate among controls was 1.8% (5/280; 95%CI [0.6%, 4.1%]). CONCLUSION: EJs harbor 3 recurrent BRCA2 PVs presenting with relatively severe breast cancer morbidity. Combined with the high BRCA2 carrier rate in the EJ population, these findings merit increasing awareness in this community and suggest that a culturally adapted population screening approach may be warranted.

Targeting pulmonary metastases of renal cell carcinoma by inhalation of interleukin-2.

INTRODUCTION: Pulmonary metastases of renal cell carcinoma (RCC) are associated with poor prognosis. Inhalation therapy with interleukin-2 (IL-2) is thus an appealing method for palliation. This multicenter study summarizes the national experience of IL-2 inhalation in patients with lung metastases of RCC. PATIENTS AND METHODS: Forty patients (median, 66.5 years of age) with radiologically documented progressing pulmonary metastases were enrolled. All patients had to be able to comply with inhalation technique, and were not candidates for other treatment options. Twenty-eight patients were systemic treatment-naïve. The protocol included three daily inhalations of IL-2 to a total dose of 18 MU. Treatment had to be continued until one of the following occurred: progression; a complete response; a life threatening toxicity; or patient refusal. Response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) system. RESULTS: The disease-control rate reached 57.5%, with a partial response rate of 2.5% and a disease stabilization rate of 55%. Median time to progression was 8.7 months. The main side-effects were cough and weakness. CONCLUSIONS: Inhalation of IL-2 for the treatment of pulmonary metastases in RCC is feasible, tolerable and beneficial in controlling progressive disease for considerable periods of time. The definition of response of biological therapy may need to be re-assessed and modified: stable disease should be regarded as a favorable response.

Vinorelbine-related acute cardiopulmonary toxicity.

Three cases of possible acute cardiopulmonary toxicity following the administration of vinorelbine are reported. The symptoms mimicked acute cardiac ischemia. However, neither ECG changes nor elevations of serum enzymes were observed. The outcome is favorable in 90% of patients developing this adverse event. The putative mechanism remains to be elucidated.

Prevalence of the I1307K APC gene variant in Israeli Jews of differing ethnic origin and risk for colorectal cancer.

BACKGROUND & AIMS: Israeli Jews of European birth, i.e., Ashkenazim, have the highest colorectal cancer incidence of any Israeli ethnic group. The I1307K APC gene variant was found in 6.1% of American Jews, 28% of their familial colorectal cancer cases, but not in non-Jews. We assessed the I1307K prevalence in Israeli Jews of differing ethnic origin and risk for colorectal cancer. METHODS: DNA samples from 500 unrelated Jews of European or non-European origin, with or without a personal and/or family history of neoplasia, were examined for the I1307K variant by the allele-specific oligonucleotide (ASO) method. RESULTS: In persons at average risk for colorectal cancer, I1307K was found in 5.0% of 120 European and 1.6% of 188 non-European Jews (P = 0.08). It occurred in 15.4% of 52 Ashkenazi Israelis with familial cancer (P = 0.02) and was not detected in 51 non-European Jews at increased cancer risk. Colorectal neoplasia occurred personally or in the families of 13 of 20 Ashkenazi I1307K carriers, 8 of whom also had a personal or family history of noncolonic neoplasia. CONCLUSIONS: The I1307K APC variant may represent a susceptibility gene for colorectal, or other, cancers in Ashkenazi Jews, and partially explains the higher incidence of colorectal cancer in European Israelis.

Computed tomography features of cerebral spread of malignant melanoma.

The CT features of cerebral involvement by metastatic malignant melanoma are described in 28 patients. The most common locations of the primary lesion were the trunk and lower limbs. There was a high incidence of extracerebral metastasis at the time of diagnosis of cerebral involvement. Headache and behavioral changes were the most frequent presenting symptoms; 7% of patients with asymptomatic. The cerebral metastases were classified by size (< 1 cm, 1-4 cm, > 4 cm), with more than half measuring 1-4 cm. The larger lesions usually occurred singly. Peritumoral edema was detected in 89% of patients, hemorrhage in 19%, pressure signs on the ventricles in 37%, midline deviation in 15%, and leptomeningeal spread in 11%. No correlation was noted between size of tumor and other radiological features. Unilateral involvement was documented in 44% of cases. In the majority of patients the metastases were located at the periphery of the brain, mostly in the temporal and parietal lobes. Neuroimaging studies of the brain in asymptomatic patients with malignant melanoma may reveal occult metastases and influence the choice of treatment.