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Kerstin Rhiem

Publications and source records attributed to Kerstin Rhiem.

7 recordsLinked to original sources
PubMed2006

Screening for ovarian cancer by transvaginal ultrasound and serum CA125 measurement in women with a familial predisposition: a prospective cohort study.

OBJECTIVE: This study evaluates the accuracy of transvaginal ultrasound (TVUS) in combination with CA125 to detect ovarian cancer in women at hereditary risk for ovarian cancer. METHODS: A semi-annual surveillance protocol comprising CA125 measurement and TVUS was offered to 676 women including 85 BRCA mutation carriers. Surgical intervention was performed if TVUS revealed a suspicious cyst or if elevated CA125 levels or cystic lesions persisted in two consecutive examinations. RESULTS: Ten women underwent histological verification that revealed one serous cystadenocarcinoma stage Ic. No interval ovarian cancer occurred. The specificity of surgical intervention reached 98.7% (95% confidence interval (CI): 97.5% to 99.3%) and a positive predictive value (PPV) of 10% (95% CI: 1.8% to 40.4%). CONCLUSION: The low PPV is due to the unexpectedly low incidence of ovarian cancer. Large scale investigations including details on potential confounders and modifiers are needed to further evaluate accuracy and effectiveness of ovarian cancer screening for women at high risk.

Adult↗
PubMed2006

Outcome of a structured surveillance programme in women with a familial predisposition for breast cancer.

We aimed to prospectively evaluate the efficacy of a multi-modal surveillance programme for the early detection of familial breast cancer. Ultrasound, mammography and breast magnetic resonance imaging were evaluated in 413 women who participated in a prospective study with a median follow-up of 2.2 years (range 1-6.75 years). Of these, 49 women carried a BRCA mutation, 203 were at high and 161 at moderate risk. Breast carcinomas diagnosed within the programme were compared with 297 carcinomas previously observed in the risk group and 7894 carcinomas documented in the regional cancer registry within the same time period. Overall, 41 breast carcinomas and no interval carcinoma were detected. The detection rates averaged 107.2/1000 for mutation carriers with highest rates between 20 and 39 years of age, 45.8/1000 for high-risk women with highest rates between 40 and 49 years of age and 23.9/1000 for moderate-risk women with highest rates between 50 and 74 years of age. Overall, 82.8% of the breast carcinomas were node negative and 85.4% pre-invasive or smaller than 2 cm. In comparison, of breast carcinomas detected outside the programme only 47.8% were node negative (P=0.0005) and 43.8% pre-invasive or smaller than 2 cm (P<0.000 01). Of those gathered in the local cancer registry 55.7% were node negative (P=0.004) and 47.6% pre-invasive or smaller than 2 cm (P<0.000 01). Our data indicate that (1) there is a strong correlation between breast cancer detection rates, risk status and age at disease onset and (2) a multi-modal surveillance programme can detect early-stage hereditary breast carcinomas.

Adult↗
PubMed2005

Systematic identification and molecular characterization of genes differentially expressed in breast and ovarian cancer.

The identification of novel disease-associated genes in gynaecological tumours has important implications for understanding the process of tumourigenesis and the development of novel treatment regimens. cDNA libraries from disease tissues may represent a valuable source to identify such genes. Recently, a bio-informatic procedure based on an 'electronic Northern' approach was established to screen expressed sequence tag (EST) libraries for genes differentially expressed in tumour and normal tissues, and identified 450 candidate genes differentially expressed in breast and ovarian cancer. In this report, the validation of an initial set of 40 candidate genes, which were selected due to their localization in chromosomal regions frequently altered in gynaecological tumours, is described. Differential expression of 29 of these genes, including three uncharacterized novel genes, was confirmed by applying cancer profiling arrays with 106 matched pairs of tumour/normal cDNAs and quantitative reverse transcription-polymerase chain reaction (RT-PCR) on 60 clinical specimens. The majority of these differentially expressed genes have not been described previously in the context of breast and ovarian cancer, and may constitute novel diagnostic markers for these tumour entities.

Breast Neoplasms↗
PubMed2005

Continuous low-dose GM-CSF as salvage therapy in refractory recurrent breast or female genital tract carcinoma.

Granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]) is a powerful cytokine that is able to stimulate the generation of dendritic cells. Adjuvant treatment with continuous low-dose GM-CSF has been shown to prolong survival of stage III/IV melanoma patients. Data on continuous low-dose GM-CSF therapy in tumors other than prostate cancer are still lacking. This pilot trial was initiated in order to evaluate the efficacy and tolerability of continuous low-dose GM-CSF as salvage in various chemotherapy-refractory carcinomas. A total of 19 patients who had failed a median of 4 prior chemotherapies were included. Their malignancies included metastatic breast cancer, recurrent ovarian carcinoma, metastatic endometrial carcinoma, and recurrent squamous cell cancer of the cervix uteri. Continuous low-dose GM-CSF was delivered subcutaneously at a daily starting dose of 125 microg. GM-CSF was increased at 25-microg increments until a maximum of 250 microg was reached or when mild leukocytosis (10-20 g/L) was achieved, providing that the relative eosinophil count did not exceed 15%. Therapy was continued until progression or refusal by the patient. Toxicity was generally mild. Only one patient was withdrawn due to grade 3 fatigue. In three additional patients, temporary dose reduction was necessary because of grade 1 injection site reactions, which recovered spontaneously. Mild to moderate leukocytosis was obvious in 10 patients. Systemic hypersensitivity-like reactions did not occur and no patient required hospitalization for other life-threatening side effects. The objective response rate was 37%: 1 complete and 6 partial responses, 4 disease stabilizations, 8 progression of disease. Median response duration was 6 months. Notably, 6 of 7 responders but only 1 of 8 patients with disease progression developed leukocytosis during therapy. Therefore, we conclude that continuous low-dose GM-CSF has substantial activity in heavily pretreated patients with either metastatic breast cancer or female genital tract cancer. Achievement of mild leukocytosis seems to be a predictor of response.

Breast Neoplasms↗
PubMed2004

Limited relevance of the CHEK2 gene in hereditary breast cancer.

To establish the importance of CHEK2 mutations for familial breast cancer incidence in the German population, we have screened all 14 of the coding exons in 516 families negative for mutations in both the BRCA1 and BRCA2 genes. We found 12 distinct variants in 30 unrelated patients (5.81%), including 5 that are novel and an additional 4 found for the first time in breast cancer. These aberrations were evaluated in 500 healthy women aged over 50 years and in the case of the 2 exon 10 mutations, 1100delC and 1214del4bp, in 1315 randomized healthy controls. According to our results, a statistically significant association for the exon 10 mutations was observed (p = 0.006). The prevalence of the 1100delC mutation in the German population, however, is significantly lower than those reported for other Caucasian populations both in familial breast cancer patients (1.6%) and controls (0.5%), and shows independent segregation with breast cancer in 2 of 4 families analyzed. The remaining 10 variants were more abundant in patients (21) compared to the controls (12) although the difference was not statistically significant. Interestingly, we found no increased breast cancer risk associated with the splice site mutation IVS2+1G-->A or the most common missense mutation I157T, which account for more than half (12/21) of the variants observed in patients. The low prevalence and penetrance of the exon 10 deletion mutations together with no, or an uncertain elevation in risk for other CHEK2 mutations suggests a limited relevance for CHEK2 mutations in familial breast cancer. Further evaluation of the unique variants observed in breast cancer is required to determine if they may play a role in a polygenic model of familial breast cancer. Nevertheless, it seems premature to include CHEK2 screening in genetic testing.

Breast Neoplasms↗
PubMed2003

Chromosomal region 15q21.1 is a frequent target of allelic imbalance in advanced breast carcinomas.

Allelic imbalance constitutes a major mechanism of genetic aberrations in breast cancer and strongly indicates the involvement of tumor associated genes in the affected chromosomal regions. Preliminary results from our study indicated the existence of a tumor suppressor gene located on chromosomal arm 15q which may be involved in breast cancer progression.1 In the present study, 210 primary breast carcinomas, 30 metastases and 26 local recurrences from primary breast carcinomas have been analyzed with a panel of 18 highly polymorphic microsatellite markers spanning the chromosomal region 15q11-21.3. Allelic imbalance at 15q with at least 1 marker was seen in 36 of 56 (64.3%) metastases and recurrences, but only in 58 of 210 (27.6%) primary tumors (p<0.0001). We identified a subregion defined by microsatellite marker CYP19 (15q21.1) that showed significantly higher frequencies of allelic imbalance in metastases and recurrences (57.6%) when compared to primary carcinomas (8.9%; p<0.0001). Allelic imbalance at 15q was correlated with histopathologic parameters of the patients with primary breast carcinomas. We detected a significant association with established predictors of poor prognosis, i.e., negative estrogen receptor status (p=0.003), negative progesterone receptor status (p=0.028), high grade (p=0.014) and positive axillary lymph nodes (p=0.013). In summary, our data provide further evidence for a novel prognostic marker in breast carcinomas located in the chromosomal region 15q21.

Alleles↗