Reliability and validity of needle biopsy evaluation of breast-abnormalities using the B-categorization--design and objectives of the Diagnosis Optimisation Study (DIOS).

BACKGROUND: The planned nationwide implementation of mammography screening 2007 in Germany will increase the occurrence of mammographically detected breast abnormalities. These abnormalities are normally evaluated by minimal invasive core biopsy. To minimize false positive and false negative histological findings, quality assurance of the pathological evaluation of the biopsies is essential. Various guidelines for quality assurance in breast cancer diagnosis recommend applying the B-classification for histopathological categorization. However, to date there are only few studies that reported results about reliability and validity of B-classification. Therefore, objectives of our study are to determine the inter- and intraobserver variability (reliability study) and construct and predictive validity (validity study) of core biopsy evaluation of breast abnormalities. This paper describes the design and objectives of the DIOS Study. METHODS/DESIGN: All consecutive asymptomatic and symptomatic women with breast imaging abnormalities who are referred to the University Hospital of Halle for core breast biopsy over a period of 24 months are eligible. According to the sample size calculation we need 800 women for the study. All patients in the study population underwent clinical and radiological examination. Core biopsy is performed by stereotactic-, ultrasound- or magnetic resonance (MR) guided automated gun method or vacuum assisted method. The histopathologic agreement (intra- and interobserver) of pathologists and the histopathologic validity will be evaluated. Two reference standards are implemented, a reference pathologist and in case of suspicious or malignant findings the histopathologic result of excision biopsy. Furthermore, a self administrated questionnaire which contains questions about potential risk factors of breast cancer, is sent to the participants approximately two weeks after core biopsy. This enables us to run a case-control-analysis (woman with breast cancer histological verified after excision are defined as cases, woman without malignant breast lesions are defined as controls) to investigate the predictive values of various risk factors on breast cancer risk. CONCLUSION: The analysis of reliability and validity of the histopathological evaluation of core biopsy specimens of breast abnormalities is intended to provide important information needed for a high quality in breast cancer diagnostic and for planning of treatment strategies.

CHAMP: A Phase II Study of Panitumumab With Pemetrexed and Cisplatin Versus Pemetrexed and Cisplatin in the Treatment of Patients With Advanced-Stage Primary Nonsquamous Non-Small-Cell Lung Cancer With Particular Regard to the KRAS Status.

INTRODUCTION: The aim of the study was to investigate the efficacy and tolerability of panitumumab, a fully human antiepidermal growth factor receptor monoclonal antibody, in combination with pemetrexed/cisplatin in patients with stage IIIB to IV primary nonsquamous non-small-cell lung cancer and wild type V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). Results were compared with those obtained in a control group of patients who received a pemetrexed/cisplatin regimen only. PATIENTS AND METHODS: This was a phase II, randomized, open-label study with 2 treatment arms. In total, 96 patients received panitumumab at a dose of 9 mg/kg in combination with pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) (n = 49) or pemetrexed/cisplatin alone (n = 47). The primary outcome measure was progression-free survival at 6 months. Secondary end points of the study included overall survival, tumor response, quality of life, and safety outcomes. The CHAMP study is registered with ClinicalTrials.gov, number NCT01088620. RESULTS: Progression-free survival at 6 months did not indicate a benefit of panitumumab as a supplement to the standard therapy of pemetrexed/cisplatin whereas the overall survival showed a clear difference between the treatment groups in favor of the standard therapy. Results might be affected by the higher rates of serious adverse events and higher death rates within the panitumumab arm. CONCLUSIONS: Results from the present study indicate that combination of cisplatin/pemetrexed with panitumumab should not be recommended for patients with adenocarcinoma and KRAS wild type because of lack of efficacy, lack of improvement of quality of life, and because of the increase in toxicity rates compared with patients in the control arm, who received standard chemotherapy of pemetrexed/cisplatin.

Histological category and expression of hormone receptors in ductal carcinoma in situ of the breast.

BACKGROUND: While the role of estrogen receptor (ER) and progesterone receptor (PR) status in invasive breast cancer has been clinically established, data with respect to their role in ductal carcinoma in situ of the breast (DCIS) are sparse. PATIENTS AND METHODS: We reviewed 120 consecutive patients with DCIS I-III. Detailed histological categorization and immunohistochemical staining for ER and PR were performed and correlated with clinical data. RESULTS: DCIS I, DCIS II, and DCIS III were found in 51, 36 and 33 patients, respectively. Comedo-type tumors (p<0.001), presence of tumor necrosis (p<0.001) and absence of ER (p=0.005) were significantly associated with poorly-differentiated DCIS. No association was ascertained between PR expression and grade of DCIS. Hormone receptor expression was independent of the patients' menopausal status. CONCLUSION: We support the assumption that DCIS I-III is morphologically and biologically heterogeneous. Our results contribute further data on the role of ER and PR in the pathogenesis and progression of DCIS.