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Purpose The Dutch MRI Screening Study on early detection of hereditary breast cancer started in 1999. We evaluated the long-term results including separate analyses of BRCA1 and BRCA2 mutation carriers and first results on survival. Patients and Methods Women with higher than 15% cumulative lifetime risk (CLTR) of breast cancer were screened with biannual clinical breast examination and annual mammography and magnetic resonance imaging (MRI). Participants were divided into subgroups: carriers of a gene mutation (50% to 85% CLTR) and two familial groups with high (30% to 50% CLTR) or moderate risk (15% to 30% CLTR). Results Our update contains 2,157 eligible women including 599 mutation carriers (median follow-up of 4.9 years from entry) with 97 primary breast cancers detected (median follow-up of 5.0 years from diagnosis). MRI sensitivity was superior to that of mammography for invasive cancer (77.4% v 35.5%; P < .00005), but not for ductal carcinoma in situ. Results in the BRCA1 group were worse compared to the BRCA2, the high-, and the moderate-risk groups, respectively, for mammography sensitivity (25.0% v 61.5%, 45.5%, 46.7%), tumor size at diagnosis ≤ 1 cm (21.4% v 61.5%, 40.9%, 63.6%), proportion of DCIS (6.5% v 18.8%, 14.8%, 31.3%) and interval cancers (32.3% v 6.3%, 3.7%, 6.3%), and age at diagnosis younger than 30 years (9.7% v 0%). Cumulative distant metastasis-free and overall survival at 6 years in all 42 BRCA1/2 mutation carriers with invasive breast cancer were 83.9% (95% CI, 64.1% to 93.3%) and 92.7% (95% CI, 79.0% to 97.6%), respectively, and 100% in the familial groups (n = 43). Conclusion Screening results were somewhat worse in BRCA1 mutation carriers, but 6-year survival was high in all risk groups.

Purpose Sentinel node (SN) status is the most important prognostic factor for overall survival (OS) for patients with stage I/II melanoma, and the role of the SN procedure as a staging procedure has long been established. However, a less invasive procedure, such as ultrasound (US) -guided fine-needle aspiration cytology (FNAC), would be preferred. The aim of this study was to evaluate the accuracy of US-guided FNAC and compare the results with histology after SN surgery was performed in all patients. Patients and Methods Four hundred consecutive patients who underwent lymphoscintigraphy subsequently underwent a US examination before the SN procedure. When the US examination showed a suspicious or malignant pattern, patients underwent an FNAC. Median Breslow thickness was 1.8 mm; mean follow-up was 42 months (range, 4 to 82 months). We considered the US-guided FNAC positive if either US and/or FNAC were positive. If US was suggestive of abnormality, but FNAC was negative, the US-guided FNAC was considered negative. Results US-guided FNAC identified 51 (65%) of 79 SN metastases. Specificity was 99% (317 of 321), with a positive predictive value of 93% and negative predictive value of 92%. SN-positive identification rate by US-guided FNAC increased from 40% in stage pT1a/b disease to 79% in stage pT4a/b disease. US-guided FNAC detected SN tumors more than 1.0 mm in 86% of cases, SN tumors of 0.1 to 1.0 mm in 46% of cases, and SN tumors less than 0.1 mm in 23% of cases. Estimated 5-year OS rates were 92% for patients with negative US-guided FNAC results and 51% for patients with positive results. Conclusion US-guided FNAC of SNs is highly accurate. Up to 65% of the patients with SN-positive results in our institution could have been spared an SN procedure.

Purpose To compare the efficacy and safety of doxorubicin and docetaxel (AT) with fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients (n = 216) were randomly assigned to either AT (doxorubicin 50 mg/m2 and docetaxel 75 mg/m2) or FAC (fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2); both regimens were administered on day 1, every 3 weeks. Results A median number of six cycles was delivered in both arms, with a median relative dose-intensity of more than 98%. Median time to progression (TTP) and median overall survival (OS) were significantly longer for patients on AT compared with FAC (TTP: 8.0 v 6.6 months, respectively; P = .004; and OS: 22.6 v 16.2 months, respectively; P = .019). The overall response rate (ORR) was significantly higher in patients on AT compared with FAC (58% v 37%, respectively; P = .003). The ORR on AT was also higher in patients with visceral disease compared with FAC patients with visceral disease (59% v 36%, respectively; P = .003). There were no differences in grade 3 to 4 neutropenia and infections (AT 89% v FAC 84% and AT 12% v FAC 9%, respectively). Neutropenic fever was more common in AT-treated patients than FAC-treated patients (33% v 9%, respectively; P < .001). Grade 3 to 4 nonhematologic toxicity was infrequent in both arms. Congestive heart failure was observed in 3% and 6% of patients on AT and FAC, respectively. Conclusion In this phase II to III study, AT resulted in a significantly longer TTP and OS and a higher objective ORR than FAC. First-line AT is a valid treatment option for patients with MBC.

PURPOSE To analyze the putative relationship between immunotherapy-associated dysthyroidism and the probability of a tumor response. PATIENTS AND METHODS A total of 89 consecutive patients with advanced cancer were treated with interleukin-2 (IL2)-based immunotherapy in a prospective study. RESULTS Twenty patients developed thyroid dysfunction. Repeatedly positive tests for thyroid antibodies developed in 28% of the patients. Twenty-two patients achieved a response. There was no relationship between the formation of antibodies and the probability of response. There appeared to be a trend toward a relationship between thyroid dysfunction and response (P = .23). A strong relationship was found between response on the one hand and cumulative dose of IL2 (P = .01) and treatment duration with IL2 (P = .025) on the other. The frequency of thyroid dysfunction was also significantly correlated with treatment duration (P = .001). After adjustment for cumulative dose of IL2 and treatment duration, no relationship between thyroid dysfunction and response remained (P = .99). CONCLUSION There is no relationship between thyroid dysfunction and the probability of tumor response. Thyroid dysfunction is merely a function of treatment duration and cumulative dose of IL2.

1014 Background: Treatment with trastuzumab and chemotherapy has improved the outcome of HER2-positive MBC. It is unknown what the outcome and toxicity is of monotherapy trastuzumab, followed by chemotherapy at progression, as compared to the combination of chemotherapy/trastuzumab. Methods: HER2-positive MBC pts., being eligible for first line chemotherapy were randomised between combination treatment docetaxel (TAX) (100 mg/m2, q3wks)/trastuzumab (HER) (loading dose 4mg/kg, whereafter weekly 2mg/kg) (arm A) or monotherapy HER, followed upon progression by TAX (similar doses as arm A) (arm B). Further in- /exclusion criteria were adjuvant non-taxoid chemotherapy allowed, previous HER treatment not; normal ejection fraction (EF), adequate liver/renal functions and bone marrow reserve. Primary endpoint was PFS, secondary endpoints: response rate (RR), overall survival (OS) and toxicities. Kaplan-Meier curve was tested by log-rank test, RR by Pearson χ2-test. Results: Of the 101 randomly selected patients, ...

8005 Introduction: The SN procedure has become a widely used staging procedure for stage I/II melanoma patients. We previously reported on the high SN+ identification rate with the use of the EORTC MG group pathology protocol (van Akkooi et al., Eur J Cancer: 2006, in press). Because only approximately 20% of SN positive patients have additional non-SN lymph node involvement in the cLND specimen, we have proposed to identify a SN+ patient group, which can be spared a cLND. Therefore further microanatomic analyses of the metastatic SNs has been performed to identify patient/tumor or SN factors which predict DFS and OS as well as additional non-SN nodal positivity. Methods: 262 stage I/II pts were included into the SN database between 10/97 and 5/04. 77 were SN+ (29%). 74 pts had SN material for re-evaluation in this study. Microanatomic analysis categorized a.o. the location of tumor cells; subcapsular, parenchymal (or combined), multifocal or extensive; the Starz classification and the measurement of the amount of tumor load (in mm). Tumor load was quantified by size: 1.0mm. DFS, OS and additional non-SN positivity was calculated for all the microanatomic analyses. Results: Mean/Median Breslow was 3.5/3.0 (0.8 - 12.0) mm, mean/median FU was 35/30 (6 - 81) months. There were no signif. differences in OS or additional non-SN positivity for the different loc. of involvement. The estimated 5yr OS rates were 100%, 63% and 35% for the different groups of tumor load, 1.0mm respectively (Figure)(P=0.03). There were no patients with add. non-SN positivity in the group with involvement No significant financial relationships to disclose.