The ligands, receptors and related signaling proteins of the insulin‐like growth factor family are involved in the regulation of breast‐cancer cell growth. We investigated the expression pattern of insulin‐like growth factor‐I receptor (IGF‐IR), insulin receptor (IR) and insulin receptor substrate‐1 (IRS‐1), a core downstream signaling protein, in 69 primary breast‐cancer specimens of different grades and in 21 control tissues by immunohistochemistry. In addition, cell proliferation (percentage of Ki67+ nuclei) and estrogen receptor (ER) expression were determined. IGF‐IR, IRS‐1 and IR were expressed mainly in epithelial cells. IRS‐1 and IGF‐IR were expressed at high levels in control tissues and in well and moderately differentiated carcinomas but at low levels in poorly differentiated breast cancers. IR expression did not show a significant correlation with the differentiation grade of the tissues investigated. Statistical analysis (ROC analysis for tumor grade) demonstrated that down‐regulation of IGF‐IR and IRS‐1 correlated better with tumor progression than reduction of ER expression or increase in cell proliferation, IGF‐IR showing the best correlation, followed by IRS‐1 and, less significant, ER and Ki67. Our findings clearly show that progression of breast cancer is accompanied by a reduction of IGF‐IR/IRS‐1 expression and that IGF‐IR/IRS‐1 expression inversely correlates with high proliferation rate in dedifferentiated breast cancers. The strong correlation of IGF‐IR and IRS‐1 down‐regulation with tumor progression suggests the use of IGF‐IR and IRS‐1 as a novel set of marker proteins for tumor grading. Int. J. Cancer 89:506–513, 2000. © 2000 Wiley‐Liss, Inc.

The objective of this one-institutional study was to determine the number of large-core needle biopsies (LCNB), under threedimensional ultrasound (3D-US) validation, that are sufficient to obtain a reliable histological diagnosis of a sonographically detectable breast lesion. Over an 28-month period, 962 sonographically guided LCNB were performed under 3D-US validation to assess 962 breast lesions. All biopsies were carried out with an automated core biopsy device fitted with 14-gauge (22 mm excursion) needles. Data of 962 biopsied breast lesions were gathered. Surgical follow-up was available for 659 lesions. Breast malignancies were diagnosed by ultrasound-guided LCNB with a sensitivity of 98.2% by performing three cores per lesion. In few cases, the open surgical specimen revealed the presence of invasive carcinomas in contrast to initial LNCB-based classification as ductal carcinomas in situ (DCIS, 11 lesions), lobular carcinoma in situ (one lesion), and atypical ductal hyperpasia (one lesion). Owing to disagreement between classification based on breast-imaging and histological findings, eight of these tumours were subsequently excised. Of the lesions that were removed at the patients' requests despite benign LCNB diagnosis, two were infiltrating carcinoma and one a DCIS. We demonstrate that three 3D-US-guided percutaneous core specimens are sufficient to achieve tissue for a reliable histological assessment of sonographically detectable breast lesions and allow the detection of malignancies with high sensitivity and low rate of false-negative diagnoses.

Background and Objective: Guidelines for the treatment of early-onset breast cancer have been proposed in several countries, but to date, their impact on outcomes is unverified. The objective of this study was to evaluate the association between guideline-adherent versus nonadherent treatment and recurrence-free survival (RFS) and overall survival (OAS) in early-onset breast cancer patients. Methods: A total of 1,778 patients were included in the study, of whom 111 were 35 years or younger and 1,667 were between 36 and 55 years. RFS and OAS were compared between the two groups, with respect to multiple parameters. All survival data were adjusted for tumor characteristics and analyzed with respect to guideline adherence according to the German Step 3 guidelines. Results: Statistically significant differences between the two groups (<35 years, 36–55 years) were observed with regard to breast surgery (p = 0.002) and hormone therapy (p = 0.006). Both groups were treated identically in terms of guideline adherence concerning axillary dissection (p = 0.9), radiation therapy (p = 0.7) and chemotherapy (p = 0.556). Young breast cancer patients whose treatment adhered to guideline recommendations had increased RFS and OAS [RFS: p = 0.030, hazard ratio (HR) 2.95, 95% confidence interval (CI) 1.11–7.83; OAS: p ≤ 0.001, HR 2.92, 95% CI 2.01–4.23]. Conclusion: Guideline-adherent treatment for early-onset breast cancer patients significantly improves OAS and RFS and should therefore be demanded for all patients.

In conclusion, young breast cancer patients still have a poor prognosis. Even after adjustment of the data, OAS and RFS showed a worse prognosis. Normal prognostic factors like tumor size, axillary lymph node involvement, and grading can therefore be not the explanation for the more aggressive disease progress within early onset breast cancer patients.

Die Ziele unserer prospektiven, randomisierten Studie waren es, die Wirksamkeit von Rizinus, die Häufigkeit, mit der Nebenwirkungen auftreten, die mütterlichen und kindlichen Komplikationen und die Akzeptanz der Methode bei den schwangeren Frauen zu untersuchen. MethodeEinschlusskriterien für die Teilnahme an unserer Studie waren eine Schwangerschaftsdauer von mindestens 37 vollendeten SSW und eine Indikation zur Geburtseinleitung. Die Hauptindikationen waren die Terminüberschreitung und der vorzeitige Blasensprung. In nur 9 Fällen lagen andere Indikationen wie nachlassende Kindsbewegungen, suspektes CTG oder Oligohydramnion vor. Diese anderen Indikationen waren gleichermaßen auf beide Gruppen (Einleitung mit Rizinus-Cocktail bzw. mit Prostaglandin E2-Vaginalgel) verteilt.Ausschlusskriterien waren Frühgeburt, HELLP-Syndrom, Mehrlinge, Typ 1-Diabetes, chronische Darmerkrankungen, Zustand nach Operation mit Uterusper-foration, Fieber, V.a. fetale Kompromittierung (z. B. intrauterine Wachstumsretardierung), Alkoholabusus und intrauteriner Fruchttod.