The goal of the Guideline “Early Detection of Breast Cancer in Germany” is to assist physicians, healthy women, and patients in the decision-making process in favour of appropriate health care regarding early detection and diagnosis of breast cancer. The principle of early detection of breast cancer embraces the detection of non-invasive stages of breast cancer (UICC stage 0, carcinoma in situ), reducing the frequency of invasive breast cancer development, as well as the identification of breast cancer at an early stage (UICC stage I) having a chance of cure of more than 90%, as shown by a large number of trials. The Guideline summarized in the following paper is a precondition to establishing a nation-wide, comprehensive, quality-assurance program for the early detection and diagnosis of breast cancer. The resulting consequence should be a timely mortality reduction of breast cancer. The cure of early stage disease will additionally be achieved by less intensive treatment methods while largely maintaining the quality of life of breast cancer patients. Implementing the Guideline offers the possibility of a significant improvement in women’s health care.

Background: The present analysis focuses on the long term psychological reactions to early stage breast cancer. Two hypotheses were formulated. The first hypothesis draws a direct link between tumour size/survival chances and Quality of life (QoL): The better the survival chances, the better QoL ( ‘biological danger model’ ). The second hypothesis assumes that localized early breast cancer has excellent prognosis (>90% five year survival rate), and that therefore QoL differences between various forms of early breast cancer should be minimal ( ‘medico-pragmatic model’ ). Patients and methods: In a defined rural area with 252.000 inhabitants (small-area-analysis), a total of n = 389 patients with primary breast cancer were recruited. For the present analysis we selected a subgroup (n = 269) from the cohort by tumour size (pTis, pT1a,b, pT1c, and pT2). QoL scores for global quality of life, emotional functioning and future perspective were computed according to the EORTC manual and compared to age-matched norm data of the German population. Results: A total of 690 QoL questionnaires were obtained from n = 269 patients with comparable completion rates within the four subgroups (pTis, pT1a,b, pT1c, and pT2). For all four groups and in all scores there were improvements over time. Generally, pTis always scored highest, pT2 always lowest, the other two groups in between. After one year pTis patients had higher mean scores in global quality of life than the norm. In contrast, pT1a,b were considerably lower than the norm and the difference between these two was 17.2 score points. It seems that the small difference (3.5%) in five year survival chances between pTis and T1 a,b tumours transforms into marked differences regarding quality of life, thus supporting a biological danger model of the survival/QoL relationship. Conclusions: Our results show that physicians have to realise although their early breast cancer patients have excellent survival chances, psychological distress is present. From a clinical perspective we would recommend that early stage breast cancer patients, and especially patients with occult, pT1a,b tumours be informed about their excellent prognosis. In addition, cognitive therapy might help patients stop worrying about their cancer.

588 Background: The role of medical ablation after adjuvant chemotherapy in endocrine sensitive or non-sensitive tumors is not yet clearly defined. Methods: We initiated a prospective, randomized multicenter study comparing goserelin (3.6 mg every 28 days for 2 years) and control after adjuvant chemotherapy consisting of three cycles of CMF (500/40/600 mg/m2, i.v. on days 1, 8 q 29) in patients with 0–3+ lymph nodes (LN) and four cycles of EC (90/600 mg/m2, i.v. day 1 q 22) followed by 3 x CMF in patients with 4–9+ LN. At first only patients with hormone receptor (HR)-negative breast cancer were included. However, the study was extended to patients with HR-positive breast cancer and 1–9+ LN, when the ZEBRA study was closed. Results: 776 patients were included (goserelin: n=384; control: n=392), 60% had negative HR, 40% were LN-, 23% had 4–9+ LN; 30% of the patients were 40 years or younger, and 60% received breast conserving surgery. 215 events were observed after a median follow-up of 4.7 years. The first event of failure (goserelin vs control) was an isolated locoregional recurrence (43 vs 29), a distant failure (59 vs 82) and death without previous recurrence (0 vs 2). Five-year event-free survival rates were 71.3% (95% confidence interval (CI), 66.3% to 76.3%) and 67.6% (95% CI, 62.2% to 73.0%) in the goserelin and in the control group, respectively. The estimated hazard ratio of goserelin vs control was 0.92 (95% CI 0.70 to 1.21; P > 0.5) indicating no long-term benefit of goserelin in these patients. In an analysis restricted to LN+ patients, there was no indication of a differential treatment effect in HR+ as compared to HR- patients. Conclusions: The results of this study do not support the use of a GnRH analogue after adjuvant chemotherapy in premenopausal patients with breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca; Pfizer; Deutsche Krebshilfe

Aim: The syndrome was first described by Poland in 1841. It classically consists of unilateral muscular and osseous anomalies of the thorax and upper limb with defects of the ipsilateral breast and nipple. We report the value of panoramic-sonography in the diagnosis of this rare condition in three patients. Method: The three girls, all born in 1990, were independently introduced to our unit of children and adolescent gynaecology because of unilateral "developmental defects" of the breasts at the beginning of puberty. To discriminate a Poland-Syndrome from unilateral accentuation of thelarche standardized clinical and sonographical examinations were performed. Results: In 2 cases we found unilateral aplasia of the glandular tissue of the breast with different distinction of mamilla and pectoralis muscle. The 3(rd) case showed a hypoplastic breast development with osseous defects of the chest wall, aplasia of the pectoralis muscle and brachydaktylia. Conclusion: The standardized panoramic sonography allowed an immediate and safe diagnosis without hazardous radiation exposure.

AIM:The syndrome was first described by Poland in 1841. It classically consists of unilateral muscular and osseous anomalies of the thorax and upper limb with defects of the ipsilateral breast and nipple. We report the value of panoramic-sonography in the diagnosis of this rare condition in three patients.METHOD:The three girls, all born in 1990, were independently introduced to our unit of children and adolescent gynaecology because of unilateral "developmental defects" of the breasts at the beginning of puberty. To discriminate a Poland-Syndrome from unilateral accentuation of thelarche standardized clinical and sonographical examinations were performed.RESULTS:In 2 cases we found unilateral aplasia of the glandular tissue of the breast with different distinction of mamilla and pectoralis muscle. The 3 (rd) case showed a hypoplastic breast development with osseous defects of the chest wall, aplasia of the pectoralis muscle and brachydaktylia.CONCLUSION:The standardized panoramic sonography allowed an immediate and safe diagnosis without hazardous radiation exposure.

UNLABELLED:Information and education is needed to empower autonomy and self-determination of patients (informed consent). Furthermore reliable and accurate medical information is necessary for patients who want to take an active part in medical decision-making. The aim of this work is to define the requirements helping to assure the development of good qualified information material relevant for women and female patients as "a guideline on women information". An example of its use is given by embeding this guideline in the guideline for early detection of breast cancer in Germany by defining the specific elements required for developing qualified information on this issue for women.METHODS:A systematic, stepwise methodological process according to a level two guideline of the German Association of the Scientific Medical Societies (AWMF) and the Agency for Quality in Medicine (AZQ) was performed with the following elements: 1. Establishing an expert panel, 2. Generating the guideline statements by a formal, consensus based nominal group process, 3. External review process and finding supportive partners for the guideline on women information, 4. Using the guideline for guidelines: implementing the concept in the guideline of early detection of breast cancer in Germany.RESULTS:The "guideline women information" comprises nine elements of quality assuring requirements for the development of gender-specific information material and eleven specific elements which directly relate to the guideline statements on early detection of breast cancer. After external review 30 organisations gave their written support for future implementation of the guideline. The "guideline women information" was integrated as a tool for quality assurance of lay information into the "guideline for early detection of breast cancer in Germany".CONCLUSION:The "guideline women information" is a systematically developed, consensus-based recommendation to improve the development of qualified lay information at the point of its process by defining gender-specific aspects required for good lay information and its evaluation. As a guideline for guidelines its use is demonstrated by integrating this guideline into the "guideline for early detection of breast cancer in Germany" to ensure the development of qualified guideline compliant information.

Klimakterische Symptome belasten Patientinnen mit gynäkologischer Malignomerkrankung nachweislich stärker als andere Frauen. Hormonbehandlungen sind zurückhaltend einzusetzen, solange noch keine prospektiv-randomisierten Studien die Unbedenklichkeit einer Behandlung in Bezug auf rezidivfreies und Gesamtüberleben belegen.

The Aim of this level 3 good clinical practice guideline is to help physicians, women and patients in decision making about the appropriate health care for early detection of breast cancer. The principle of early detection of breast cancer comprise the detection and diagnosis of premalignant breast tumors (stage 0, Carcinoma in situ), risk reduction of cancer development as well as the detection and diagnosis of breast cancer at an early stage (stage I), with a 90% chance of cure as shown by a large number of clinical trials. To establish a nation wide, comprehensive quality assuring program for the early detection of breast cancer the guideline summarized in the following paper offers the basis for a timely mortality reduction of breast cancer. The cure of early stage disease will be additionally possible by less invasive treatment allowing patients to maintain quality of life. The guideline leads to a major improvement of women's health care.

Zielsetzung: Leitlinien werden zunehmend zu einem unverzichtbaren Bestandteil ärztlicher Tätigkeit. Im Zentrum der bisher praktizierten Leitlinienentwicklung standen überwiegend eng umschriebene, fachbegrenzte medizinische Probleme. Der vorliegende Leitlinienreport zur Brustkrebs-Früherkennung in Deutschland beschreibt exemplarisch die methodische Weiterentwicklung einer neuen Generation von Leitlinien, die sich komplexen, multidisziplinären und dabei sektorübergreifenden Gesundheitsproblemen im Rahmen kompletter Versorgungsketten widmen. Methodik: Die methodische Leitlinienentwicklung erfolgt als systematischer Mehrschrittprozess und enthält als neue Elemente: 1. Outcome-Analyse, 2. Patienten Selbstbestimmung und Lebensqualität, 3. Qualitätssicherung der gesamten Versorgungskette unter besonderer Berücksichtigung der fächerübergreifenden Schnittstellen und die Entwicklung von Qualitätsindikatoren, 4. Konsensus zwischen medizinisch-wissenschaftlichen Fachgesellschaften, ärztlichen Berufsverbänden und nicht-ärztlichen Organisationen. Ergebnisse: Das Manual zur Leitlinienerstellung ist unter www.senologie.org/Manual I+II/download.pdf dargestellt. Über folgende Detailergebnisse wird im vorliegenden Report berichtet: Klinischer Algorithmus und evidenzbasierte Medizin (EBM), qualitätsgesicherte Fraueninformation, Methoden der Qualitätssicherung und Entwicklung von Qualitätsindikatoren, methodische Gestaltung und Ablauf der Konsensusverfahren sowie Abstimmungsergebnisse. Schlussfolgerung: Die methodische Mehrschrittentwicklung einer evidenz-, konsensus- und outcome-basierten Leitlinienentwicklung mit Integration von Elementen der Qualitätssicherung unter der Berücksichtigung der gegebenen Strukturen des deutschen Gesundheitssystems ist ein geeignetes Verfahren zur Leitlinienentwicklung für komplexe, multidisziplinäre Versorgungsketten.

OBJECTIVE:The goal of this work was to study the anticancer activity of cetrorelix, a decapeptide with LHRH receptor antagonist properties in patients with platinum-resistant ovarian cancer. About 80% of primary ovarian cancers and cell lines bear LHRH receptors. Cetrorelix has anticancer activity in in vitro and in vivo ovarian cancer models. METHODS:Eligible patients with ovarian or mullerian carcinoma resistant to platinum chemotherapy received cetrorelix 10 mg subcutaneously every day. Eligibility criteria included age > or = 18, PS < or = 2, measurable disease, chemistries and blood counts in normal range, no estrogen replacement for at least 2 weeks, and no known allergic reactions to extrinsic peptide. In patients volunteering for a biopsy, tissue was taken to perform a LHRH receptor assay. RESULTS:Seventeen patients were treated. Median age was 58 years. Median performance status was 0. Median number of prior chemotherapies was 3. Three patients had partial remissions lasting 9, 16, and 17 weeks. Toxicities effects included grade 4 anaphylactoid reaction (one patient) controlled by cortisol and cimetidine, grade 2 histamine reaction (two patients), grade 2 arthralgia (one patient) 20% cholesterol increase (two patients, who did not require specific treatment), minor hot flushes, headache, and local skin reaction at the injection site. Six of seven samples were LHRH receptor positive for mRNA and/or ligand assay. Two responding patients were LHRH receptor positive. The patient who had no receptor did not respond. CONCLUSION:Cetrorelix has activity against ovarian cancer in this refractory population, and has minimal toxicity, except for potential anaphylactoid reactions. Activity may be mediated through the LHRH receptor.

Mammography screening is not synonymous with early detection of breast cancer, but rather the performance and reading of high standard mammograms in an invited target population at higher risk for breast cancer without any physician-patient contact. Quality assurance of mammography is a management plan aiming to optimize the risk-benefit relation of the procedures applied by defining the requirements for technical and personnel standards.Early detection of breast cancer is a comprehensive multidisciplinary and multiprofessional concept of women's health care. Together with treatment and surveillance, it forms a national breast cancer control program. To establish an early breast cancer detection program, systematic highly qualified guidelines on good clinical practice were finalized for Germany according to the national guideline protocol of the Association of the Scientific Medical Societies in Germany (AWMF). The guideline recommendations comprise the full chain of care for early detection and diagnosis of breast cancer and its implementation respecting the specific conditions and resources of the German health care system. Continuous quality improvements of an effective and efficient guideline-compliant net of health care (including breast centers and disease management programs) rely indispensably on data management and its processing within clinical and epidemiological cancer registries.

The present study investigates the population of beta(2)-receptors on lymphocytes in pregnant women with premature labor between the 29(th) and 34(th) week of pregnancy. The population of receptors on lymphocytes correlates with that on the myometrium, which is not accessible for study during pregnancy. Fourteen patients received a pulsatile tocolysis, while ten women received a continuous tocolysis with Fenoterol. Assuming an equal population of receptors in both groups before commencement of therapy, the numbers of receptors in the patients with continuous tocolysis fell to about 35 % of the initial value after 72 hours. Under pulsatile tocolysis, the numbers of receptors remained unchanged for a period of three days and was still only just below 70 % of the initial value by the seventh day. Our data demonstrate that continuous administration of the short-acting beta(2)-agonist Fenoterol resulted in a substantial loss of beta(2)-adrenoceptors on lymphocytes.In contrast, intermittent administration of the same beta(2)-adrenergic agonist prevented the onset of receptor down-regulation in pregnant women with preterm labor.

Zusammenfassung Sowohl endogene als auch exogen zugeführte Hormone haben Auswirkungen auf die Gewebsdichte der weiblichen Brust und somit auf die Sensitivität und Spezifität der Mammographie. Bei intakter Ovarialfunktion sollte eine Mammographie daher in der Follikelphase durchgeführt werden. Auch eine postmenopausale Hormonersatztherapie beeinflusst die Gewebsdichte, insbesondere bei kontinuierlicher kombinierter Gabe von Östrogenen und Gestagenen. Dagegen erhöhen Tibolon und Antiöstrogene die Gewebsdichte nicht. Da bislang nicht geklärt ist, welchen Einfluss eine Verminderung der mammographischen Gewebsdichte auf das Brustkrebsrisiko hat, ist sie als Biomarker in der Prävention des Mammakarzinoms nicht geeignet. Bei der Krebsfrüherkennung ist die individuelle endokrine Situation der Frau in die Bewertung der Befunde mit einzubeziehen. Unklare Befunde bedürfen der weiteren apparativen oder minimal invasiven Abklärung.

Objective Reproductive factors such as parity and breast-feeding may be associated with low bone mass and osteoporotic fractures in later years. In this study, os calcis quantitative ultrasonometry was used to elucidate the relationship between parity, lactation and bone mass in postmenopausal women.Design This was a comparison study using subsequent matched pairs analysis as well as multiple linear regression analysis. The study was carried out at five centers in Germany. The study included 2080 postmenopausal women (age (mean +/- SD) 58.8 +/- 8.2 years), who were attending for routine check-up and in whom diseases and drug treatments known to affect bone metabolism had been excluded.Methods and outcome measures Women underwent quantitative ultrasonometry (QUS) measurement at the heel. Values of the ultrasonometry variables - speed of sound, broadband ultrasound attenuation and stiffness index - were calculated and compared for nulliparous and parous women and for women who had and had not breast-fed. Because of some significant intergroup differences, and to determine any effect of the number of live births and the duration of breast-feeding on ultrasonometry results, second analyses were undertaken using equally sized samples, matched for possible confounding variables such as age and body mass index (matched pairs). In these analyses, nulliparous women were compared with parous women, grouped according to number of live births, and women who had never breast-fed were compared with women who had breast-fed, grouped according to duration of breast-feeding. Furthermore, a multiple linear regression analysis was performed to examine the combined effects of reproductive factors on QUS variables.Results No statistically significant associations were found between ultrasonometry variables and parity or breast-feeding, even after controlling for confounding variables in matched-pairs analysis or in a multiple linear regression analysis.Conclusions Reproductive factors such as parity and breast-feeding are not associated with subsequent low bone mass of the os calcis, assessed by quantitative ultrasonometry in postmenopausal women. Further longitudinal studies are needed to improve our understanding of the mechanism of bone turnover during pregnancy and breast-feeding.