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      Der Einfluß von Ovulationshemmern auf die Tumorbiologie und die Prognose des Mammakarzinoms

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          Abstract

          Der Einfluß von Ovulationshemmern auf die Tumorbiologie und die Prognose des Mammakarzinoms Die Frage eines potentiellen Einflusses von Ovulationshemmern (OH) auf die Tumorbiologie und die Prognose des Mammakarzinoms stellt noch immer ein ungeklärtes Problem dar. Zur Untersuchung dieser Frage wurde eine Fall-Kontroll-Studie aufgelegt, die den Effekt der OH-Einnahme vor der Diagnose des Mammakarzinoms auf dessen Prognosefaktoren und den Verlauf der Erkrankung untersucht. Das mediane Follow-up belief sich auf 10 Jahre. Bei 471 Patientinnen wurde der Einfluß von OH auf konventionelle (Tumortyp, Grading, Tumorgröße, LK-Status, ER, PR) und molekularbiologische (PCNA, EGF-R, c-erbB-2, p53) Prognosefaktoren dargestellt. In Abhängigkeit von der Zeit seit der letzten Einnahme von OH konnten 2 Tumorentitäten charakterisiert werden. Bei OH-Einnahme bis zum Zeitpunkt der Diagnose fanden sich signifikant häufiger LK-positive (OR 2.14), schlecht differenzierte (OR 2.01) und stark proliferierende Tumoren (OR 2.13). Patientinnen mit langer Latenzperiode seit letzter OH-Einnahme zeigten signifikant häufiger ER-positive (OR 21.6-3.69) allerdings auch EGF-R-positive Tumoren (OR 1.73-2.0) mit moderater Proliferationsaktivität (OR 1.64-1.93). In multivaraiaten Überlebensanalysen hatten Patientinnen mit Langzeiteinnahme (mehr als 5 Jahre) und solche mit OH-Einnahme lange vor der Diagnose der Erkrankung (mehr als 96 Monate) ein signifikant besseres Überleben (HR 0.55, 95%CI 0.34-0.90; HR 0.49, 95%CI 0.26-0.92 respektive)als Patientinnen ohne OH-Einnahme. Dagegen hatte Patientinnen bei OH-Einnahme bis zur Diagnose oder Einnahme in den letzten beiden Jahren vor Diagnose ein signifikant schlechteres Überleben als solche ohne OH-Einnahme (HR 2.29, 95%CI 1.02-5.17; HR 3.80, 95%CI 1.45-9.97 respektive). Offenbar ist die OH-Einnahme während eines biologisch sensiblen Zeitraumes der Entwicklung des Mammakarzinomes von größerer Bedeutung als die Dauer der OH-Einnahme. Eine biologische Hypothese wird dargestellt.

          Abstract

          Oral contraceptive use and breast cancer: Effect on tumorbiolgy and prognosis The question of whether oral contraceptive(OC) use before diagnosis has an effect on tumorbiology and prognosis of breast cancer remains a subject of discussion. Thus, a case-control study was conducted to investigate the effect of OC use on prognostic factors and the outcome of breast cancer patients. The median follow-up amounted to 10 years. In 471 breast cancer patients histomorphological (tumortype, grading, tumorsize, nodal status, ER, PR) and molecularbiological prognostic factors (PCNA, EGF-R, c-erbB-2, p53) and their association to OC use were studied. 297 (63%) patients were OC users, 113 were short-term users (less than 5 years) and 184 were long-term users. Dependend on the time since last OC use, two different biological tumor entities were characterised. In current users a significant increase in node-positive (OR 2.14) and poorly differentiated tumors (OR 2.01) and of tumors with a high proliferative fraction (OR 2.13) was observed. Past users with a long latency period had significantly more ER-positive (OR 2.16-3.69) but also EGF-R positive tumors (OR 1.73-2.0) with a moderate increase in proliferative activity (OR 1.64-1.93) compared to never users. In multivariate survival analyses long-term OC use (HR 0.55, 95%CI 0.34-0.90) and first OC use more than 96 months before diagnosis (HR 0.49, 95%CI 0.26-0.92) were associated with a significant improvement in survival, whereas current OC use ( HR 2.29, 95%CI 1.02-5.17) or last OC use during the last 2 years before diagnosis (HR 3.80, 95%CI 1.45-9.97) were related to a significant decrease in survival rates. OC use during a biologically sensitive time period seems to be more important than duration of use. A biological hypothesis is beeing suggested.

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            Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms.

            Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle. A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells. In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated. These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation. However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost. In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours. The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression.
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              The relation between survival and age at diagnosis in breast cancer.

              We analyzed the relation between age at diagnosis and relative survival (ratio of observed to expected survival) in 57,068 women in Sweden in whom breast cancer was diagnosed in 1960 to 1978 (about 98 percent of all cases). Women who were 45 to 49 years old had the best prognosis, with a relative survival exceeding that of the youngest patients (less than 30 years) by 7.6 to 12.9 percent at different periods of observation. Relative survival declined markedly after the age of 49--particularly in women aged 50 to 59--and the oldest women (greater than 75) had the worst rate. The difference in relative survival between those older than 75 and those 45 to 49 increased from 8.6 percent at 2 years to 12.2, 20.3, and 27.5 percent after 5, 10, and 15 years of follow-up, respectively. The long-term annual mortality rate due to breast cancer approached 1 to 2 percent at the premenopausal ages but exceeded 5 percent throughout the period of observation in the oldest age group. An understanding of the biologic basis for the complex relation between age and prognosis might provide a better understanding of the natural history of breast cancer in women.
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                Author and article information

                Journal
                Medizinische Fakultät - Universitätsklinikum Charité, Humboldt-Universität (kvv )
                9 January 2001
                31 July 2002
                Affiliations
                [1 ] Medizinische Fakultät
                Article
                oai:HUBerlin.de:20036

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