Wolfram Jäger

Epithelial Cells in Bone Marrow of Breast Cancer Patients at Time of Primary Surgery: Clinical Outcome During Long-Term Follow-Up

PURPOSEnTo evaluate the detection of epithelial cells in bone marrow of breast cancer patients as an indicator of metastatic disease.nnnPATIENTS AND METHODSnBetween 1989 and 1994, bone marrow biopsies were performed on 393 breast cancer patients during primary surgery. Specimens were stained immunocytochemically for epithelial cells expressing cytokeratins or the epithelial membrane antigen. The long-term outcomes of these patients were analyzed in this study.nnnRESULTSnIn 166 of 393 patients, epithelial cells were found in bone marrow (BM) aspirates. These patients were designated BM+. The rate of tumor recurrence or cancer-related death was significantly higher in BM+ patients than in BM- patients. Multivariate analysis using the Cox regression model revealed BM status as a prognostic parameter independent of tumor size and axillary lymph node status. However, tumor size and axillary lymph node status were clearly superior prognostic parameters.nnnCONCLUSIONnDisseminated epithelial cells in BM are associated with poor clinical outcome in breast cancer patients. However, the presence of these cells is not a sufficient parameter to predict growing metastases in the majority of patients, suggesting that epithelial cells in the BM of breast cancer patients at the time of surgery have limited metastatic potential. The role of these cells needs to be further evaluated.

Elevated levels of CA-125 in serum of patients suffering from ovarian hyperstimulation syndrome

Elevated levels of CA-125, an antigen expressed by malignant ovarian tissue, have been found in women who developed OHSS in response to treatment with exogenous gonadotropins for IVF. In contrast, CA-125 concentrations in women who were treated with an identical regimen but who did not show signs of OHSS remained in the normal range. We conclude that the expression of CA-125 is not restricted to neoplastic ovarian tissue but can also occur as a consequence of supraphysiologic stimulation of the ovary with exogenous gonadotropins.

Tumor Size, Axillary Lymph Node Status and Steroid Receptor Expression in Breast Cancer: Prognostic Relevance 5 Years after Surgery

Tumor size, axillary lymph node status and expression of steroid receptors are well-established prognostic factors in breast cancer. However, it is not clear if these prognostic factors are time-dependent variables and lose their significance after several years of disease-free survival. To analyse how long these factors keep their prognostic relevance survival of 1162 breast cancer patients was analysed retrospectively. The post-operative follow-up period was split into consecutive 2-year intervals and each interval was analysed for rate of recurrence and rate of tumor depending deaths. Furthermore, a multivariate analysis was performed for the total follow-up time and for the follow-up period starting 5 years after surgery. Multivariate analysis revealed tumor size, axillary lymph node status and estrogen receptor status as independent prognostic parameters. Analysing separately the rate of recurrences and tumor-related deaths during consecutive 2-year intervals, only the tumor size was a constant prognostic parameter, whereas prognostic relevance of lymph node status decreased. Estrogen receptor status associated with favourable prognosis during the first years after surgery changed to an unfavourable prognostic factor 4 years after surgery. To summarize, prognostic factors obtained at the time of surgery can lose their significance with increasing disease-free survival.

CA 125 Elevations in Patients with Malignant Lymphomas

Circulating CA 125 serum levels were measured in 60 patients with several hematological malignancies. Using 35 U/ml as cutoff level, elevated CA 125 concentrations were found in 3 of 18 patients with acute leukemia, 1 of 5 patients with chronic myelocytic leukemia, 2 of 9 patients with Hodgkin’s lymphoma and in 14 of 28 patients with non-Hodgkin’s lymphoma. None of the healthy control group had CA 125 serum levels above 35 U/ml. In patients with malignant lymphoma, elevated CA 125 serum concentrations were associated with abdominal involvement (p < 0.01). 15 of 19 patients with abdominal tumor masses had CA 125 concentrations above 35 U/ml, but only 1 of 18 patients with supradiaphragmatic involvement. Serial determinations of CA 125 were performed in 3 patients with malignant lymphoma during chemotherapy. Disease regression was associated with decreasing CA 125 serum levels. Thus, CA 125 may be a useful indicator of abdominal involvement in patients with malignant lymphoma. Moreover, serial CA 125 measurement may be of value in monitoring response to chemotherapy in these patients.

Prediction of axillary lymph node status of breast cancer patients by tumorbiological factors of the primary tumor.

Background and Purpose:The increasing use of systemic adjuvant therapy even in lymph node-negative breast cancer patients and breast cancer screening programs detecting smaller tumors with less probability of metastatic lymph nodes questions the need for routine axillary lymph node dissection. Since morbidity of breast cancer surgery is predominantly related to axillary lymph node dissection, predictive models for lymph node involvement may provide a way to avoid lymph node surgery and its side effects in subgroups of patients.Patients and Methods:Using a multivariate logistic regression model, tumorbiological parameters such as expression of estrogen and progesterone receptors, Ki-67, p53, cathepsin D, HER2, S-phase fraction, and ploidy were analyzed regarding their ability to predict axillary lymph node involvement in 655 breast cancer patients.Results:The model correctly predicted axillary lymph node metastases in 58% of the patients by including expression of progesterone receptor, HER2, and Ki-67. In a subgroup of 200 patients predicted to be at extremely high or extremely low risk for axillary lymph node metastases, the accuracy of the prediction was 70%.Conclusion:With a model just based on tumorbiological parameters obtained in the primary tumor it is possible to predict axillary lymph node status. By including additional parameters it appears to be feasible to further improve the model in order to avoid axillary lymph node surgery in low-risk women.Hintergrund und Ziel:Die zunehmende Anwendung adjuvanter Therapien auch bei nodal negativen Mammakarzinompatientinnen sowie die im Rahmen von Screeningprogrammen immer frühzeitigere Entdeckung kleiner Mammakarzinome mit geringer Wahrscheinlichkeit einer axillären Lymphknotenmetastasierung stellen den Nutzen der axillären Lymphonodektomie zunehmend in Frage. Da die axilläre Lymphonodektomie maßgeblich für die Morbidität der Mammakarzinomoperation verantwortlich ist, stellt sich die Frage, ob das Risiko eines axillären Lymphknotenbefalls für Subgruppen von Mammakarzinompatientinnen präoperativ vorhergesagt werden kann.Patienten und Methodik:Mit Hilfe einer multivariaten logistischen Regression wurden tumorbiologische Parameter (Expression von Östrogen- und Progesteronrezeptoren, Ki-67, p53, Cathepsin D, HER2, S-Phasen-Anteil, Ploidie) in Bezug auf ihre Vorhersagekraft für den axillären Lymphknotenstatus bei 655 Patientinnen mit primärer Mammakarzinomerkrankung untersucht.Ergebnisse:Das Modell konnte in 58% der Fälle bei Einschluss von Progesteronrezeptorexpression, HER2 und Ki-67 den Nodalstatus korrekt vorhersagen. Für die 200 Patientinnen, deren Risiko als besonders hoch vorhergesagt wurde, lag die Rate von richtig positiven Befunden bei 70%.Schlussfolgerung:Modelle, die sich lediglich auf tumorbiologische Faktoren des Primärtumors stützen, können unabhängig von klinischen Stagingparametern den axillären Lymphknotenstatus vorhersagen. Durch Erweiterung auf zusätzliche Faktoren ließe sich so ein Modell entwickeln, auf dessen Grundlage bei Frauen mit geringem Risiko für eine axilläre Metastasierung auf die axilläre Lymphonodektomie verzichtet werden könnte.

Lokalrezidivrisiko bei Patientinnen mit brusterhaltender Therapie und Karzinom bis zum Resektionsrand

Patienten und Methode: Von 1790 Patientinnen, die zwischen 1976 und 1986 mit einem Mammakarzinom Stadium I oder II brusterhaltend operiert und nachfolgend bestrahlt wurden, konnten 340 Patientinnen im Sinne der Fragestellung ausgewertet werden. Es wurde unterschieden, ob die Karzinome ausgedehnte In-situ-Anteile enthielten und ob diese den Resektionsrand erreichten. Dabei wurde zus/~tzlich der Abstand zum Resektionsrand unterteilt in weniger und mehr als 1 ram. Ergebnisse: Die Lokalrezidivrate lag bei allen Patientinnen mit Resektion in sano zwischen 2% (<1 ram) und 3% (>1 mm) nach ftinf Jahren. Bei Patientinnen mit intraduktalem Karzinom am Resektionsrand lagen die entsprechenden Rezidivraten zwischen 9% (geringe Ausbreitung) und 28% (ausgedehnte Ausbreitung). Im gleichen Zeitraum entwickelten insgesamt 82 Patientinnen (25%) Fernmetastasen, unabhfingig vom Ausmal3 des intraduktalen Karzinoms, aber abh~ingig vom AusmaB der metastatisch befallenen axill~xen Lymphknoten.