Der Einfluss des Hämoglobinwertes auf die hämatogene Tumorzelldisseminierung zum Zeitpunkt der Primärdiagnose des Mammakarzinoms

Hintergrund und Fragestellung: Dem Serumhämoglobinwert von Tumorpatienten wurde in den letzten Jahren zunehmende Beachtung geschenkt. Ziel dieser Untersuchung war es festzustellen, ob bei Mammakarzinompatientinnen mit einem niedrigeren Serumhämoglobinwert zum Zeitpunkt der Primärdiagnose ein höheres Risiko für eine primäre, hämatogene Disseminierung von Tumorzellen ins Knochenmark besteht als bei Patientinnen mit einem höheren Hämoglobinwert.

Patienten und Methodik: Im Zeitraum von März 1994 bis März 2000 wurde an der I. Frauenklinik der Ludwig-Maximilians-Universität München prospektiv bei 360 konsekutiven Patientinnen (mittleres Alter 57,5 Jahre) mit primärem Mammakarzinom vor Beginn der Primärtherapie eine Knochenmarkpunktion durchgeführt. Gleichzeitig erfolgte die Bestimmung des präoperativen Hämoglobinwertes (g/dl). Der Nachweis isolierter Tumorzellen im Knochenmark wurde mit dem Panzytokeratinantikörper A45-B/B3 erzielt. Das Gesamtkollektiv wurde anhand des medianen Hämoglobinwertes dichotomisiert. Die Patientinnen wurden anschließend im Median 30,7 Monate nachbeobachtet.

Ergebnisse: Der mittlere Hämoglobinwert betrug 13,8 g/dl (Median 13,9 g/dl, Standardabweichung 1,2). Es fand sich kein statistisch signifikanter Unterschied in der Häufigkeit von zytokeratin-positiven Knochenmarkbefunden zwischen den beiden Untersuchungsgruppen: Während bei Patientinnen mit einem präoperativen Hämoglobinwert von ≤ 13,9 g/dl in 28 % der Fälle (n  =  48) disseminierte Tumorzellen im Knochenmark nachgewiesen wurden, so war dies bei 31 % der Patientinnen mit einem präoperativen Hämoglobinwert von > 13,9 g/dl der Fall (n  =  58, p =  0,50). Die mediane Überlebenszeit von Patientinnen mit höherem und niedrigerem Hämoglobinwert unterschied sich nicht signifikant (mediane Überlebenszeit 67,9 vs. 65,8 Monate, p  =  0,46). Zwischen Patientinnen mit und ohne Nachweis von isolierten Tumorzellen im Knochenmark zeigte sich jedoch ein signifikanter Unterschied in der Überlebenswahrscheinlichkeit (59,7 vs. 69,2 Monate, p < 0,0001).

Folgerung: Es besteht derzeit kein Hinweis, dass der präoperative Hämoglobinwert ein prognostischer Faktor für die hämatogene Disseminierung von Tumorzellen und für das Überleben von Patientinnen mit primärem Mammakarzinom ist.

The relationship between haemoglobin concentration and haemotogenous tumour cell dissemination at initial diagnosis of breast cancer

Background and objective: In the last few years special attention has been paid to the serum concentration of haemoglobin in patients with cancer. It was the aim of this study to ascertain whether at the time of the initial diagnosis low haemoglobin levels in patients with breast cancer denote a higher risk of primary haematogenous dissemination of tumour cells in bone marrow than that in those with higher levels.

Patients and methods: Between March 1994 and March 2000 bone marrow aspirates were performed and serum haemoglobin concentrations (g/dl) measured before primary surgical treatment in 360 consecutive patients (mean age 57.5 years) with primary breast cancer. Evidence of isolated tumour cells in bone marrow was obtained with the pancytokeratin antibody A45-B/B3. The cohort was divided into two groups on the basis of mean haemoglobin values, and the patients underwent follow-up examination a mean of 30.7 months after the initial diagnosis. Patients with metastases at first diagnosis or those who had received nonsurgical treatment at that time were excluded.

Results: The mean pre-treatment haemoglobin concentration of the cohort was 13.8 g/dl (median 13.9 g/dl, S.D.1.2). There was no statistically significant difference in the frequency of cytokeratin-positive bone marrow findings between the two groups. While disseminated tumour cells were demonstrated in the bone marrow of 48 (28%) patients with a pre-treatment haemoglobin of ≤ 13.9 g/dl (p = 0.50), this was so in 58 patients (31%) with a pre-treatment haemoglobin of > 13.9 g/dl. There was also no difference between the two groups regarding median survival time (67.9 vs. 65.8 months; p = 0.46). However, there was a significant difference in probability of survival between patients with or without isolated tumour cells in the bone-marrow (59.7 vs. 69.2 months; p < 0.0001).

Conclusion: There is no evidence at present that the preoperative haemoglobin concentration is of prognostic value regarding the haematogenous dissemination of tumour cells and the survival time of patients with primary breast cancer.

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