Researchers working with Dr Marcus Schmidt in the Department of Obstetrics and Gynecology at the University Medical Center Mainz have unlocked the key to the immune system's significance in cases of breast cancer, thus identifying its long-neglected role in the prognosis of the disease.
Their research results, published in the renowned Cancer Research journal, show that patients with certain breast tumors have a better prognosis when more immune cells are present in the tumor. These results permitted the scientists to extend the "coordinate system" in case of breast tumors to include the immune system as the third important reference point for the prognosis of this disease, in addition to the long-established prognostic factors of estrogen receptor expression and proliferative activity (Cancer Research, 1 July 2008; Cancer Research, 1 April 2009).
In the past, physicians searched intensively for criteria and factors permitting a reliable conclusion on the prognosis for node-negative breast cancer, that is, where the axillary lymph nodes show no tumour invasion. Two factors were established during numerous studies: estrogen receptor expression and proliferative activity, i.e., the rate of tumor cell division. The more estrogen receptors were detected in a patient, the better the prognosis was. The more proliferative activity there was, i.e., the faster the cells divided, the poorer the prognosis. Whether the prognosis is good or poor depends on the instance of early distance metastases in the liver, lungs, and bones in the first five years.
"However, the system of the two coordinates 'estrogen receptor expression' and 'proliferative activity' was not sufficiently reliable in the prognosis of all tumors," explained Dr Marcus Schmidt, senior physician at the Department for Obstetrics and Gynecology in the University Medical Center of Johannes Gutenberg University Mainz. "Particularly puzzling was a group of tumors that did not generate any early metastases, despite a high rate of proliferation and low estrogen receptor levels - currently considered to be the criteria for a poor prognosis. This could not be explained with the knowledge at hand. Applying a third criterion - the immune system - we can now round out this somewhat incomplete picture of the prognosis for breast cancer to achieve a more conclusive one."
The scientists tracked the immune system using gene expression analysis. With this analysis, a large number of genes can be identified and characterized with respect to their activity in the tumor tissue. "Using this method, we can examine the development of more than 14,500 genes - i.e., their expression," explained Marcus Schmidt. "During these studies on the tissue of 200 patients, we came across a group of genes with which we were able to explain the currently inexplicably good prognosis in the case of a certain group of rapidly dividing tumors. Primarily, we were able to attribute these genes to immune system cells - B cells and T cells. The more of these immune cell transcripts were present, the better the prognosis was - particularly with tumors in which a poor prognosis was expected because of the high rate of proliferation."
To validate and confirm their findings, the researchers of Mainz University examined the data of two other patient groups whose gene expression data had been published and is therefore accessible. The results in both cases were the same as with the Mainz patient group. With this additional data, they had access to the tissue samples of a total of 788 patients. "For us, this confirms that the immune system plays a fundamental role in breast cancer prognosis, and its importance is comparable to that of the tumor cell division rate," explained Marcus Schmidt. "Our research work should consequently draw attention to the long-neglected role of the immune system in breast cancer, expanding on and complementing the currently known factors of estrogen receptor expression and proliferative activity."
In Marcus Schmidt's view, however, the significance of these findings goes beyond improved characterization and prognostic assessment in the case of node-negative breast tumors. For example, the observed protective effect of immune cells, which occur naturally in the tumor in any event, presents a clear case for using the favorable role of the immune system in breast cancer prognosis as additional therapy with inoculation strategies.Marcus Schmidt, Daniel Böhm, Christian von Törne, Eric Steiner, Alexander Puhl, Henryk Pilch, Hans-Anton Lehr, Jan G. Hengstler, Heinz Kölbl and Mathias Gehrmann
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