Breast Cancer: With the Aid of B&T

31. August 2009

A team of researchers has discovered the importance of the immune system for prognosis of mamma carcinomas: If B- and T-lymphocytes are particularly active, the probability of distant metastases occurring is significantly decreased.

Every year about 57,000 women in Germany get breast cancer. Over the last years, early diagnosis programs and improved treatment methods reduced the probability for the disease to end deadly by about 30 percent. Especially if the tumor is limited to the breast and has not affected any of the neighboring lymphatic glands the chances for healing are particularly good. Since breast cancer can spread rapidly in the body some patients developed metastases even after surgery.

So physicians set criteria in order to be in a better position to assess which of heir patients run the risk of developing metastases. In addition to classical criteria such as size of tumor and number of affected lymphatic glands molecular factors are playing a more and more important role. For example patients with tumor cells proliferating fast and only few estrogen receptors normally have a bad prognosis.

Immune cells hamper metastases

Cancer researchers at the Mainz University now succeeded in identifying an additional factor allowing a more reliable prognosis for breast cancer patients without affected lymphatic glands in their armpits. As the team of physicians around Marcus Schmidt reported in the journal Cancer Research, the chances for a patient increases not to get metastases if the tumor tissue contains an increased number of immune cells. Within a retrospective study, Schmidt and his colleagues analyzed tissue samples of 200 breast cancer patients whose lymphatic glands in their armpits were not affected and who had surgeries between 1988 and 1998.

Contrary to today’s practice, they did not receive any additional therapy with drugs afterwards. “This makes the analysis of such a study considerably more easy since the influence of drugs does not have to be taken into consideration”, explains Schmidt. The researchers examined the activities of nearly 2,600 genes in the tumor tissue of the patients. Those were sorted on a chip such as creating clusters representing the various biological processes.

In 95 patients, mostly one cluster of genes showed high activities which are responsible for fast cell proliferation. 28 of those patients developed distant metastases within the following five years. All others were spared from that. “Actually you could have expected that due to the high rate of cell proliferation the majority of the patients would develop metastases”, says Schmidt. “We are asking ourselves why not all patients with rapidly growing cancer cells are sharing the same destiny.”

Gene of B- and T-lymphocytes show high activity

The researchers subsequently discovered that in patients without metastases two additional gene clusters showed an increased activity. Those clusters contain genes which are turned on in immune cells. These genes carry the construction plan for proteins playing an important role in B- and T-lymphocytes like for example immunoglobulin and T-cell receptors. At the moment, Schmidt and his team of researchers are working on identifying those genes.

The physician assumes that the immune cells intrude the tumor tissue and fight cancer cells there. “However, it is utterly unclear why in some patients the immune defense gets active and in others it does not”, says Schmidt. “Just like we do not know how immune cells prevent single tumor cells from separating and starting to wander off into the blood circulation system.”

In order to ensure their results, the scientists in Mainz analyzed an additional two studies which were published previously by other work groups including gene expression data of 588 additional breast cancer patients without affected lymphatic glands in their armpits – both studies showing the same results as the one made by the team in Mainz. “For us this is the confirmation: The status of the immune system has a similarly high informative value for the prognosis of breast cancer as the proliferation rate of the tumor cells”, says Schmidt.

Prospective study is missing

Other experts, however, are requiring an additional study: “Although this is a very interesting analysis, we have to reassess its actual standing within a prospective study with a larger number of patients”, says Professor Manfred Kaufmann, directory at the Klinik für Frauenheilkunde (hospital for gynecology) at the clinical center at Frankfurt University and chairman of the board of trustees of the Deutsche Krebsstiftung (German cancer foundation). Such a study for example could decide whether only those breast cancer patients without involvement of the lymphatic glands and with less active immune cells will be treated with an adjuvant chemotherapy.

Due to the retrospective character of his study, also Schmidt most likely will not recommend any patient to pass a preventive chemotherapy with all its side effects. “Although a surgery is enough to heal about 70 percent of the patients without affected lymphatic glands without any additional therapy,” he says, “but since we are not sure whom we can treat successfully and whom we cannot, we prefer going on the safe side by giving nearly each one of these patients an additional chemotherapy.”

But Schmidt hopes that – by means of his work – algorithms will be developed factoring the status of the immune system into the prognosis. “It has to be our target not only to decrease the number of ‘over’-treated patients but also to develop therapies less rich of side effects,” demands Schmidt. He considers a vaccination stimulating the immune system of breast cancer patients to be one possibility.

Vaccination could avoid chemotherapy

The physician is not out on a limb with his point of view: “An adjuvant vaccination in mamma carcinoma cases might help to reduce the number of applications of chemotherapy with its often dramatic long-term consequences”, says Jalid Sehouli, deputy director at the Klinik für Frauenheilkunde und Geburtshilfe (hospital for gynecology and obstetrics) at the Berlin Charité. Since the present experiments in this field have not shown any really convincing results, both scientists assume that some more time will have to pass before vaccinations against tumor cells will become daily routine in a hospital.

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