June 8, 2005 A test that measures how quickly cells are dividing is an accurate way for doctors to predict the aggressiveness of breast cancer tumors, even among women with very early stages of the disease, researchers told the 2nd ESMO Scientific & Educational Conference (ESEC) in Budapest, Hungary. The findings will help clinicians decide which patients will benefit most from treatment with more intensive chemotherapy.
For most women whose invasive breast cancer is detected early, research shows that prognosis is generally excellent. But the group includes dramatically different subgroups of patients who need to be identified in order to perform the most effective treatment.
Clinicians know that the molecule Ki67 is a good indicator of cell proliferation rate, and the marker is already used to define the aggressiveness of later stages of breast cancer. But it was not clear how effective it would be in very early stages of the disease.
Dr. Monica Gionvannini and colleagues from the University of Verona in Italy analyzed 4,250 patients with early invasive breast cancer and correlated Ki67 levels with tumor size, nodal status, and other parameters.
"We found that high cell proliferation rate, measured as Ki67 levels, correlates with larger tumor size, axillary nodal involvement, higher grading, lymphovascular invasion, ER and PgR negativity, c-erbB2 overexpression, p53 mutation, younger age at diagnosis and symptomatic presentation," Dr. Giovannini said. "All these factors are well known markers of poor prognosis."
The same findings were valid also when the 'pT1' subgroup of the very earliest stage cancers was considered. "This means that very early invasive breast cancer gathers very different tumors in terms of prognosis and Ki67 could be a reliable and easily obtainable marker in order to identify which pT1 have worse prognosis," Dr. Giovannini said.
Commenting on the data, Dr. Ahmad Awada from Jules Bordet Institute, Brussels, Belgium, said the data presented by Dr. Giovannini confirm that Ki67 is a prognostic indicator in early breast cancer. "What is interesting in the analysis is that Ki67 showed the same prognostic indication in small tumors such as pT1."
"Furthermore, in clinical practice, tumors with pathological size of <1cm are a true challenge in term of therapeutic decision (mainly chemotherapy indication). Consequently, it will be important to correlate Ki67 expression and prognostic in these very small tumors (<1 cm), which ultimately could help us to use this 'easy-to-perform' parameter in the selection of therapeutic approach."
GENE LINKED TO LOWER BREAST CANCER RISK
In another presentation at the conference, Dr. Uwe Langsenlehner and colleagues from Medical University Graz in Austria showed that a specific genetic variation in a cytokine gene is associated with lower breast cancer risk.
Cytokines are molecules that act as signals between cells. The authors were examining the cytokine IL 10, which is involved in the development of various tumors.
"In breast cancer risk, IL-10 may be a two-edged sword," Dr. Langsenlehner said. "On one hand, higher IL-10 levels could facilitate development of cancer by supporting tumor escape from the immune response. On the other hand, the anti-angiogenic effects of IL-10 are supposed to prevent or reduce tumor growth and spread."
Specifically, the Austrian team examined a particular genetic arrangement, or haplotype, in the promoter region of the gene, which has been associated with increased IL-10 expression. The researchers call this the TCATA haplotype.
In a study comparing 500 women with breast cancer against 500 health controls, they found that breast cancer patients were significantly less likely to have two versions of the TCATA haplotype.
"Our study suggests that high levels of IL-10 may be protective against breast cancer," Dr. Langsenlehner said. "The mechanism for this remains to be determined, but may likely include anti-angiogenic functions of IL-10. If this result can be confirmed in additional studies, determination of IL 10 genotypes may help to obtain a more precise individual breast cancer risk profile."
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