The identification of five genes involve in the metastasis of breast tumours to the lung is the principal finding of a scientific team made up of two bodies from the University of Navarra, the Applied Medical Research Centre (CIMA) and the University Hospital of the University of Navarra.

Doctor Alfonso Calvo, researcher in the area of Oncology at the CIMA, led the work with the special collaboration of Doctor Ignacio Gil Bazo, cancer specialist from the University Hospital.  The study made up a significant part of Mr Raúl Catena’s PhD thesis.

For this research, recently published in the scientific journal Oncogene, a transgenic mouse model which presented a greater tendency for developing metastasis was employed.  The increase in what is known as the Vascular Endothelial Growth Factor (VEGF) in its mammary glands triggered profound changes in the tumoural structure, which enabled the malignant cells to leave the tumour and invade the lungs.

Finally, the pattern of genes responsible for this tumoural migration to the lungs was analysed and this was compared to that shown by women with breast tumours with pulmonary metastatic affectation.  It was shown that five of these genes were common to the animal model and patients with breast cancer.  Most effective ways of treatment

According to the results of this study, of the five genes identified, the Tenascina-C gene seems to be a good therapeutic target for the treatment of metastatic breast cancer.  In fact, the blocking of the expression of this gene in the animal model enabled a significant reduction, both in tumour growth and in the incidence of pulmonary metastasis.

This new discovery in the complex network that is the metastasis process of tumours provides key data on the knowledge of cancer and its spreading, at the same time identifying new targets for which new pharmaceutical medicines that contribute to more efficacious treatment of this disease can be designed.

Breast cancers behave differently before and after the age of 70 Do the immune defense mechanisms play a role?

Berlin, Germany: Researchers in Belgium have discovered that increasing age affects the way breast cancer behaves.  As women approach the age of 70, they become less likely to be diagnosed with aggressive tumours that have spread to the lymph nodes.  But after 70, the cancer is increasingly likely to spread, particularly if the tumours are small.

Until now, there has been conflicting evidence on aging and lymph node involvement and this study is the first to show clearly how the link between the two changes before and after the age of 70.

Professor Hans Wildiers told the 6th European Breast Cancer Conference (EBCC-6) in Berlin today (Friday), that he suspects that women older than 70 have decreased immune defence mechanisms, which are less able to deal with tumours that are likely to metastasise to other sites in the body.

“The effect of age of lymph node positivity is not straightforward.  There seems to be a different effect between women aged up to 70 years and women older than 70.  For the younger group of women, age appears to have a negative effect on lymph node status – the older they become, the less likely the cancer is to have spread to the lymph nodes.  For the older group of women (aged over 70), age appears to influence lymph node status in the opposite way – the older they become, the more likely they are to have cancer cells in the lymph nodes if the tumour is small,” said Prof Wildiers, who is adjunct head of clinic in the department of general medical oncology at the Multidisciplinary Breast Centre, University Hospitals Leuven, Belgium.

“There is an interaction between age and tumour size, suggesting that, up to the age of 70, age mainly has a positive effect on lymph node status for older women with small tumours.  A likely explanation is that breast tumours metastasise less frequently to lymph nodes with increasing age due to the decreased biological aggressiveness in these tumours.  On the other hand, over the age of 70, if the tumours have the potential to metastasise to lymph nodes, this occurs more rapidly in smaller tumours and this might be related to decreased immune defence mechanisms in elderly patients.”

Prof Wildiers and his colleagues investigated 2,227 women who had been treated for breast cancer between 2000 and 2006 at the University Hospitals Leuven.  Then they compared the results with a separate database of over 11,000 breast cancer patients on the Eindhoven Cancer Registry.

They found that for women aged 70 or younger, increasing age was associated with a decreased prevalence of cancer spreading to the lymph nodes.  The women’s risk of having positive lymph nodes decreased by 13% for every decade they aged, up to age 70.

Once aged 70 and over, the odds of lymph node involvement doubled with every 10-year increase in age for women who had tumours that were no bigger than 15mm across.  If the tumours were larger than 42-43 mm, then risk of lymph node involvement continued to decrease.

Prof Wildiers said: “We know that the elderly have depressed immune defences, and, therefore, it is possible that these decreased defences are unable to prevent invasion of the lymph nodes by metastases in a subset of breast tumours in elderly women.  Although breast cancer survival in older women appears to be similar to survival in the general population irrespective of disease status, it might well be that there is a balance in the elderly between, on the one hand, a less aggressive type of tumour, and, on the other hand, their decreased immunological defences.”

He said the findings supported the idea that there are two types of tumour in elderly women: ones that are slow-growing and don’t invade the lymph nodes even if the tumours are larger, and ones that are aggressive and metastasise very early to the lymph nodes.  Women with slow-growing tumours might benefit from less aggressive treatment, while the smaller tumours in the women aged over 70 might need to be treated more aggressively.

“Further research now needs to be conducted into the role the immune system plays in lymph node invasion,” he concluded.

Reference:
Catalogue no: 401, Friday, Poster discussion session, 14.30 hrs CEST (Hall 2)