Breast
New molecular marker of resistance to chemotherapy in breast cancer
By IDIBAPS - Institut d'Investigacions Biom�diques August Pi i Sunyer
Jul 10, 2006 - 8:14:00 PM

A collaborative study between the Hospital Cl�nic and the Hospital del Mar de Barcelona permits to establish a predictive factor in the resistance to chemotherapy in breast cancer and to establish possible therapeutic targets for the improvement of this treatment.

This study shows clinical evidence of the role played by the nuclear factor (NF)-kappaB in breast cancer and makes it a key target for new treatments, both to be aware of its existence and to predict a low chemotherapy response. If this is the case, the blocking of the factor prior to treatment is needed in order to increase the efficiency of treatment. The results of this study are the first to be published in which nuclear factor (NF)-kappaB, which promotes the survival of cells, has been specifically studied in order to observe its relevance in the prediction of response to chemotherapy.

Breast cancer is the most frequent cancer among women around the globe, with more than one million cases every year. It is the first cause of lost of potential years of life, and the second leading cause of cancer death among women. Breast cancer is one of the diseases causing more disorders to women in the developed countries because of the increase of new cases, its high mortality and the social repercussion it entails.

In Catalonia, the prevalence of breast cancer is of more than 50,000 women. Although the number of cases and incidence rate increase every year, mortality rate decreases. Survival of patients is improving, achieving a 5 year survival of almost 80%, a number higher than the European mean. The improvement of the screening programmes and the continuous improvements in treatment underlie the key of success in the decrease of mortality. Chemotherapy treatment plays an important role in recovery or increase of survival of these patients. Now, a new line to improve results consists in finding which patients are benefited from chemotherapy in order to make a personalized treatment.

This study has contributed to the understanding of one of the resistance mechanisms to chemotherapy previous to surgery in patients of locally advanced breast cancer. If the response to preoperational chemotherapy is improved, not only survival improves, but also surgeries can be less radical, preservation of the breast is possible and decrease the psychological, emotional and social impact of the treatment is achieved.

"Results show that patients with breast cancer who presented activated nuclear factor (NF)-kappaB in tumour cells prior to treatment with chemotherapy, only achieve 20% response to chemotherapy", explains Dr. Tusquets, "whereas if (NF)-ĸB is not activated, chemotherapy response increases up to 91%". Moreover, the relevance of this factor has been confirmed since the activation of (NF)-kappaB increases after chemotherapy exposure, what could explain part of the acquired chemotherapy resistance during treatment.

The repercussion of this study and the fact that it confirms clinically other cellular results permits to consider this study as a departure point for future studies regarding this factor in collaboration with other hospitals, and to be able to offer personalized treatments in the future. "Not only can we predict chemotherapy response of tumour before treatment is started, but also can we search for a mechanism to act upon the nuclear factor (NF)-kappaB, deactivate it and permit an efficient chemoterapy" concludes Dr. Montagut, the first signatory of this article.

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