Tailored treatments
for breast cancer

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TRANSBIG
Breast cancer patients could soon benefit from highly individualised treatment, thanks to the diagnostic tools being developed by the TRANSBIG project. Among other things, TRANSBIG is running a major clinical trial to test the effectiveness of a tool to identify which women need chemotherapy after surgery (called adjuvant chemotherapy), and which do not.

If it works, the tool will spare many women from undergoing adjuvant chemotherapy unnecessarily, saving them from unpleasant side effects and also saving health systems the costs of treating patients with drugs they do not need.

TRANSBIG, which is coordinated by the Breast International Group (BIG), brings together 40 partners from 21 countries. They include universities, research institutes and hospitals with expertise in biomedical technologies and cancer treatment, patient organisations, cancer societies and small biomedical companies. Its overall aim is to translate the results of experiments in laboratories into tools that doctors can use to treat breast cancer patients more effectively.

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Breast cancer basics

Breast cancer is the most common cancer among women in developed countries, where one woman in eight develops the disease at some point in her life. According to the International Agency for Research on Cancer, 320 000 women were diagnosed with breast cancer in the EU in 2006, and 85 000 died of the disease.

If diagnosed and treated promptly, breast cancer is curable in roughly two thirds of cases. Many women are given chemotherapy or hormone treatments after surgery to prevent the cancer from recurring. These treatments bring with them a range of unpleasant side effects, which may include secondary cancers, heart problems, early menopause and reduced cognitive function.

While some women need these cancer treatments, others do not. It is thought that between 12 % and 20 % of early breast cancer patients are over-treated. The TRANSBIG consortium is drawing on the outcomes of basic research to develop tools which can help doctors answer two key questions: which patients need treatment, and what is the best treatment for each patient?

The way breast cancer develops varies from one woman to another. Traditionally, the aggressiveness of the tumour is determined on the basis of clinical and pathological criteria such as the patient’s age, the tumour’s size, the appearance of the tumour cells (their ‘grade’) under the microscope and the presence of hormone and HER-2 (human epidermal growth factor receptor 2) receptors on the tumour cells.

Advances in fields such as genomics mean that we now have a better understanding of the biological differences between tumours.

One of the main messages is that breast cancer is a very heterogeneous disease with several different subtypes that behave quite differently. This is why we need more individualised approaches to treating breast cancer.

Testing new technologies to tailor treatments

The project’s first major initiative is an international clinical trial called MINDACT (MIcroarray for Node Negative Disease may Avoid ChemoTherapy). Node-negative breast cancer is a cancer that has not spread to the surrounding lymph nodes and so has a lower risk of recurrence. Patients with this variety of cancer are often given chemotherapy, even though 15 % of them do not need it.

The aim of MINDACT is to compare the traditional method of assessing a tumour’s aggressiveness with a new method called the 70-gene prognostic signature (Mammaprint ®). As the name suggests, the new method analyses the activity levels of 70 genes inside the tumour. Previous research suggests that the ‘signature’ pattern of these genes can accurately predict whether or not a woman’s breast cancer will return.

In the trial, a tissue sample from the patient is sent to the laboratory where it is subjected to both traditional tests and the new test. If both methods indicate a low risk of recurrence, chemotherapy is not recommended. If both methods suggest a high risk of recurrence, the patient is advised to have chemotherapy.

However, in cases where the tests disagree, some patients are treated on the basis of the result of the traditional test, and some are treated on the basis of the result of the new test. Needless to say, all patients involved in the trial are closely monitored by doctors throughout the process. The trial includes some 6 000 women from 250 institutions around the world.

The project partners predict that using the 70-gene test in combination with the traditional clinical pathological analysis will provide a more accurate picture of the risk of recurrence for the patients. And some 10 % to 20 % of women with node-negative breast cancer will be able to avoid chemotherapy and the side effects that come with it.

Recently, the 70-gene test was validated as a tool in breast cancer involving one to three lymph nodes. Consequently, those patients will be able to enter the trial very soon. MINDACT’s new name (Microarray for Node Negative and 1 to 3 Positive Nodes Disease may Avoid ChemoTherapy) reflects this development.

Leaving a lasting legacy

In addition to carrying out research, the project partners are also engaged in education and outreach activities. They provide traineeships for young scientists and physicians and work closely with patient groups to inform them of the latest developments in genomics research.

In the long term, the project partners hope to turn TRANSBIG into a permanent network for translational breast cancer research that will act as a bridge between the researchers working in laboratories and the physicians and patients in the clinic.

However, the project’s real legacy will be the improved quality of life experienced by the many women who will be spared unnecessary adjuvant chemotherapy thanks to TRANSBIG’s work.