A new test has been developed which can predict whether a breast cancer patient will respond to chemotherapy within 24-hours of starting treatment, thus sparing her unnecessary treatment and side effects, according to a study published in the medical journal Clinical Cancer Research. The test can also determine whether the woman can benefit from PARP-inhibitors, a promising new type of cancer treatment currently undergoing clinical trials.

The test was developed at the Breakthrough Breast Cancer Research Centre, at The Institute of Cancer Research (ICR), London, England. Researchers say the test will be able to determine which patients will likely benefit from anthracycline chemotherapy – a standard treatment for a significant number of the 46,000 people diagnosed with breast cancer in the UK annually.

The researchers examined RAD 51, one of the key proteins involved in DNA repair. The study, involving 68 patients, all of them with breast cancer, found that in some cases RAD51 did not work in cancer cells. They report that anthracycline is much more likely to have a beneficial effect in cases where RAD51 did not work on cancer cells.

A significant percentage of patients responded well, with their tumor completely disappearing from the breast. If the DNA repair process was working in the tumour, they would probably not respond to the treatment, with complete response being unlikely.

Dr Nicholas Turner, team leader, the Breakthrough Breast Cancer Research Centre at the ICR, said:

This test may reduce the time taken to discover if a breast cancer patient is not going to have a good response to a chemotherapy from three months to just 24 hours. It would make a big difference to patients, who could be moved onto other treatment options sooner ” and spared unnecessary side effects.

This test is at an early stage of development and now needs to be confirmed in larger studies to see if it can be effective.”

Patients who are likely to respond to PARP inhibitors could also be identified, Turner added. According to recent research, up to 30% of patients could be treated effectively with PARP inhibitors. PARP inhibitors are not yet licensed for use; they are still in clinical trials. This test could help speed up the development of PARP inhibitors and similar cancer medications.

Professor Alan Ashworth, Director of the Breakthrough Breast Cancer Research Centre at the ICR, said:

We want to see all breast cancer patients get the right treatment at the earliest possible stage. This test is a step towards that aim and we now want to develop it so that it can be used routinely in the clinic. It is also exciting because it suggests a way of finding patients that might respond to PARP inhibitors.

Finding out in 24 hours, rather than the current 12 weeks to determine whether a woman has responded to chemotherapy, which typically is a combination of two or three drugs, will spare patients who will not respond nearly three months of wasted time and needless side effects, the researchers say. In a presentation yesterday, Dr. Turner said:

We’ve developed a test that can work out within 24 hours after the first lot of chemotherapy, whether the patient is likely to do well or not on the chemotherapy.

We think that the main benefit from this type of research is to identify patients who are going to respond or not to chemo much earlier. The patients who are not going to respond, potentially they could then be switched to different kinds of chemotherapies or hormone therapy. The very significant advantage of that is we can then spare unnecessary treatment and unnecessary side effects.

We have looked at a protein called RAD51 in the biopsies taken from the breast cancer, only 23 hours after the first chemo. RAD51 is one of the key proteins involved in DNA repair, and by looking at RAD51 we’ve been able to work out whether the cancer is sensitive to chemotherapy or not, very early and much earlier than we would do normally.

By using this test, we potentially are also able to predict whether patients are able to respond to a very exciting new class of cancer drugs called PARP inhibitors. PARP inhibitors are only involved in clinical trials at the moment, but there is a lot of excitement that they may be particularly good drugs for certain types of breast cancer..This new test on RAD 51 may also predict which patients are likely to benefit from PARP inhibitors.

“A marker of homologous recombination predicts pathological complete response to neoadjuvant chemotherapy in primary breast cancer”
Monika Karla Graeser, Afshan McCarthy, Christopher J Lor, Kay Savage, Margaret Hills, Janine Salter, Nick Orr, Marina Parton, Ian E Smith, Jorge Reis-Filho, Mitchell Dowsett, Alan Ashworth, and Nicholas Turner
Clinical Cancer Research Published OnlineFirst August 27, 2010; doi: 10.1158/1078-0432.CCR-10-1027

Written by Christian Nordqvist