Researchers have discovered a method that allows scientists to predict which patients are most likely to suffer serious side effects from chemotherapy. The finding was made in the currently largest study ever on the effects of genetic variability on the toxicity of chemotherapy in breast cancer. The results of the study, which will be presented at the 8th European Breast Cancer Conference (EBCC-8) by Dr. Christof Vulsteke, from the Catholic University of Leuven, in Belgium, shows that the research has achieved a significant step towards achieving personalized chemotherapy regimes for individual patients.

The researchers first analyzed germline DNA from blood samples they obtained from 1,089 breast cancer patients who received three common types of chemotherapy drugs, i.e. fluorouracil, epirubicin and cyclophosphamide between 2000 and 2010, before comparing the side effects experienced in each patient with the variability in the genes that are important for metabolizing these three chemotherapeutic drugs. Germline DNA is the source of DNA for all other cells in the body and comes from the egg and sperm cells that join to form an embryo.

Dr. Vulsteke explains:

“We found that genetic variation in one gene was highly correlated with chemotherapy side effects. Investigating this gene before starting chemotherapy would allow us to support the patient with either growth factors to increase the patient’s immunity, or dose modifications, or a different chemotherapy regimen better adapted to the patient, or a combination of these.”

Although the majority of patients currently receive the standard treatment, the side effects experienced can vary greatly, ranging from very minimal to severe reactions. Adjusting the treatment appropriately would have a major effect on the patients’ physical and psychological wellbeing, as well as on the financial burden to society due to chemotherapy side effects, like for instance, patients requiring hospitalization.

Immune system depression is the main cause of most significant chemotherapy side effects. It can lead to potentially life-threatening infections, and regardless of patient’s attempts to take every precaution necessary to avoid contamination, the vast majority of these infections are caused by microorganisms that occur naturally in the patient’s own gastrointestinal tract. Other serious chemotherapy side effects are nausea, bleeding, vomiting with dehydration, severe infection of the mouth mucosa, and severe bowel inflammation.

Dr. Vulsteke remarks:

“Our research has brought us one step closer towards prescribing personalised chemotherapy treatment with a minimum of side effects.”

To validate their findings, the researchers currently intend to search for data from other European countries, whilst they continue to follow up on their own patients. The average follow-up time for patients is currently five years.

Dr. Vulsteke concludes:

“In 2016 we will have a very accurate assessment of the impact of genetic variation on breast cancer survival and recurrence. Our future research will focus on other genes involved in processing the chemotherapeutic drugs that we studied, and we will also enlarge the scope of the research by including other chemotherapeutic drugs where we can hypothesise that genetic variability plays an equally important role.”

Chair of EBCC-8, Professor David Cameron, from the University of Edinburgh in the UK, commented:

“In the search for ways to “personalize” anti-cancer treatments, much of the focus has been on matching the treatment to the cancer.

However, it should not be forgotten that we also need to ensure the treatment is “matched” to the patient, and this study is an important step in this direction, potentially allowing us to ensure that standard chemotherapy can be delivered with either less severe toxicity, or perhaps to have the dose adjusted to give maximal benefit.

Further studies will be needed to demonstrate that improvements in patient survival can be achieved by tailoring the actual doses along the lines that this study suggests could be possible.”

Written by Petra Rattue