A study looking at why people respond differently to the same chemotherapy (PG SNPS)

These results are in 3 parts.

• 1 part looked at common side effects and treatment outcome (prognosis) 
• Another looked at finding genes that affected side effects
• The 3rd tried to find new genetic variations linked to surviving  breast cancer 

Part 1 - common chemotherapy side effects and treatment outcome (prognosis) 
6, 248 women took part in this study. To begin with, the study team collected information about 13 common side effects the women had while having chemotherapy. Some of these included:

• a drop in the number of white blood cells (neutropenia )
• tiredness (fatigue)
• tingling or numbness in the hands or feet
• feeling or being sick
• constipation or diarrhoea
• a drop in the number of red blood cells (anaemia)
• infection
• muscle and joint pain
• high temperature (fever)

The doctors rated the side effects from mild to severe (from grade 0 to grade 4).

They also did some analysis to work out the likely outcome of someone with breast cancer (their prognosis). This was based on a number of factors including the stage and grade of the cancer and hormone receptors on the cancer cell. 

They then looked to see if there was a link between having any of the side effects and:

• how long the women lived without the cancer coming back - this is called relapse free survival
• the number of women who have survived their breast cancer since their diagnosis or treatment – this is called breast cancer specific survival- it does not include any women who died from any other cause

They found a link with both of these and having a severe (grade 3 or worse) drop in the number of white blood cells (neutropenia). 

So the research team say having severe neutropenia might help predict who is going to survive breast cancer or remain relapse free for longer. They didn’t find a link with any of the other side effects.

Other findings were:

• people who had a low or a healthy body mass index (BMI ) were more likely to have severe neutropenia than people who were overweight or obese
• having moderate to severe fatigue could possibly predict poorer treatment outcomes

The trial team concluded that there is a significant link with having severe neutropenia caused by chemotherapy and improved survival. 

Part 2 - genes that affected side effects
The study team collected 1, 335 blood or saliva samples from women who took part and had a drug called paclitaxel. The DNA  was extracted and stored. 

The study team were looking for small variations (SNPS’s) within genes that might lead to an increased risk of having a side effect that causes tingling or numbness in hands or feet (peripheral neuropathy). 

They looked at 73 possible changes (SNPS’s) in 50 genes to see how they affect peripheral neuropathy risk. 

The study team found there were 2 small changes within these 50 genes that could possibly increase the risk of having numbness or tingling in the hands or feet. 

Part 3 - finding new genetic variations linked to surviving breast cancer
The study team looked at the genetic information of women who took part in this study and some other European studies. They had information for 37, 974 people whose ancestors were from Europe. 

The study team were looking for new genetic variations linked with breast cancer survival.  An overview of these studies (a meta analysis) found 1 possible new genetic area linked with breast cancer survival. It was found in people whose breast cancer cells didn’t have receptors for the hormone oestrogen (oestrogen receptor negative  or ER negative breast cancer). 

This was the largest study looking at genes linked with breast cancer survival. The study team say that finding genetic variations to predict treatment outcome is possible. But there is still a lot of work that needs to be done.