An article from University of Oslo
New insight can lead to better breast cancer treatment
Researchers have now found out what happens when normal cells develop into breast cancer. This finding can lead to more individualized treatment: the right treatment in the right dosage for the right patient.
University of Oslo
Breast cancer can differ from patient to patient, and tumours can vary considerably between patients. We know that the female sex hormone oestrogen plays an important part in the development of the disease. For this reason, breast cancer tumours are divided into two main groups at diagnosis: oestrogen receptor positive tumours (ER-positive) and oestrogen receptor negative tumours (ER-negative).
"This means that we distinguish between tumours with a receptor for the hormone oestrogen and tumours without it. This way of dividing tumours is important in deciding how to treat the cancer," says researcher Thomas Fleischer.
Fleischer and his colleagues at the University of Oslo, Oslo University Hospital and Akershus University Hospital have now found some of the explanation of why tumours are ER-positive or ER-negative.
"We have found epigenetic changes (DNA methylation) that are specific to ER-positive breast tumours. This finding confirms that these are actually two completely different breast cancers that need different treatment," he says.
In Norway, over 3400 people were diagnosed with breast cancer in 2016, according to figures from the Norwegian Cancer Society. Understanding more of how breast cancer develops can lead to more individualized treatment, i.e. the right treatment in the right dosage for the right patient.
"The results of this study mainly provide new insight into the biological mechanisms that cause ER-positive breast cancer. But this insight could also lead to better treatment in the long term," says Fleischer.
Properties of the tumours
ER-positive breast cancers are the largest subgroup of breast cancers, with about 70% of cases, and this division into subgroups determines the treatments available to patients.
"Understanding the basic biology of ER-positive breast cancer is very important in getting to the bottom of how tumours in this subgroup behave, what drives them and what we can do to treat them better," explains Fleischer.
These analyses can also tell us how aggressive the tumours are, in other words, how fast cells are dividing and how quickly the tumour is spreading.
"Even within the subgroups, we see very big differences in how long patients survive. Some may not have needed treatment at all and survived 20 years, while other patients die within 2 or 3 years of diagnosis," he says.
"So there is a huge clinical benefit of a better understanding of ER-positive breast cancer."
In ER-positive tumours, oestrogen will bind to oestrogen receptors.
"That means we can treat these tumours with hormones. Because if the receptors are there, they can be blocked. Fortunately, this treatment works very well for many patients," explains Professor Vessela Kristensen.
The challenge is tumours that do not have the oestrogen receptor on the surface.
"Then we cannot block it because there is nothing to block and the tumour will just keep growing. Here we have to do something else to treat the patient," she says.
DNA methylation: controlling gene expression
DNA methylation is a mechanism that affects and controls how our genes express themselves.
"We have found that abnormally low methylation in ER-positive breast cancer activates cell division and tumours," says Fleischer.
"We have found defects in the control elements that give tumour cells or cancer cells their appearance," she says.
To understand what drives these types of breast cancer, the research team uses advanced models to analyse large amounts of data.
"We perform billions of association tests between DNA methylation and gene expression," says Fleischer.
"This method can also be used for other diseases, and it is therefore a valuable tool for other researchers."
- Thomas Fleischer, Xavier Tekpli et. al. DNA methylation at enhancers identifies distinct breast cancer lineages. Nature Communications, 2017, 8 (1379)