New marker could detect fatal breast cancer up to one year earlier than current methods

December 21, 2017, BioMed Central
breast cancer
Mammograms showing a normal breast (left) and a breast with cancer (right). Credit: Public Domain

A new marker that could be used to diagnose fatal breast cancer up to one year ahead of current methods has been described in a study published in the open access journal Genome Medicine this week. A team of researchers led by University College London, UK found that a region of DNA called EFC#93 showed abnormal patterns of DNA methylation in breast cancer samples. Importantly, these patterns are present in blood serum before the cancer becomes detectable in the breast.

Professor Martin Widschwendter, corresponding author of the study, said: "For the first time, our study provides evidence that serum DNA methylation markers such as EFC#93 provide a highly specific indicator that could diagnose fatal breast cancers up to one year in advance of current diagnosis. This may enable individualized treatment, which could even begin in the absence of radiological evidence in the breast."

Professor Widschwendter added: "We found that the presence of EFC#93 DNA methylation in correctly identified 43% of who went on to be diagnosed with fatal breast cancer within three to six months of giving serum samples, as well as 25% of women who went on to be diagnosed within six to twelve months of giving samples."

DNA methylation is the addition of a group to DNA, which often affects gene expression. Aberrant DNA methylation is common in human tumors and methylation changes occur very early in breast cancer development.

The authors first analyzed EFC#93 DNA methylation in blood serum samples from 419 breast cancer patients taken at two time points: after surgery (before the start of chemotherapy), and after completion of chemotherapy. They demonstrated that aberrant DNA methylation in samples taken before chemotherapy was a marker for poor prognosis independent of the presence of circulating tumor cells (cells that have shed from the primary tumor into the blood or lymphatic system and circulate throughout the body).

To assess whether EFC#93 can diagnose women with a poor prognosis earlier (that is, before the cancer becomes detectable) the authors further analyzed serum samples of 925 healthy women, 229 of whom went on to develop fatal and 231 of whom went on to develop non-fatal breast cancer, within the first three years of donating serum samples.

Professor Widschwendter said: "The serum DNA methylation marker EFC#93 correctly identified 43% of women from serum tested six months in advance of their mammography-based breast cancer diagnosis who later died from the disease (sensitivity for fatal breast cancer) and also identified 88% of women who did not go on to develop (specificity).

"Importantly, EFC#93 did not detect non-fatal breast cancers early. In comparison, mammography screening has a specificity of 88-92% but leads to very substantial over-diagnosis, which means that tumors are detected that would never have caused any clinical symptoms. Subject to further study, using cell-free DNA as a marker, as we have done here, is a promising way of avoiding this issue. "

The authors caution that a lack of appropriate samples is a key limitation of this kind of study. Blood samples that are not processed immediately after blood is drawn, or are not collected in special tubes, contain large amounts of normal 'background' DNA leaked by white cells, which makes it hard to detect small amounts of tumor DNA.

Professor Widschwendter said: "The normal DNA in these samples usually emits a much stronger signal compared with the short fragments of tumor DNA. Yet despite the massive contamination of our population-based samples with normal DNA, we were able to observe a clear DNA signal."

According to the authors, clinical trials are now required to assess whether EFC#93 positive women, who do not have cancer that is detectable by mammography, would benefit from anti-hormonal therapy before the becomes visible in the . Professor Widschwendter's team is currently preparing a large scale population-based cell-free DNA research program which will also help to address this question.

Explore further: Breast cancer prognosis associated with oncometabolite accumulation

More information: Martin Widschwendter et al, Methylation patterns in serum DNA for early identification of disseminated breast cancer, Genome Medicine (2017). DOI: 10.1186/s13073-017-0499-9

Related Stories

Breast cancer prognosis associated with oncometabolite accumulation

December 9, 2013
The metabolic profile of cancer cells can be used to develop therapies and identify biomarkers associated with cancer outcome. In this issue of the Journal of Clinical Investigation Stefan Ambs and colleagues at the National ...

What mediates the beneficial effects of exercise on breast cancer outcomes?

September 8, 2017
The ability of serum obtained from women with breast cancer immediately after finishing two hours of moderate to intense exercise to prevent the growth and survival of breast cancer cells lines in vitro and in mice was attributable, ...

New test predicts the risk of non-hereditary breast cancer

June 27, 2014
A simple blood test is currently in development that could help predict the likelihood of a woman developing breast cancer, even in the absence of a high-risk BRCA1 gene mutation, according to research published in the open ...

DNA methylation level is marker of breast cancer risk

May 11, 2012
(HealthDay) -- Women with high levels of white blood cell (WBC) DNA methylation at the ATM loci have a significantly increased risk of breast cancer, regardless of family history or menopausal status, according a study published ...

Methylation of gene panel may help predict breast CA survival

November 29, 2016
(HealthDay)—Methylation of a gene panel is a strong predictor of survival outcomes in metastatic breast cancer (MBC), according to a study published online Nov. 21 in the Journal of Clinical Oncology.

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Recommended for you

More clues revealed in link between normal breast changes and invasive breast cancer

October 15, 2018
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process—changes in mammary glands to accommodate breastfeeding—uses a molecular process believed ...

Cancer stem cells use 'normal' genes in abnormal ways

October 12, 2018
CDK1 is a "normal" protein—its presence drives cells through the cycle of replication. And MHC Class I molecules are "normal" as well—they present bits of proteins on the surfaces of cells for examination by the immune ...

Obesity linked to increased risk of early-onset colorectal cancer

October 12, 2018
Women who are overweight or obese have up to twice the risk of developing colorectal cancer before age 50 as women who have what is considered a normal body mass index (BMI), according to new research led by Washington University ...

Potential therapy for treatment-resistant hypothyroidism proves effective in lab study

October 12, 2018
A new "metal-coordinated" drug-delivery technology potentially could be used to supplement the standard therapy for hypothyroidism, which affects nearly 10 million Americans, and many more patients worldwide, according to ...

Researchers find a 'critical need' for whole genome sequencing of young cancer patients

October 12, 2018
St. Jude Children's Research Hospital has re-defined the gold standard for diagnostic testing of childhood cancer patients in the precision-medicine era and has implemented the testing for new cancer patients. The findings ...

Immune cells in triple-negative breast cancer offer potential therapeutic target

October 11, 2018
About 15 percent of breast cancers are classified as triple-negative, lacking receptors for estrogen, progesterone, and Her2. These cancers do not respond to targeted hormonal therapies, and they tend to be particularly aggressive, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.