Blood test spots recurrent breast cancers, monitors response to treatment

April 15, 2014, Johns Hopkins University School of Medicine

Johns Hopkins Kimmel Cancer Center investigators report they have designed a blood test that accurately detects the presence of advanced breast cancer and also holds promise for precisely monitoring response to cancer treatment.

The , called the cMethDNA assay, accurately detected the presence of cancer DNA in the of patients with metastatic breast cancers up to 95 percent of the time in laboratory studies. The findings were described in the April 15 issue of the journal .

Currently, there is no useful laboratory test to monitor patients with early stage breast cancer who are doing well, but could have an asymptomatic recurrence, says Saraswati Sukumar, Ph.D., who is the Barbara B. Rubenstein Professor of Oncology and co-director of the Breast Cancer Program at the Johns Hopkins Kimmel Cancer Center. Generally, radiologic scans and standard blood tests are indicated only if a woman complains of symptoms, such as bone aches, shortness of breath, pain, or worrisome clinical exam findings. Otherwise, routine blood tests or scans in asymptomatic patients often produce false positives, leading to additional unnecessary tests and biopsies, and have not been shown to improve survival outcomes in patients with early stage breast cancer who develop a recurrence.

Sukumar, also a professor of pathology at Johns Hopkins, says that the current approach to monitoring for recurrence is not ideal, and that "the goal is to develop a test that could be administered routinely to alert the physician and patient as soon as possible of a return of the original cancer in a distant spot. With the development of cMethDNA, we've taken a first big step toward achieving this goal."

To design the test, Sukumar and her team scanned the genomes of primary , as well as DNA from the blood of metastatic cancer patients. They selected 10 genes specifically altered in breast cancers, including newly identified genetic markers AKR1B1, COL6A2, GPX7, HIST1H3C, HOX B4, RASGRF2, as well as TM6SF1, RASSF1, ARHGEF7, and TMEFF2, which Sukumar's team had previously linked to primary breast cancer.

The test, developed by Sukumar, collaborator Mary Jo Fackler, Ph.D., and other scientists, detects so-called hypermethyation, a type of chemical tag in one or more of the breast cancer-specific genes present in tumor DNA and detectable in cancer patients' blood samples. Hypermethylation often silences genes that keep runaway cell growth in check, and its appearance in the DNA of breast cancer-related genes shed into the blood indicates that cancer has returned or spread.

In one set of experiments, the researchers tested the assay's ability to detect methylated tumor DNA in 52 blood samples – 24 from patients with recurrent stage IV breast cancer and 28 from healthy women without breast cancer, and again in blood samples from 60 individuals – 33 from women with all stages of breast cancer and 27 from healthy women. In each case, the blood test was up to 95 percent accurate in distinguishing patients with from healthy women.

The investigators also studied the assay's potential to monitor response to chemotherapy. They evaluated 58 from 29 patients with metastatic , some taken before the initiation of therapy and some taken 18 to 49 days after starting a new chemotherapy regimen. In as little as two weeks, they report, the test detected a significant decrease in DNA methylation in patients with stable disease or in those who responded to treatment; this decrease was not found in whose disease progressed or who did not respond to treatment.

"Our assay shows great potential for development as a clinical laboratory test for monitoring therapy and disease progression and recurrence," Sukumar says. If it's determined early that a treatment is not working, clinicians can save time and switch to a different therapy, she says.

In addition, the researchers tested the gene panel used in the cMethDNA assay against samples from The Cancer Genome Atlas, a catalog of genes in various cancer types, finding that the gene panel may also be useful in detecting recurrent lung or colorectal cancers but not as accurate in detecting recurrent ovarian, kidney or stomach cancers.

There is a patent pending on the test, says Sukumar, who is planning additional studies to validate the current findings and compare its ability to predict recurrence with that of current imaging tests.

Explore further: DNA shed by tumors shows promise for non-invasive screening and prognosis

Related Stories

DNA shed by tumors shows promise for non-invasive screening and prognosis

March 6, 2014
(Medical Xpress)—Certain fragments of DNA shed by tumors into the bloodstream can potentially be used to non-invasively screen for early-stage cancers, monitor responses to treatment and help explain why some cancers are ...

A simple blood test could be used to detect breast cancer

October 1, 2012
A simple blood test could one day be a more accurate way to test for the early signs of breast cancer than using mammograms to spot a lump say researchers today, as Breast Cancer Awareness Month gets underway.

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 ...

Scientists pair blood test and gene sequencing to detect cancer

November 28, 2012
Scientists at the Johns Hopkins Kimmel Cancer Center have combined the ability to detect cancer DNA in the blood with genome sequencing technology in a test that could be used to screen for cancers, monitor cancer patients ...

New prognostic test for breast cancer could improve patient treatment

March 11, 2014
A study by researchers in Nottingham has developed a new clinical test for breast cancer which aims to improve patient treatment.

Faster genetic testing method will likely transform care for patients with breast cancer

March 27, 2014
Faster and cheaper DNA sequencing techniques will likely improve care for patients with breast cancer but also create challenges for clinicians as they counsel patients on their treatment options. Those are among the conclusions ...

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

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.