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New Blood Test Detects Recurrent Breast Cancers

Assay finds cancer DNA 95% of the time

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

The test, called the cMethDNA assay, accurately detected the presence of cancer DNA in the blood of patients with metastatic breast cancers up to 95% of the time in laboratory studies.

The findings were reported in the April 15 issue of Cancer Research.

Currently, no lab tests are available for monitoring patients with early-stage breast cancer who are doing well but who could have an asymptomatic recurrence, according to Saraswati Sukumar, PhD, co-director of the breast cancer program at Johns Hopkins. Generally, radiologic scans and standard blood tests are indicated only if a woman reports symptoms, such as bone aches, shortness of breath, pain, or worrisome clinical-examination findings. Otherwise, routine blood tests or scans in asymptomatic patients often produce false positive results, leading to additional unnecessary tests and biopsies. These tests have not been shown to improve survival outcomes in patients with early-stage breast cancer who develop a recurrence.

Sukumar 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 colleagues scanned the genomes of patients with primary breast cancer as well as DNA from the blood of patients with metastatic cancer. The investigators selected 10 genes that are specifically altered in breast cancers, including the newly identified genetic markers AKR1B1, COL6A2, GPX7, HIST1H3C, HOX B4, and RASGRF2, as well as TM6SF1, RASSF1, ARHGEF7, and TMEFF2, which Sukumar’s team had previously linked to primary breast cancer.

The new test detects hypermethylation, 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. They also tested the assay 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% accurate in distinguishing patients with metastatic breast cancer from healthy women.

The investigators also studied the assay’s potential for monitoring a patient’s response to chemotherapy. They evaluated 58 blood samples from 29 patients with metastatic breast cancer, some taken before the initiation of therapy and some taken 18 to 49 days after starting a new chemotherapy regimen. In as little as 2 weeks, the investigators reported, 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 patients 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. They found that the gene panel may also be useful in detecting recurrent lung or colorectal cancers but is not so accurate in detecting recurrent ovarian, kidney, or stomach cancers.

Sukumar is planning additional studies to validate the current findings and to compare the assay’s ability to predict cancer recurrence with that of current imaging tests.

Source: EurekAlert; April 15, 2014.

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