A blood test has been designed that can accurately detect the presence of advanced breast cancer and also may precisely monitor response to cancer treatment. The test, known as 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.
Currently, no useful laboratory test exists to monitor patients with early stage breast cancer who are doing well, but could have an asymptomatic recurrence, said Saraswati Sukumar, PhD, of the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland. 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 examination 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 said 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 breast cancer patients, as well as DNA from the blood of patients with metastatic cancer. 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 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 blood samples from patients with breast cancer and from healthy women without breast cancer. 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 to monitor 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 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.
Their research was published in Cancer Research (2014; doi:10.1158/0008-5472.CAN-13-3392).