A new method to separate and identify malignant cells in breast ductal fluid doubles the sensitivity of detection of cancer compared with standard cytology, according to an article in the June 1 issue of Clinical Cancer Research.

The screen, developed by Sara Sukumar, PhD, and Mary Jo Fackler, PhD, first separates cells from fluid, then sifts through cells’ DNA for hypermethylation of certain genes associated with cancer.

“This screening method can see what the eye cannot see,” said Sukumar, who is the Barbara B. Rubenstein Professor of Oncology at the Johns Hopkins Kimmel Cancer Center. “It can be a valuable tool, in combination with pathological review, for breast cancer as well as other diseases where fluid can be obtained relatively easily, such as lung, head and neck cancers, pancreatic and cervical cancers.”

The new test searches for hypermethylation of cancer-critical regions of DNA. The technique is termed quantitative multiplex methylation-specific PCR or QM-MSP, and it determines the percentage of methylation present in each of five to ten cancer-related genes.

The percentages are added together for a cumulative score, which is compared with a threshold value. Levels above the threshold indicate the potential presence of cancer cells and below threshold suggests that the samples are normal.

In the study, Hopkins researchers compared the cancer-detection rates of the new test versus microscopic review by a pathologist. Breast fluid samples taken from high-risk women or those diagnosed with breast cancer were obtained through ductal lavage, a saline wash via a catheter threaded through openings in the nipple leading to the vast network of breast ducts.

Cytopathologists correctly identified 7 of 21 (33 percent) fluid samples containing cancer, and ruled out the disease in nearly all cases negative for cancer (92 of 93 samples, 99 percent). The new test doubled the cancer detection rate to 71 percent by spotting 15 of 21 samples known positive for cancer. Of 76 samples negative for cancer, the new test concurred on 63 (83 percent).

“Now that we know the screening tool is effective in finding cancer cells within breast duct fluid, we need to improve the accuracy of obtaining the fluid,” said Sukumar, who believes that the gene screen may miss cancers if hidden breast ducts are missed during sampling.

Improvements in getting an accurate representation of fluid from all breast ducts are underway by other investigators and include using sound waves to locate all the ducts.