MDNews - Long Island

M O R E T H A N 2 . 8 M I L L I O N Americans are breast cancer survivors, according to the American Cancer Society. That means nearly 1 percent of the U.S. population grapples daily with the question of whether their breast cancer is coming back. At present, the standard of care for detecting recurrence in asymp- tomatic patients following successful treatment consists of clinical exams and patient reports. The cMethDNA assay represents a potential fi rst step toward developing a routinely administrable blood test to quash the uncertainty that asymp- tomat ic brea st ca ncer survivors endure. Fi n d i n g s p u b l i s h e d in Cancer Research show that the cMethDNA assay achieves higher sensitiv- ity and specificity than currently used CA 27-29 and circulating tumor cell blood tests. These tests identify the presence of tumor cells in the blood, but the tests detect such markers in only as many as 40 percent of metastatic cancers, according to Sara Sukumar, PhD, Barbara B. Rubenstein Professor of Oncology and Co-Director of the Breast Cancer Program at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. In the team's blinded studies, the cMethDNA assay detected 80–85 percent of metastatic cancer cells in the blood. In terms of specifi city — the ability to identify a particular cancer — CA 27-29 tests achieve a rate of approximately 65 percent and can produce false posi- tives. The cMethDNA assay, on the other hand, is 100 percent specifi c, according to Sukumar. "These are early test results, but it's looking extremely promising that the cMethDNA assay may stand the test of being pitted against other cancer tests and prove to be better than they are in predicting the course of disease and response to treatment," she says. The cMethDNA identifies hyper- methylation — the process by which the disease silences cancer-suppressing genes — in any one of 10 breast cancer- specifi c genes found in tumor DNA. Research included women diagnosed with metastatic cancer, confi rmed by clinical exam and imaging studies, as well as healthy women. "In the fi rst phase of testing, we took women who had metastatic breast cancer and asked whether our test was success- ful in detecting metastasis in metastatic DNA in their serum," says Sukumar, who is also a Professor of Pathology at the Johns Hopkins University School of Medicine. "We showed that in 52 women with recurrent late-stage cancer, we were detecting it with 95 percent accuracy." Monitoring Treatment After initial studies, the research team followed patients throughout chemo- therapy regimens to determine whether the assay could predict responses to treatment. Generally, response to chemotherapy is assessed with a PET/CT scan after eight to 12 weeks. In the meantime, patients are subjected to as many as three months of psychologically and physiologically taxing treatments that may or may not be effective, notes Sukumar. "Our early data analysis tells us that this will probably trump all other tests as far as predicting the course of treatment," she says. "Even at two weeks, you would be able to say the patient will or will not respond to a therapy." The results may prove a game-changing tool in con- structing treatment plans. "We were able to show that within two weeks of giving a particular chemotherapy, the [methylated DNA] levels go down if the patient responds, or the levels creep up if the patient does not respond to the treatment," Sukumar says. "That is a huge help for oncologists to help decide whether they should change the course of treatment. Why continue to give these poisonous drugs to the patient if she's not responding?" Targeting Other Cancers Sukumar and her team also tested the assay's effi cacy on other cancers. Using the same set of 10 genes affected by breast cancer, the team studied the cMethDNA assay on samples from the Cancer Genome Atlas and found potential viability in detecting recurrent colorectal and lung cancers. The team plans to test the concept on the serum in lung or colorectal cancer patients to potentially expand the assay's benefi t to more patients. ■ "We all believe in treating cancer at the earliest detectable time. We always say early detection saves lives. Why should early detection of metastasis not save lives? I believe that catching [recurrence] early and attacking [cancer cells] when their numbers are few is important and will improve the outcomes for breast cancer." — Sara Sukumar, PhD, Professor of Pathology, Barbara B. Rubenstein Professor of Oncology and Co-Director of the Breast Cancer Program at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins SPECIAL CLINICAL SECTION: ONCOLOGY

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