October 10, 2019
4 min read

Molecular test shows potential for faster breast cancer diagnosis

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Saraswati Sukumar, PhD
Saraswati Sukumar

A novel molecular test developed by researchers at Johns Hopkins Kimmel Cancer Center demonstrated the ability to quickly and accurately distinguish between malignant and benign breast tumors.

The test, which identifies chemical changes in cancer-related genes, produces results within 5 hours, potentially hastening diagnosis dramatically for women throughout the world.

“Diagnosis is a huge bottleneck to starting treatment, especially in developing countries that have a small number of pathologists who are available to review breast cancer biopsies and who serve a huge population,” Saraswati Sukumar, PhD, professor of oncology and pathology at Johns Hopkins Kimmel Cancer Center, said in a press release. “That means a test like ours could be especially useful in places with few resources and where mortality rates from breast cancer are much higher compared to the developed world.”

Investigators sought to develop and validate a methylated DNA marker test to differentiate between benign and malignant breast tumors.

According to study results, the methylation marker-based test showed potential in identifying cancerous tissue for expedited pathologic evaluation of breast tumors.

Sukumar told HemOnc Today about the need for the test, the study she and colleagues conducted, and what subsequent research may entail.

Question: What is unique about this test and what need does it serve ?

Answer: Women residing in developing countries often present with late-stage breast lesions due to a lack of breast cancer screening and limited pathology services. Even after the biopsy of palpable lumps, diagnosis is delayed because most countries in sub-Saharan Africa average less than one pathologist per million population. Pathology and treatment services are available only at regional hospitals. This, combined with limited access to effective treatments, leads to high case-fatality rates. For the few and drastically overworked pathologists, there is a need for an accurate, fast and resource-efficient test that can be used in screening clinics to detect malignancies. Such a test would help prioritize patients who need accelerated pathologic and clinical evaluation while reducing the burden on overtaxed health systems.

Q: How did you conduct the study?

A: We developed a novel technology platform in which cells from the palpable mass in the breast, collected with a fine needle, are loaded into cartridges and inserted in a machine that tests levels of gene methylation. This platform returns methylation marker results within 5 hours. To develop the test, we gathered 226 samples of breast tissue from women aged 25 to 85 years across the U.S., China and South Africa. The samples included various subtypes of breast cancer, including ER-positive, HER2-positive, triple-negative, ductal and lobular cancers, as well as ductal carcinoma in situ. Four different kinds of benign lesions and normal breast tissue also were sampled, because a genetically diverse collection would help assure results were widely applicable. Sampling both malignant and benign lesions allowed us to distinguish methylation differences between the two groups. Using these samples, we then evaluated the utility of 25 genes that previous studies have shown are often methylated differently in breast cancer and benign lesions. Eventually, we narrowed the candidate genes to a panel of 10 with methylation characteristics that were more likely able to distinguish between a majority of the malignant and benign training samples. We evaluated this 10-gene panel using 246 more breast tissue samples, showing similar success. We then ran a pilot study using 73 samples of fine needle aspirates obtained from breast lesions of patients in Portugal and Hong Kong that were first deemed suspicious through mammography.


Q: What did you find?

A: We found that the test holds promise as a ‘first pass’ to distinguish between malignant and benign breast tumors. With the 5-hour-long return on results, low skill required to run the test and relatively low expense, it could offer hope of speeding diagnoses for thousands of women worldwide. However, the test does not replace expert analysis by a pathologist whose skills are necessary to review core biopsies for a definitive diagnosis and optimal therapy recommendations.

Q: What is next for research on this?

A: We plan to perform clinical studies to see if we can get this to work in the real-world setting. Our team recently visited Chris Hani Baragwanath Academic Hospital, the largest hospital in South Africa, with huge annual volumes of benign and malignant breast disease. The need for such a fast test was obvious, because delayed diagnosis was common in the outlying hospitals in the distant suburbs. The oncologists and pathologists were so impressed with the potential of the cartridge test to hasten detection that they are poised to initiate a pilot study immediately. A similar study is being conducted and led by Gerard Mullen, MD, gastroenterologist at The Johns Hopkins Hospital, where 50 women have been entered thus far. The lab personnel will examine smears of cells from suspicious breast lesions and determine if the test provides reproducible results, and with what accuracy. We are seeking funding to start this study in South Africa as soon as possible.

Q: Is there anything else that you would like to mention?

A: We hope that further studies will confirm the value of the test, which could push women who test positive for methylation markers to the front of the line to have their biopsies reviewed rapidly by the few pathologists in developing countries. Instead of languishing for months while they wait for a diagnosis, patients can start potentially lifesaving treatments right away. – by Jennifer Southall


Downs BM, et al. Clin Cancer Res. 2019; doi:10.1158/1078-0432.CCR-18-3277.

For more information:

Saraswati Sukumar, PhD, can be reached at Johns Hopkins Kimmel Cancer Center, 1650 Orleans St., CRB 1 Room 144, Baltimore, MD 21287; email: saras@jhmi.edu.

Disclosure: Sukumar reports a paid consultant role with Cepheid.