Molecular Test Accurately Distinguishes Breast Tumors

A new laboratory test has been developed to identify chemical changes to a group of cancer-related genes that can accurately detect which breast tumors are cancerous or benign, and do it in far less time than gold-standard tests on biopsied breast tissue.

In developing countries, women present with late-stage breast lesions due to lack of breast cancer screening/pathology programs. Even after the biopsy of palpable lumps, diagnosis is delayed since most countries in Sub-Saharan Africa average less than one pathologist per million population. Pathology and treatment services are available only at regional hospitals.


A team led by investigators from the Johns Hopkins Kimmel Cancer Center (Baltimore, MD, USA) obtained gathered 226 samples of breast tissue. These samples came from women in the USA, China, and South Africa. Their ages ranged from 25 years old to 85 years old and represented all subtypes of breast cancer: estrogen receptor positive, HER2 positive, triple negative breast cancer, ductal and lobular cancers, and ductal carcinoma in situ (DCIS). Four different kinds of benign lesions and normal breast were also sampled. A genetically diverse collection helped assure that results would be widely applicable. Sampling both malignant and benign lesions allowed the scientists to distinguish methylation differences between the two groups.

The team used these samples, and evaluated the utility of 25 genes that previous studies have shown are often, although not always, methylated differently in breast cancer and benign lesions. A patient’s biopsy sample is loaded into cartridges and inserted in a machine that tests levels of gene methylation, a chemical addition to genes that results in changes in gene activity. Collaborators from Cepheid developed this novel technology platform. This platform returns methylation marker results within five hours. Eventually, they narrowed their 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.

The team evaluated a 10-gene panel using 246 more breast tissue samples, showing similar success in the panel's ability to distinguish cancer from non-cancer. They then ran a pilot study using 73 samples from Portugal and Hong Kong of fine needle aspirates obtained from breast lesions first deemed suspicious through mammography. The test differentiated the 49 benign lesions from the 24 cancerous ones with 96% accuracy. With the five-hour-long return on results, low skill required running the test, and relatively low expense, it could offer hope of speeding diagnosis for thousands of women worldwide.

Saraswati Sukumar, PhD, professor of oncology and pathology and study leader, said, “The hope is that if further studies confirm its value, it could push women who test positive for these 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.” The study was published in the July 2019 issue of the journal Clinical Cancer Research.

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Johns Hopkins Kimmel Cancer Center