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Automated Breast Cancer Detection Assay Using Fine-Needle Aspiration May Aid Patients in Developing Countries

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Key Points

  • The researchers evaluated this 10-gene panel, showing similar success in the panel’s ability to distinguish cancer from noncancerous samples.
  • They then ran a pilot study using 73 samples obtained from breast lesions first deemed suspicious through mammography. The test differentiated the 49 benign lesions from the 24 cancerous ones with 96% accuracy.

A new laboratory test developed to identify chemical changes to a group of cancer-related genes may be able to accurately detect which breast tumors are cancerous or benign. Such a test could result in a more timely diagnosis of breast cancer for women in developing countries with less access to screening and pathology programs. A report on the effectiveness of this assay was published by Downs et al in Clinical Cancer Research.

Although the findings are preliminary and need further validation in larger groups of people, the investigators say the test has the potential to reduce the time (minimum by 1 month, maximum by 15 months) generally needed to make a definitive breast cancer diagnosis in poorer countries. A quick diagnosis has already been definitively proven to boost survival for all cancers by reducing wait times to surgical and other treatments.

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

Breast Cancer Diagnosis in Developing Countries

Dr. Sukumar also noted that breast cancer incidence is rising around the world. In 1980, GLOBOCAN reported 641,000 new cases of breast cancer worldwide. In 2018, the estimated incidence of breast cancer worldwide rose to 2.1 million cases (a 3.2% annual rate of increase) with 626,000 deaths due to breast cancer reported.

In developing countries, women often present with late-stage disease due to lack of breast cancer screening/pathology programs. This, combined with limited access to effective treatments, leads to high case-fatality rates. An accurate, fast, and resource-efficient test for use in screening clinics that can detect malignancies would greatly assist in prioritizing patients who need accelerated pathologic and clinical evaluation, while reducing the burden on overtaxed health systems, Dr. Sukumar explained.

Development of the Assay

Seeking to shrink the time from biopsy to diagnosis, researchers developed a novel technology platform where 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. This platform returns methylation marker results within 5 hours.

To develop the test, the researchers gathered 226 samples of breast tissue. These samples came from women in the United States, China, and South Africa. Their ages ranged from 25 years old to 85 years old and the sample represented all subtypes of breast cancer: estrogen receptor–positive, HER2-positive, triple-negative breast cancer, ductal and lobular cancers, and ductal carcinoma in situ. 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 researchers to distinguish methylation differences between the two groups.

Results

Using these samples, the team evaluated the utility of 25 genes that previous studies have shown are often—although not always—methylated differently in breast cancer and benign lesions. 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 researchers evaluated this 10-gene panel using 246 more breast tissue samples, showing similar success in the panel’s ability to distinguish cancer from noncancerous samples. 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.

These results suggest that the test holds promise as a “first pass” to distinguish between malignant and benign breast tumors, said Dr. Sukumar. With the 5-hour return on results, low skill required to run the test, and relatively low expense, it could offer hope of speeding diagnosis for thousands of women worldwide.

Dr. Sukumar cautioned that the molecular test cannot replace expert analysis by a pathologist, whose skill will be necessary to review core biopsies of the breast lesion for a definitive diagnosis and optimal therapy recommendations. 

“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,” explained Dr. Sukumar.

Disclosure: This work was supported by Under Armor, AVON Foundation for Research, Cepheid, and the CCSG Core Grant. For full disclosures of the study authors, visit clincancerres.aacrjournals.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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