By Deborah Borfitz
January 13, 2022 | Mammography has a lot of well-recognized shortcomings among women with dense breasts as well as those diagnosed with breast cancer who need their response to therapy closely monitored. A cheaper, noninvasive, and easy-to-perform test is now under development that could solve for its clinical limitations and is on track to hit the market as early as 2023, according to Benjamin Sanchez-Terrones, electrical and computer engineering assistant professor at the University of Utah and member of the Experimental Therapeutics program at the Huntsman Cancer Institute.
Using electricity to evaluate the health of breast tissue, the cart-sized device exploits the body’s immune response to predict whether a woman has cancer. It’s a completely safe and painless tool that measures skin electrical resistance, based on the principle that cancer causes lymphatic interstitial fluid to be less electrically conductive, Sanchez-Terrones explains.
The technique is not unlike others electrodiagnostic tests, such as needle electromyography (EMG), already routinely used in clinical practice for neuromuscular evaluation, he continues. Both use electricity. While patients hold one electrode, the operator touches different parts of their body with a handheld probe containing a second electrode, closing the electrical circuit and allowing a painless electrical current flow through the body.
In pilot testing, measurements of patients’ skin electrical resistance were taken at up to 40 specific anatomical locations over the course of 30 minutes, says Sanchez-Terrones. A machine learning algorithm in the device then analyzed the data points to calculate the likelihood that they did or did not have cancer.
The anatomical reference points will be standardized as the device moves closer to clinical use, he adds, when the landmarks measured could be far fewer in number. Test results will also be integrated into the device, versus calculated offline as is being done currently.
As reported recently in IEEE Access (DOI: 10.1109/ACCESS.2021.3123569), the proof-of-concept study demonstrated that skin electrical resistance changes could serve as a diagnostic and therapeutic biomarker associated with malignant versus benign breast cancer lesions. Among 48 study participants, 24 with malignant breast cancer and 23 with benign lesions, the procedure had a positive predictive value of 70% and negative predictive value of 75%.
The two-electrode DC system is a product of IONIQ Sciences (Salt Lake City), where Sanchez-Terrones serves as a scientific advisory board member. His role in the pilot study was to help the company analyze the data to identify differences between benign and malignant breast cancer lesions.
A reimbursement code for the technology won’t be generated until the device is approved by the U.S. Food and Drug Administration (FDA). But cost of the test will in any case be “significantly cheaper” than a mammogram, making it financially feasible to repeat with some regularity.
IONIQ Science’s first product utilizing its proprietary analytic platform, the IONIQ ProLung Test for lung cancer, has been designated a Breakthrough Device by the FDA and has no predicate. As stated on its website, the company aims to be the first FDA-cleared multi-cancer screen and the lung and breast cancer tests are foundational to that quest.
Clinical Utility
While not as accurate as mammography, which can be 80% to 98% effective in detecting breast cancer in older women with non-dense breast tissue, skin bioimpedance testing has potential diagnostic utility for younger women and women with dense breast tissue who are otherwise advised not to get a mammogram, Sanchez-Terrones says. The idea is for bioimpedance to be used as an adjunctive test to mammography—much like ultrasonography—to potentially improve screening rates among young women and help to improve the confidence of radiologists when mammograms are inconclusive.
A negative mammogram result for women with dense breasts might be followed by confirmatory skin electrical resistance testing, he offers as an example. A positive result on that secondary test would give physicians “sufficient ammunition” to order an MRI and have third-party payers help cover the cost.
The device would most importantly serve as a convenient screening tool for breast cancer and evaluation of therapy, he adds. Unlike mammography, “the technology we have doesn’t care if you have dense breast tissue or you don’t.” And because no radiation is involved, the skin electrical resistance test can be repeatedly as often as necessary.
The test could logically become part of the annual checkup women have with their primary care physician, although it isn’t even necessary for the operators to be doctors. With minimal training, a nurse could take the measurements, notes Sanchez-Terrones.
Conceivably, bioimpedance testing could be done at home as a convenience for people living many miles from a properly equipped hospital or physician’s office, he adds. But the machine would likely be cumbersome in those more space-limited environments.
For women undergoing breast cancer treatment, the device might also be used to monitor therapeutic response more frequently than what is possible with mammography due to the risk associated with radiation exposure, he continues. In the pilot study, six women diagnosed with malignant breast cancer had skin electrical resistance measurements taken before starting treatment and again six months later when the values fell to levels consistent with benign breast lesions.
In clinical practice, the noninvasive measurements might be taken much more frequently than currently possible, perhaps weekly, Sanchez-Terrones says. Doctors might thereby be able to adjust their treatment strategy sooner if patients aren’t responding well. For pharmaceutical companies, the technology also opens a new door to evaluate the effectiveness of new drugs safely and quickly.
Long History
Sanchez-Terrones is no stranger to clinical applications of electrical impedance and even co-founded a company, Haystack Diagnostics, which has licensed one of his inventions for its needle EMG technology used to evaluate electrical activity of the muscle. EMG involves inserting one or more tiny needles into muscles to detect abnormalities in their electrical activity.
Up until mid-2020, Sanchez-Terrones worked in the department of neurology at Harvard Medical School’s Beth Israel Deaconess Medical Center in Boston. At his lab at the University of Utah, he has expanded the landscape of bioimpedance for health-related applications and is now investigating electrical bioimpedance approaches to detecting skin as well as breast cancers.
The skin cancer work is being done in collaboration with dermatologist Douglas Grossman, M.D., Ph.D., co-leader of the melanoma center at Huntsman Cancer Institute. A new screening device developed in Sanchez-Terrones’ lab termed URSKIN proved effective in differentiating normal from skin cancerous tissue in a pilot study enrolling 17 of Grossman’s patients, as just reported in JID Innovations (DOI: 10.1016/j.xjidi.2021.100075).
Pioneers of biomedical engineering started using electricity for tissue evaluation about 100 years ago, notes Sanchez-Terrones. Initially, it was being applied to understand the basic science governing the propagation of electricity through tissues but evolved into a clinically driven field where researchers sought to decipher the meaning of the signals generated, how to measure them, and how they’re related to etiology. The quest now is to capture those signals noninvasively from tissue.
Still to be established with the IONIQ device is how early breast cancer can be detected via bioimpedance and if this is dependent on the number of measurements taken on the body’s systemic immune response, Sanchez-Terrones says. But results of the pilot study are promising, with cancer being detected in patients with stage 1 to stage 4 disease, he adds.