In what is said to be a first-of-its-kind study, researchers have found that assessing two types of protein biomarkers increases the accuracy of early cancer detection over the use of either alone. Specifically, the study conducted by Provista Diagnostics Inc., a privately held molecular diagnostics company, shows that combining serum protein biomarkers (SPBs) and tumor-associated autoantibodies (TAAbs) leads to an increase in the sensitivity and specificity beyond that offered by either singly.
The results suggest that the combination of these biomarkers can help healthcare providers decide whether to order additional imaging or biopsy for women who present with abnormal or difficult-to-interpret mammography results.
The study, entitled “Integration of Serum Protein Biomarker and Tumor Associated Autoantibody Expression Data Increases the Ability of a Blood-based Proteomic Assay to Identify Breast Cancer,” was published in PLOS ONE in August, and is part of a broader pipeline of research studies slated for publication in 2016 exploring the use of SPBs and TAAbs in Provista’s blood-based diagnostic test, Videssa Breast.
The researchers examined retrospectively 210 blood samples collected prior to biopsy from women at a single site (Mercy Women’s Center, which was renamed Mercy Breast Center in June 2016) over a six-year period—100 of the participants had been diagnosed with breast cancer (both invasive breast cancer and ductal carcinoma in situ), while 92 were diagnosed with benign breast cancer and 18 showed no evidence of breast cancer. The researchers found that when SPB data were used independently, clinical sensitivity was 74.7 percent and clinical specificity was 77 percent. When TAAb data were independently used, clinical sensitivity and specificity for detection of breast cancer were 72.2 percent and 70.8 percent, respectively.
But when TAAb and SPB data were used together, clinical sensitivity and specificity for detection of breast cancer improved to 81 percent and 78.8 percent, respectively.
The Videssa Breast test was designed to help physicians decide whether to order a biopsy in cases where radiology results are not sufficiently clear. While early detection, chiefly through better mammography screenings and multimodal technologies like magnetic resonance imaging and whole-breast ultrasound, have led to higher cure rates and less morbid treatment, those increasingly sensitive technologies may also be causing an increase in unnecessary biopsies and the discomfort, pain and cost associated with them.
As the authors of the study point out, category 4 on the American College of Radiology’s Breast Imaging–Reporting and Data System (BI-RADS) scale is very broad, including lesions with a 2 percent to 94 percent probability of malignancy. It is, the authors note, a standard practice currently to biopsy all lesions which fall into that category, as well as those in category 5. The majority of the 210 samples collected for this study fell either into BI-RADS category 3 (which is less than a 2 percent chance of malignancy) or BI-RADS 4. For these samples, the researchers found that the negative predictive value of TAAb by itself to be 81.5 percent and of SPB to be 87 percent; combined, the value was 90 percent.
“This study demonstrates clearly that we can offer better diagnostic technologies to not only detect breast cancer at its earliest, most treatable stage but also reduce the rate of benign biopsies, which is important in improving care for women who do not have breast cancer,” said Dr. David E. Reese, president and CEO of Provista Diagnostics.
The authors of the study were careful to note that “[w]hile these data are promising, it should be noted all samples in this study were collected from a single source, which can result in a geographical bias.”
“In a controlled setting,” Reese explains, “a single site study is preferred to make sure patient samples are treated identically and minimize the potential for site-to-site variation. This enables direct assessment of SPB and TAAb contributions to identify breast cancer. Single-site studies are an essential starting point for developing a diagnostic test, allowing for larger, multicenter studies to be planned and powered appropriately.”
Two large, multisite trials have indeed been conducted, allowing researchers to include a more diverse patient population, and results from those trials are expected to be published in late 2016 or early 2017. Reese says that Provista’s Videssa Breast test is currently in limited clinical use through an early access program with initial access to participating clinical trial sites, that a registry trial that will broaden access to patients of participating physicians is in the works for the last quarter of 2016 and that a full commercial launch of the test is anticipated in mid-2017.