Diagnostics & Imaging Week

AviaraDx (Carlsbad, California) believes it may be able to help 30% of women who are diagnosed with breast cancer and are estrogen receptor-positive (ER+) and lymph node-negative — the best possible diagnosis in the disease. Yet about 10% to 15% of those women go on to develop a cancer recurrence, despite the good prognosis.

Through its discovery of two biomarkers, HOXB13/ ILI7BR (HI), which can be determined as a ratio in women with the above diagnosis, AviaraDx says that this two-gene ratio is extremely important. "The H over I, is a highly significant prognostic factor in ER-positive, node-negative women," Chief Scientific Officer Mark Erlander, PhD, told Diagnostics & Imaging Week.

"HOXB13 is really the bad actor here," Erlander said. "Within ER+ patients, only 30% to 40% of those express HOXB13, and if it's expressed, that's a bad thing. The majority of women – 60% to 70% — don't express HOX, and so they have a good prognosis. But [our biomarkers are] really about identifying those 30% of women, and that's really what this two-gene ratio is all about."

Breast cancer is diagnosed in more than 200,000 women and claims the lives of more than 40,000 each year in the U.S., AviaraDx said. About 70% of breast cancers are ER+, and most of these are early stage, or lymph node-negative.

Last week, the company reported that an 852-patient retrospective study confirms the original discovery of the H/I ratio as an independent prognostic marker for risk of recurrence in tamoxifen-treated, ER+ and lymph node negative patients.

Beyond that, the company said that the results of a study conducted in collaboration with the Baylor College of Medicine (Houston) also extend the prognostic utility of the H/I ratio to untreated patients, who were also included in the study. The study is published in the October issue of the Journal of Clinical Oncology.

"Therefore, it has been established that the H/I ratio is a strong independent prognostic marker in patients with or without anti-hormonal treatment," the company said.

"The study with Baylor College of Medicine is the third in a series of clinical studies conducted to validate the clinical utility of the H/I ratio as a very significant prognostic biomarker in ER+ breast cancer patients," said Antonius Schuh, CEO of AviaraDx. "We are excited about the rapidly growing body of evidence supporting the clinical utility of HOXB13 and IL17BR in the prediction of breast cancer recurrence risk and expect additional clinical data to be published in the near future."

Schuh told D&IW that the "simplest way to understand what the test does in the personalized medicine setting is the diagnosis. If you are ER+, the clinician assumes that you have a relatively good prognosis. However, if you are high for the H/I . . . you simply don't behave like an ER+ patient. You resemble much more the [ER-] patients. That translates into certain conclusions, so we identify those 30% who have dysfunctional ER signaling that have a much worse prognosis than one would assume."

Schuh, former CEO at Sequenom (San Diego), said also that AviaraDx's test is "independent of tumor grade," whereas other tests on the market for cancer recurrence are simply "replacements for pathological tumor grade."

"Our H/I marker is independent of tumor grade . .. [and] it is information that you cannot obtain by any other means," he said.

While collaborations with such institutions as the Harvard Medical School/Massachusetts General (Boston) and Mayo Clinic (Rochester, Minnesota) continue, the H/I biomarkers, which is called the company's Breast Cancer Profiling (BCP) diagnostic technology, has been "licensed to a major reference laboratory," Schuh told D&IW.

AviaraDx also has two other so-called "first-in-class" molecular cancer profiling technologies: Molecular Cancer Identification (MCID) for improved cancer identification and classification, particularly in patients diagnosed with cancer of unknown origin, referred to as cancer of unknown primary (CUP).

"I think that personalized medicine in cancer starts [when] you get your personal diagnosis," Schuh said. "There are about 100,000 metastatic cancer patients that do not get a diagnosis . . . and they're suffering from metastatic cancer and they don't know what kind. Of course, that is quite a desperate situation."

Additionally its CUP test is licensed in the U.S. to Quest Diagnostics (Lyndhurst, New Jersey) and LabCorp (Laboratory Corporation of America; Burlington, North Carolina). It is also licensed to Agendia (Amsterdam, the Netherlands), a "CLIA-like" lab in that country that has "processed quite a few samples."

That CUP test was highlighted in a New England Journal of Medicine article in September, specifically focusing on how the test worked to determine the specific cancer in a pregnant woman with CUP.

"It's quite an exciting test," Erlander said.

AviaraDx is the remaining company from what was once Arcturus Bioscience (Mountain View, California) which sold off its life science business last year.

AviaraDx, which its chief scientific officer described as a "technology lab," is focused exclusively on developing and commercializing molecular diagnostic technologies for personalized medicine in cancer.