By Doug Macron
Mira Dx this week announced that it has licensed from Yale University technology related to microRNA-disrupting genetic variants that can be used to predict a patient's risk of developing triple negative breast cancer.
Triple negative breast cancer is characterized by tumors that don't have estrogen receptors, progesterone receptors, or significant amounts of human epidermal growth factor receptor 2, according to the National Cancer Institute. As such, it cannot be treated with standard chemotherapeutics such as tamoxifen, which target these receptors.
According to Mira Dx, triple negative breast cancer accounts for approximately 15 to 20 percent of all cases of the disease.
“There is a real need for tools that can help women who have a family history of breast cancer to better understand their risk,” Mira Dx President and CEO Martin Van Verhoef said in a statement, adding that the company aims to have a test capable of determining risk of triple negative breast cancer available this year.
Stephen Miller, Mira Dx's chief commercial officer, told Gene Silencing News that this time line, however, could be impacted by the company's efforts to determine physician need for the test.
A 2011 launch “is the plan … [but] we're still looking into what [a test] would look like, indications … [and] what the value ... would be,” he said.
“We're talking to physicians to [see if there] is even a need for this,” Miller explained. “If there is a need, then exactly what [is a] physician looking for?”
There is “always the possibility” that Mira Dx will decided that the market for a triple negative breast cancer test isn't there, but “we happen to not think that's the case,” he added. “We think there is some value [in] … supplying additional information to physicians so that they can ... better handle patients.
“There's really not a lot of good risk factors for triple-negative breast cancers,” Miller said. A test would provide “another risk factor the doctor puts into the equation,” in addition to things like age and family history.
“We hope that cancer risk markers such as this marker will provide valuable information for the tens of thousands of women and families each year who are and may be affected by triple negative breast cancer,” Van Verhoef added in his statement.
Mira Dx already markets a test designed to identify women at increased risk of developing ovarian cancer based on a genetic variant that affects the miRNA let-7 (GSN 7/22/2010). It is based on work conducted at Yale by company co-founder Frank Slack, who also contributed to the research related to the triple negative breast cancer technology Mira Dx has acquired.
According to Mira Dx, its decision to ink the licensing deal with Yale was largely driven by data published last month in Cell Cycle that showed rare BRCA1 haplotypes are associated with triple negative breast cancer risk.
“BRCA1 coding sequence mutations are a well-known risk factor for breast cancer, yet account for less than 5 [percent] of all … cases yearly,” the paper's authors wrote. While most breast tumors resulting from these mutations are triple negative, the mutations are rare and account for between 10 and 20 percent of triple negative tumors, the paper's authors wrote. “These findings suggest that there may be additional inherited genetic factors associated with BRCA1 misexpression that could predispose individuals to breast cancer.”
In light of evidence showing that 3' untranslated region polymorphisms disrupting miRNA binding can be “functional and can act as genetic markers of cancer risk,” the researchers looked to see if polymorphisms in the 3' UTR of BRCA1 and haplotypes containing these functional polymorphisms were associated with breast cancer risk.
“We identified 3'UTR [single nucleotide polymorphisms] in our breast cancer patients, and then performed haplotype analysis with these variants and five SNPs surrounding the BRCA1 3'UTR to determine the association of these haplotypes with breast cancer, the Yale team wrote. “Doing so, we identified five haplotypes common in our breast cancer patients but rare in non-cancerous populations.”
Among these, one haplotype, rs8176318, was significantly associated with breast cancer among African Americans, who are disproportionately affected by the triple negative form of the disease, and appeared to be a
“genetic marker of risk most strongly for triple negative breast cancer compared to their ethnically matched controls.” Notably, the haplotypes were not associated with common BRCA1 coding mutations.
These findings “support the hypothesis that these identified rare BRCA1 haplotypes may represent new genetic markers of an increased risk of developing breast cancer, and likely represent non-coding sequence variations in BRCA1 that impact BRCA1 function and lead to increased breast cancer risk,” according to the Cell Cycle paper.
The data also provide evidence that rs8176318 is a marker for breast cancer risk for [African American] women, and is a marker for [triple negative] breast cancer,” the paper concludes.
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