Myriad Genetics recently presented data from a study on its homologous recombination deficiency test at a major medical conference, showing that the next-generation sequencing assay could accurately predict which triple-negative breast cancer patients would respond to the chemotherapy cisplatin.
In the study, presented at the San Antonio Breast Cancer Symposium earlier this month by researchers from Myriad, HRD test score predicted with a sensitivity of 100 percent all triple-negative patients who had a complete response to platinum chemotherapy before surgery. Additionally, the researchers concluded that the test score can predict drug response in all breast cancer subtypes, not just for triple-negative breast cancer patients.
Myriad's NGS-based HRD test gauges germline and somatic BRCA1/2 gene mutations, as well as a number of other markers involved in DNA repair. In a poster presentation at SABCS, researchers led by Kirsten Timms and others from Myriad evaluated 213 invasive breast tumor samples and matched normal tissue samples spanning all breast cancer subtypes defined by estrogen receptor, progesterone receptor, and HER2 status. In the study, researchers detected somatic and germline BRCA1/2 mutations "at significant levels" and depending on the breast cancer subtype, the frequency of mutations ranged from 7.8 percent to 16.4 percent.
However, BRCA1 promoter methylation showed up most frequently in triple-negative cancers, and BRCA deficiencies were present in 36 percent of triple-negative tumors compared to 10 percent in estrogen receptor-positive, HER2-negative cancers.
Myriad's HRD test provides three scores based on whole-genome tumor loss of heterozygosity (LOH) profiles, telomeric allelic imbalance (TAI), and large-scale state transitions (LST). According to Jerry Lanchbury, Myriad's chief scientific officer, the company developed the HRD test initially with the LOH score, but came up with the two other scores in the past year. With the addition of the TAI and LST scores, the company is hoping to increase the sensitivity of the test ahead of commercial launch for platinum therapies in 2015 and for PARP inhibitors in 2017.
All three scores are "highly correlated" with defects in BRCA1/2 and other pathway genes in breast or ovarian cancer, and can predict whether patients will respond to platinum agents, Timms and colleagues note in their SABCS abstract. "In this dataset all three scores showed significant association with BRCA1/2 status for the entire dataset," and "significant association was observed between the scores and BRCA1/2 status in each of the individual tumor subtypes," they reported. "The three scores were found to be highly correlated with one another, but all three were still significant in multivariate."
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At the moment, Myriad has two publicly announced partnerships with drug developers using the HRD test to identify best responders to investigational drugs. PharmaMar is studying Myriad's HRD test in a Phase II trial of PM1183, an agent that causes double-stranded DNA breaks to kill cells. BioMarin is also using it to investigate how different tumor types respond to the PARP inhibitor BMN-673. The company also has two undisclosed companion diagnostic partnerships involving the HRD test.
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