The Pros and Cons of a Patient’s HRD Score

The score has merit, but needs some refinement

• The homologous recombination deficiency (HRD) score helps predict a patient’s response to PARP inhibitors
• According to Dr. John Nakayama, a lack of standardization among diagnostic tests can complicate results
• Dr. Nakayama suggests refinements to the score should better predict which patients will benefit most

Homologous recombination deficiency (HRD) score is an emerging marker to predict an ovarian cancer patient’s response to PARP inhibitors. However, its use is complicated by a lack of standardization between the molecular diagnostic companies.

“The Myriad score and the Foundation score are not exactly the same thing,” Dr. John Nakayama, gynecologic oncologist at Allegheny Health Network, tells SurvivorNet Connect. “In Foundation, they use loss of heterozygosity to build their HRD score. Myriad uses three items…loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions.”

Those inconsistencies can lead to questionable results – as happened when Dr. Nakayama sent a patient’s tissue for three tests. “One was pathologic, one was maybe, and one was no,” he says.

Not all BRCA mutations are the same. “They can have different coding changes,” he says. Depending on the mutation and the database it’s compared against, the pathologic status can vary. Although Dr. Nakayama believes HRD scoring is worthwhile, “There are clearly some problems with it. We need to refine the score.”

He says refinements should help answer the question of not only which patients will benefit most from PARP inhibitors, but also who will achieve long-term progression-free survival. “There are some people that just go forever, and we need to figure out who those people are,” he says.