Test to identity which breast cancer patients will respond to platinum-based chemotherapy

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Published: 9 Dec 2015
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Dr Johnathan Lancaster - Chief Medical Officer of Myriad Genetics, Salt Lake City, USA

Dr Lancaster talks to ecancertv at SABCS 2015 about the myChoice homologous recombination deficiency (HRD) test that can detect when a tumour has lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors.

In the interview Dr Lancaster notes that HRD is a very good biomarker for response to DNA-damaging drugs in patients with triple-negative breast cancer (TNBC).

He talks about a pooled analysis of studies that found that patients with TNBC with HRD or who were HRD positive were far more likely than HRD negative patients to experience a pathological complete response (pCR) when treated with platinum-based chemotherapy. He also comments on using the HRD assay in current clinical trials of PARP inhibitors.

ecancer's filming at SABCS 2015 has been kindly supported by Novartis through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

Homologous recombination deficiency truly is a biomarker for response for patients with triple negative breast cancer to DNA damaging agents, specifically platinum. So homologous recombination is a normal process that cells use to repair their DNA; in the presence of a deficiency in that ability to repair DNA cells become far more prone to any agent that induces DNA damage. We can take therapeutic advantage of that to target therapies that use DNA as a target, DNA damaging capacity as a target, to identify patients that are most likely to benefit from those DNA damaging agents.

What types of chemotherapy have you been looking at?

The work to date and the pooled analysis that we’re presenting this year really focusses on patients with triple negative breast cancer, one of the breast cancers, as you know, that’s most difficult to treat, that have been treated with platinum agents.

What are the outcomes of this study?

Our work to date suggests that patients with triple negative breast cancer who have homologous recombination deficiency or who are homologous recombination positive have a far greater likelihood of a pathologic complete response to platinum than those that don’t with odds ratios of four to five.

How do you discover these patients?

These patients would be tested at the time of diagnosis, at any time we have a tissue specimen that can be analysed, we use formalin fixed paraffin embedded tissue to analyse the DNA fingerprint. We really look for scars in the DNA that are manifestations of the presence of homologous recombination deficiency.

Is there any connection with the PARP inhibitors?

Yes, indeed. We are working, in fact, very actively in the clinical sphere to identify opportunities to combine the homologous recombination deficiency assay as a biomarker for PARP inhibition response. Early work suggests that, as you imply, homologous recombination deficiency is a potent biomarker to identify patients who will benefit from PARP inhibition.

What are the clinical implications?

There are many clinical studies already in play, in fact we’re participating in the vast majority of PARP inhibition studies that are leveraging homologous recombination as a companion diagnostic. We’re very excited with that participation and our involvement and we hopefully will start to see a benefit to patients in the very near future.