MyChoice

HRD means that one of the mechanisms for repairing DNA damage is impaired in the tumour. MyChoice combines analysis of BRCA1 and BRCA2 changes with a Genomic Instability Score (GIS). A BRCA result alone does not cover all the information assessed by this test.

The test is considered for patients diagnosed with ovarian cancer whose doctor is assessing the use of PARP inhibitors. The result does not replace assessment of the tumour diagnosis, disease stage, previous treatment or indications for the specific medicine.

• BRCA1 and BRCA2 analysis — sequence variants and large gene rearrangements present in the tumour.
• GIS includes loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transitions (LST).
• Sequence variant analysis alone does not cover all causes of HRD. GIS assesses the genomic scars left by impaired DNA repair; it is not a direct test of epigenetic changes.

The report presents GIS status, tumour BRCA1/BRCA2 status and an overall interpretation. Reports from testing laboratories may differ in presentation.

A positive HRD result may be important when assessing PARP inhibitor treatment options. The doctor interprets both positive and negative results according to the clinical situation and the conditions for using the specific medicine. Treatment must not be started, stopped or ruled out independently on the basis of the HRD result alone.

A BRCA change found in a tumour may be inherited or confined to the tumour. This tumour test alone does not confirm inheritance; the doctor may recommend additional germline testing.

Tumour material is tested. Sample preparation is coordinated with the doctor and pathology laboratory; this is not a cheek-swab test performed at home.

Before tumour material is sent, the sample requirements, documents and testing conditions for the specific test version are agreed with PharmaDNA.

Myriad provides publications from the phase III PAOLA-1, PRIMA and VELIA trials and studies of HRD assessment in laboratories. Patient selection, treatment regimens and outcomes differ between these studies, so their results cannot be converted into a general prediction of individual treatment success.

PAOLA-1 investigated maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer who had responded to first-line platinum–taxane chemotherapy with bevacizumab. In this trial, the progression-free survival benefit was more pronounced in the HRD-positive tumour group, including tumours without a BRCA mutation.

• PAOLA-1, 2019: original publication
• Myriad for clinicians: full publication list
• Myriad: validation of testing in pathology laboratories
• Denkert study clinical summary

In the 2023 MyChoice clinician brochure, HRD is considered positive when either GIS or tumour BRCA status is positive. If both are negative, a negative HRD result is reported. This scheme explains the test result but does not itself determine treatment.

The PAOLA-1 and PRIMA graphs in the official 2023 brochure show comparisons between specific treatment groups. They distinguish disease progression and overall survival outcomes, follow-up periods and comparator treatment regimens. Percentages in the graphs are not measures of test accuracy or guaranteed benefit for an individual patient.

Current clinical recommendations and the indications for the specific medicine apply to treatment. Authorisations in other countries or service conditions stated in manufacturer documents do not in themselves determine their application in Lithuania.

• MyChoice clinician brochure, 2023 (PDF in English)

The MyChoice CDx Plus patient and clinician publications are provided below. They also describe the additional Plus panel, so the specific test version and its scope must be agreed before ordering.

In the example result in the patient brochure, information about additional panel genes is separate from clinically validated use for PARP inhibitor decisions. The test version and its scope must be confirmed before ordering.

• MyChoice HRD official page
• MyChoice CDx Plus patient guide, 2022 (PDF in English)
• MyChoice clinician guide, 2023 (PDF in English)

A doctor assesses whether the test is suitable and interprets the results. Contact PharmaDNA with practical questions about arranging the test.