From 5th August we will begin to report PALB2 variants in addition to BRCA1 and BRCA2 when testing for suitability to prescribe Olaparib/Talazoparib for treatment of breast cancer (R444.1).
Detection of genetic variants in PALB2 does not make patients eligible for these treatments, but does indicate a significantly increased inherited risk of cancer. These variants may make patients eligible for enrolment in clinical trials.
Non-urgent advice: Guidance on ordering
R208 may be a preferable referral route for many patients
The inherited breast cancer and ovarian cancer test (R208) is a more comprehensive test and should be ordered in preference to R444.1 as a first line test for eligible patients. Clinicians referring for R208 must indicate clinical urgency and impact of the test result.
Reducing need for further testing
In most cases, you should no longer need to order R208 following a negative result from R444.1. unless CanRisk-estimates a 10% or higher chance of detecting variants in the four additional genes (ATM, CHEK2, RAD51C, RAD51D).
Testing relatives
Where pathogenic or likely pathogenic variants are detected via either R444.1 or R208, the patient’s relatives should be offered testing for inherited variants to enable increased surveillance and consideration of risk reducing options. In these cases, please facilitate referral to Clinical Genetics.
This change is a response to guidance issued by the UK Cancer Genetics Group / Cancer Variant Interpretation Group UK informed by real world feedback gathered by them. The change is intended to ensure detection of relevant high penetrance gene variants, while informing use of PARP inhibitor treatment, and helping to meet expected turnaround times.