Implementation and Audit of Mainstream Genetic Testing Within a High-Volume UK Breast Unit for Pathogenic Variations...

It is estimated that 5%-10% of patients who develop breast cancer have a causative inherited pathogenic or likely pathogenic variant (P/LP variant). In 2020, the UK National Test Directory published criteria for mainstream genetic testing for breast cancer patients (R208) and, subsequently, eligibility criteria to determine which patients are eligible for gene testing and PARP inhibitor treatment (R444.1).

Using the clearly defined criteria from NHS genomics, eligibility for testing under R208/R444.1 was determined for all patients diagnosed with breast cancer between March 2021 and March 2025. Eligible patients were offered genetic testing. Incidence of P/LP variants and impact on treatment were examined.

A total of 1812 patients had new DCIS/invasive breast cancer diagnoses, 255 were eligible for testing and 196 consented. Of these, 28 patients (14.3%) had a P/LP variant. Eight of these patients were eligible only using family history criteria. Twenty-one patients were eligible for breast conservation surgery. Preoperative genetic results were available for 13: eight patients opted for bilateral mastectomy rather than breast conservation. Where results were available postoperatively, three of eight patients who had breast conservation are planning bilateral risk reducing surgery. Three women newly diagnosed with a BRCA variant received a PARP inhibitor. Eligibility assessment for testing was time-consuming for trained clinicians.

14.3% of patients eligible and tested for a breast cancer-related hereditary P/LP variant were positive, which aligns with the expected number predicted by Genomics England. Family history scoring is an important element. Positive results were associated with changes in surgical decision-making for 14 women and enabled 3 patients to receive a PARP inhibitor.