Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019

PURPOSE Genetic testing is important for breast and ovarian cancer risk reduction and treatment, yet little is known about its evolving use. METHODS SEER records of women of age >= 20 years diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia were linked to the results of clinical germline testing through 2019. We measured testing trends, rates of variants of uncertain significance (VUS), and pathogenic variants (PVs). RESULTS One quarter (25.2%) of 187,535 patients with breast cancer and one third (34.3%) of 14,689 patients with ovarian cancer were tested; annually, testing increased by 2%, whereas the number of genes tested increased by 28%. The prevalence of test results by gene category for breast cancer cases in 2017 were BRCA1/2, PVs 5.2%, and VUS 0.8%; breast cancer-associated genes or ovarian cancer-associated genes (ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53), PVs 3.7%, and VUS 12.0%; other actionable genes (APC, BMPR1A, MEN1, MUTYH, NF2, RB1, RET, SDHAF2, SDHB, SDHC, SDHD, SMAD4, TSC1, TSC2, and VHL) PVs 0.6%, and VUS 0.5%; and other genes, PVs 0.3%, and VUS 2.6%. For ovarian cancer cases in 2017, the prevalence of test results were BRCA1/2, PVs 11.0%, and VUS 0.9%; breast or ovarian genes, PVs 4.0%, and VUS 12.6%; other actionable genes, PVs 0.7%, and VUS 0.4%; and other genes, PVs 0.3%, and VUS 0.6%. VUS rates doubled over time (2013 diagnoses: 11.2%; 2017 diagnoses: 26.8%), particularly for racial or ethnic minorities (47.8% Asian and 46.0% Black, v 24.6% non-Hispanic White patients; P < .001). CONCLUSION A testing gap persists for patients with ovarian cancer (34.3% tested v nearly all recommended), whereas adding more genes widened a racial or ethnic gap in VUS results. Most PVs were in 20 breast cancer-associated genes or ovarian cancer-associated genes; testing other genes yielded mostly VUS. Quality improvement should focus on testing indicated patients rather than adding more genes.

Automated summary

Genetic testing plays a crucial role in risk reduction and treatment for breast and ovarian cancer, but there are gaps in its evolving use, particularly in the increasing rates of variants of uncertain significance (VUS) and pathogenic variants (PVs). Testing trends show a gradual increase over the years, with a widening racial or ethnic gap seen in VUS results. In conclusion, there is a need for quality improvement in genetic testing to focus on indicated patients rather than simply adding more genes to the testing panel.