In a study of germline genetic testing in women diagnosed with breast or ovarian cancer reported in the Journal of Clinical Oncology, Allison W. Kurian, MD, MSc, and colleagues found that undertesting persists in patients with ovarian cancer, and that most pathogenic variants are found in 20 breast cancer– or ovarian cancer–associated genes, with an increase in testing for additional genes being associated with increased identification of variants of uncertain significance.
Allison W. Kurian, MD, MSc
Study Details
The study used SEER (Surveillance, Epidemiology, and End Results) data from 187,535 women diagnosed with breast cancer and 14,689 diagnosed with ovarian cancer from 2013 to 2017 in California or Georgia, linked to results of clinical germline testing through 2019.
Key Findings
Overall, 25.2% of patients with breast cancer and 34.3% of patients with ovarian cancer were tested. The rate of testing increased by 2% annually, whereas the number of genes tested increased by 28% annually. Approximately 25% of tested patients with breast cancer diagnosed in early 2013 received multiple gene panel testing vs more than 80% of those diagnosed in late 2017. Among those with ovarian cancer, multiple gene panel testing was performed in approximately 40% of those diagnosed in early 2013 vs more than 90% diagnosed in late 2017.
For breast cancer cases diagnosed in 2017, the prevalence of test results by gene category were:
- 5.2% pathogenic variants and 0.8% variants of uncertain significance for BRCA1/2
- 3.7% pathogenic variants and 12.0% variants of uncertain significance for breast cancer– or ovarian cancer–associated genes (ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53)
- 0.6% pathogenic variants and 0.5% variants of uncertain significance for other actionable genes (APC, BMPR1A, MEN1, MUTYH, NF2, RB1, RET, SDHAF2, SDHB, SDHC, SDHD, SMAD4, TSC1, TSC2, and VHL)
- 0.3% pathogenic variants and 2.6% variants of uncertain significance for other genes.
For ovarian cancer cases diagnosed in 2017, the prevalence of test results were:
- 11.0% pathogenic variants and 0.9% variants of uncertain significance for BRCA1/2
- 4.0% pathogenic variants and 12.6% variants of uncertain significance for breast cancer– or ovarian cancer–associated genes
- 0.7% pathogenic variants and 0.4% variants of uncertain significance for other actionable genes
- 0.3% pathogenic variants and 0.6% variants of uncertain significance for other genes.
Among women with breast cancer, the proportion of tested patients with pathogenic variants in BRCA1/2 decreased from 7.5% in early 2013 to 5.0% in late 2017 (P < .001), whereas the proportion of pathogenic variants among breast cancer– or ovarian cancer–associated genes and other actionable genes increased from 1.3% to 4.6% and from 0.3% to 1.3%. The proportion with variants of uncertain significance only increased from 8.5% to 22.4%.
Among women with ovarian cancer, the proportion with pathogenic variants in BRCA1/2 decreased from 15.7% to 12.4% (P < .001), whereas the proportion of pathogenic variants among breast cancer– or ovarian cancer–associated genes and other actionable genes changed from 3.9% to 4.3% and from 0.3% to 2.0%. The proportion with variants of uncertain significance only increased from 8.1% to 28.3%.
Overall, variants of uncertain significance–only rates increased from 11.2% in 2013 diagnoses to 26.8% in 2017 diagnoses. In 2017, variants of uncertain significance–only rates were 42.4% in Asian, 36.6% in Black, and 27.7% in Hispanic women vs 24.5% in White women with breast cancer (P < .001). Variants of uncertain significance–only rates were 47.8% in Asian, 46.0% in Black, and 36.8% in Hispanic women vs 24.6% in White women with ovarian cancer (P < .001).
The investigators concluded: “A testing gap persists for patients with ovarian cancer (34.3% tested vs nearly all recommended), whereas adding more genes widened a racial or ethnic gap in [variants of uncertain significance] results. Most [pathogenic variants] were in 20 breast cancer–associated genes or ovarian cancer–associated genes; testing other genes yielded mostly [variants of uncertain significance]. Quality improvement should focus on testing indicated patients rather than adding more genes.”
Dr. Kurian, of the Departments of Medicine and Epidemiology & Population Health, Stanford University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
