Clinical utility of hereditary cancer panel testing: Impact of PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D results on patient management and adherence to provider recommendations

Abstract

Background: Although management guidelines exist for several genes associated with a 2-fold to 5-fold increase in the relative risk for certain cancers, the value of testing for them remains controversial.

Methods: De-identified personal and family history data for 654 individuals with pathogenic variants (PVs) in PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and/or RAD51D were analyzed for pretest and post-test candidacy for guideline-recommended management of cancer risk. These individuals were invited to complete a survey about provider recommendations and their adherence.

Results: Twenty-four percent of CHEK2, ATM, PALB2, or NBN PV carriers were appropriate for consideration of annual breast magnetic resonance imaging screening before genetic testing, with the remaining 76% appropriate only after testing. No BRIP1, RAD51C, or RAD51D PV carriers were appropriate for consideration of risk-reducing salpingo-oophorectomy before genetic testing; 100% were appropriate only after testing. Seventeen percent of CHEK2 PV carriers were appropriate for earlier and more frequent colonoscopy before genetic testing, with the remaining 83% appropriate only after testing. Provider recommendations for annual breast magnetic resonance imaging, consideration of risk-reducing salpingo-oophorectomy, and earlier and more frequent colonoscopy were reported by 42%, 26%, and 66% of breast, ovarian, and colorectal cancer risk PV carriers, respectively, before genetic testing, versus 82%, 79%, and 81%, respectively, after testing. Nearly all respondents had planned or undertaken provider-recommended management.

Conclusions: Testing for PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D changed management for those carrying PVs. Provider recommendations were aligned with guidelines, and patients adhered to recommendations, both of which are critical for reducing both long-term cancer morbidity and mortality.

Keywords: breast cancer; cancer risk; colorectal cancer; hereditary cancer; ovarian cancer.

Figure 1

The study design is illustrated. The Myriad Women's Health's internal database was queried for individuals who tested positive for a pathogenic variant (PV) in PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and/or RAD51D. Management recommendations were retrospectively applied before and after genetic testing to the 654 individuals with PVs (blue box). All 654 individuals with PVs and 2 batches of 500 randomly selected individuals from more than 10,000 who tested negative for any variant ordered by their physician were invited to respond to the survey (yellow boxes). For PV‐negative individuals, survey access was disabled after 150 had completed it. One PV‐negative individual's responses were not used after it was found that they did not meet the qualification criteria.

Figure 2

Guideline‐consistent management recommended by providers, as reported by pathogenic or likely pathogenic variant (PV)‐positive and PV‐negative patients, both before (light purple bars) and after (dark purple bars) genetic testing, is illustrated. An asterisk indicates a significant difference in the proportion of patients reporting a provider management recommendation pregenetic testing and postgenetic testing (P < .05). MRI indicates magnetic resonance imaging; RRSO, risk‐reducing salpingo‐oophorectomy.

Figure 3

Adherence to provider‐recommended management, as reported by pathogenic or likely pathogenic variant (PV)‐positive individuals, is illustrated. Bars indicate that patients have already undergone the recommended management (dark purple bars), plan to undergo the recommended management in the future (medium purple bars), or do not plan to undergo the recommended management (light purple bars). MRI indicates magnetic resonance imaging; RRSO, risk‐reducing salpingo‐oophorectomy.