In our BC study population of over 3000 patients, 7% of BC patients reported a family history of PC in a first or second degree relative. Genetic testing was completed in 56% of BC patients with FHPC, and 11.6% carried a PGV with clinical relevance. Genes linked to PC risk represented 60% of the findings (BRCA1, BRCA2, and PALB2), and these patients meet current published guidelines recommending PC surveillance with annual imaging beginning at age 50 or 10 years younger than the earliest diagnosis of PC in the family 5,6. Importantly, several BC patients without a family history of PC at the time of diagnosis also carried PGVs in genes linked to PC risk (BRCA2, ATM, CDKN2A, PALB2, and MLH1). All of these patients would benefit from follow up care that includes updating family history for new PC diagnoses that could impact care, as well as receiving information about changes in PC surveillance recommendations over time.
Our study found that changes in criteria for genetic testing, including expanded age range and added family history components, and the addition of multi-gene panel testing as a recommended approach have potential impact on a majority of BC patients. A substantial proportion of BC patients in the study population, 43% overall, had some type of genetic testing. This proportion is higher than was found in a recent population based analysis of BC patients 26, and could reflect the demographic characteristics of our study population which was 28% Ashkenazi Jewish, or differences in utilization at an academic hospital. Despite relatively high test utilization, 44% of BC patients with a family history of PC and 57% of those without family history of PC had no genetic testing of any kind. This lack of testing could be attributed to a variety of reasons, including not being referred for testing by treating physician 27–29, or declining testing for reasons including cost 28,29 or anxiety about potential second primary cancers and impact on future generations 30. Another possibility is that patients did not meet testing criteria at the time of the initial diagnosis. NCCN criteria for genetic testing and screening have evolved and expanded over time, and BC survivors could benefit from periodic re-assessment that considers current criteria along with any changes in the family history of cancer. Additionally, the performance of genetic testing guidelines, including NCCN and Medicare guidelines, have come into question with similar PGV detection rates in BC patients who met criteria compared to those who did not. 31,32 One study found that the sensitivity of NCCN criteria for genetic testing were improved from 70–90% by including all women with breast cancer diagnosed under age 65 33. Based on this data, the American College of Breast Surgeons put forth a statement in 2019 advocating for offering genetic testing to any BC patient, regardless of age or family history 34. This statement would have relevance for the 56% of BC patients in our study who had no testing at all.
Among those in our study who completed genetic testing, 62.6% (41% of those with family history of PC) had testing only for BRCA1 and BRCA2. This could reflect differences in available testing for patients seen 2014–2018 when multi-gene panel testing became more broadly available. This change was brought about by evolution in testing technology decreasing sequencing cost, along with a June, 2013 United States Supreme Court decision invalidating patents on the sequence of BRCA1 and BRCA2 35,36. One study of test utilization in BC patients showed a shift from 74% BRCA1/2 only in 2013 to 33.5% BRCA1/2 only by 2015 37. However, NCCN criteria as recently as 2016 continued to recommend specific syndrome testing as the preferred approach, with consideration of multi-gene panel testing only for patients negative for single syndrome testing and with a family history suggestive of inherited cancer risk. Multiple studies have documented additional relevant PGV findings in women with breast cancer offered multi-gene panel testing 38–41. As in our population, the most common genes beyond BRCA1/2 identified on multi-gene panels included several with links to PC risk. Current NCCN guidelines recommend consideration of multi-gene panel testing both as a first line test, and for patients previously negative for BRCA1/224. Genetics providers have attempted re-contact of patients via mail to notify them of updated testing, but subsequent test uptake has been very low 42,43. Integrating genetic services into cancer survivorship care could help to bridge this gap, and has shown efficacy in a pediatric survivor clinic setting 44.
The American Cancer Society and American Society of Clinical Oncology have developed guidelines for survivorship care that address multiple relevant issues for BC survivors including risk evaluation and genetic counseling, as well as screening for second cancers 1. These guidelines address the possibility that genetic counseling and genetic testing may not have been offered to a patient meeting criteria, or that family history may have changed leading to a patient meeting criteria who did not at initial diagnosis. In addition, other factors may change, including identification of new susceptibility genes or advances in testing technology, updates to genetic testing criteria, or changes in cancer screening recommendations for individuals with relevant PGVs or family history risk factors 45, suggesting the importance of ongoing repeated genetic risk assessment in cancer survivors 45. Our findings provide support for this recommendation.
The study has some limitations, including reliance on retrospective analysis of patient-reported family history, which may be incomplete, or may have changed to include new cancer diagnoses since the time of last data collection. This could result in misclassification of BC patients with and without family history of PC. For the purposes of data entry, “multi-gene panels” included testing for any gene(s) beyond BRCA1/2, and specific information about the number of genes analyzed was not documented. This could lead to under-identifying the number of patients who could benefit from updated testing.