Genetic testing for BRCA: Which NCCN criteria tell the tale?

Sep 09, 2019

Guidelines from the National Comprehensive Cancer Network (NCCN) list seven criteria for genetic testing in women with breast cancer.

Guidelines from the National Comprehensive Cancer Network (NCCN) list seven criteria for genetic testing in women with breast cancer. A new study sheds light on which of them are most likely to be linked with finding a BRCA mutation, an area in which data have been lacking.

Findings from the research, by investigators from the University of Iowa, were published in The American Journal of Surgery. They performed a retrospective chart review of patients with breast cancer who underwent BRCA testing based on NCCN guidelines, which list the following indications in such patients:

  • Family history of known deleterious BRCA1/2 gene mutation

  • Breast cancer diagnosis ≤ 45 years old

  • Breast cancer diagnosis ≤ 50 years old with an additional breast cancer primary

  • Breast cancer diagnosis ≤ 50 years old PLUS at least one close relative with pancreatic cancer OR at least one close relative with prostate cancer OR an unknown or limited family history

  • Breast cancer diagnosis ≤ 60 years old with triple negative breast cancer (TNBC)

  • Diagnosis at any age with ≥ 2 close blood relatives with breast, pancreatic or prostate cancer OR ≥ 1 close blood relative with breast cancer diagnosed at ≤ 50 years old OR ≥ 1 close blood relative with ovarian cancer OR a close male blood relative with breast cancer

  • A personal history of male breast cancer

The cohort study included 199 patients with breast cancer who underwent BRCA testing between January 2008 and July 2015. The authors hypothesized that some patients screened would be more likely than others to have a mutation detected and set out to determine which of the NCCN criteria were associated with higher rates of BRCA mutation.

With 98.5% adherence to NCCN guidelines, the majority of the patients (94%) were found not to have BRCA mutations and there were no significant differences between the mutation-negative and -positive patients in terms of age, race, or histologic type of breast cancer. Tumors in the patients with mutations were less likely to be estrogen receptor- (25% vs 66%; P = 0.003) or progesterone receptor-positive (25% vs 60%; P = 0.01). Among the patients with TNBC, three (8.3%) had BRCA mutations and three (8.3%) had a BRCA variant of uncertain significance.

In patients with BRCA mutations, the factors with the highest yield for that result were family history of the mutations (50%; P = 0.019), age ≤ 45 at diagnosis (9.7%; P = 0.034), and meeting three or more of the NCCN criteria (13.3%; P = 0.03). In multivariate analysis, an increased rate of BRCA mutation was associated with having a family history of that mutation and age ≤ 45. Overall, 42% of the patients met one NCCN criterion for testing, 31% met two criteria, and 22% met two or more criteria. The incidence of BRCA mutation was 2.4% in those who met one criterion versus 13.3% in those who met three or more criteria.

These results, the authors said, suggest that in the subset of patients who meet the NCCN criteria associated with higher rates of BRCA mutation, it may be prudent to wait for results of genetic testing to guide surgical management. They noted, however, that the generalizability of a retrospective and single-institution study is limited and a large, prospective, multi-institutional study is needed to confirm their findings.