Abstract PD1-10: Multi-gene panel testing results in patients with multiple breast cancer primaries
Authors: Ross JL , Woodson AH , Gutierrez Barrera AM , Litton JK , Arun B 
Published: February 2018

Background: Every woman diagnosed with breast cancer has a risk to develop another breast primary throughout their lifetime. This risk is significantly elevated in individuals with a BRCA1 or BRCA2 mutation. For these individuals, the risk of a second primary breast cancer is 15% within 5 years of their initial cancer and the lifetime risk could be as high as 44%. Currently, the NCCN guidelines recommend testing of the BRCA1 and BRCA2 genes for individuals with multiple breast primaries, if their first diagnosis was under the age of 50. With the advent of Next Generation Sequencing and multiple gene panels, testing for hereditary breast cancer genes outside of BRCA1 and BRCA2 has become more prevalent. Although there are currently no guidelines that dictate when multiple gene panel testing should be ordered, recent studies have shown that there may be some associations between non-BRCA breast cancer genes such as ATM, CDH1, CHEK2, PALB2, PTEN, and TP53, in individuals with multiple primary breast cancers. Our study aimed to look at our institution's cohort of individuals with multiple primary breast cancers that underwent panel testing, to determine the rates of pathogenic mutations in non-BRCA genes.

Methods: Sixty-five patients that had multiple breast cancer primaries and underwent a multi-gene breast cancer panel test were identified using MD Anderson's Clinical Cancer Genetics Database. The genetic testing results for each of these patients was reviewed and analyzed.

Results: Out of the sixty-five patients found to have multiple breast cancer primaries and had a multiple gene panel test, 23 (29%) tested positive for a pathogenic mutation in a breast cancer predisposition gene: 6 (26%) BRCA1, 3 (13%) BRCA2, 4 (17%) ATM, 3 (13%) CHEK2, 1 PALB2 (4%), 1 PTEN (4%), 1 TP53 (4%). Overall, 15% of this cohort tested positive for a mutation in a non-BRCA breast cancer predisposition gene. The average age of first breast cancer diagnosis in these positive patients was 42 (range 26-75), which was similar to the average age in patients that tested negative or were found to have a variant of uncertain significance (VUS), 42 (range26-65). The average age of the first breast cancer diagnosis in patients positive for non-BRCA breast cancer genes was 46 (range 28-75).

Conclusion: In our cohort, 29% of patients with multiple breast primaries who underwent panel testing were found to have a germline mutation in a breast cancer predisposition gene. Interestingly, 15% of our cohort were found to have a mutation in a non-BRCA breast cancer gene. There was no difference between age of onset in those that tested positive versus those that tested negative or were found to have a VUS. The high positive rate for all individuals with multiple breast cancers, regardless of age, for both BRCA1/2 and non-BRCA genes suggests that panel testing for patients with multiple breast cancer primaries should be considered. This finding should be validated in larger cohorts in order to help clarify whether all patients meeting guidelines for BRCA1 and BRCA2 genetic testing due to multiple breast cancer primaries would benefit from a multiple gene panel test.

Citation Format: Ross JL, Woodson AH, Gutierrez Barrera AM, Litton JK, Arun B. Multi-gene panel testing results in patients with multiple breast cancer primaries [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD1-10.