Abstract P1-05-20: Comparing the frequency and types of genetic aberrations between older and younger women with metastatic breast cancer at the University of North Carolina at Chapel Hill
Authors: Jolly TA , Grilley-Olson JE , Deal AM , Ivanova A , Hayward MC , Benbow JM , Parker JS , Patel NM , Eberhard DA , Weck KE , Mieczkowski P , Dees EC , Muss HD , Reeder-Hayes KE , Earp HS , Sharpless NE , Carey LA , Hayes DN , Anders CK 
Published: March 2017

Background: Targeted therapies have the potential to revolutionize cancer treatment in older adults as they are often oral, convenient, may be better tolerated than cytotoxic chemotherapy, and can be tailored to an individual's biomarker profile. We explore the frequency and distribution of potentially actionable genomic alterations among older (≥65) and younger (&lt;65) patients (pts) with metastatic breast cancer (MBC).

Method: Next generation genetic sequencing (UNCseq™) of a dynamic panel of target genes was prospectively offered to pts with MBC treated at the University of North Carolina at Chapel Hill (UNC). DNA libraries were prepared separately from a retrieved archival FFPE tumor sample and a matched normal sample from each pt. Relevant targets were enriched by custom Agilent SureSelect hybrid capture baits using standard protocols. Samples were sequenced on Illumina HiSeq 2000/2500 platforms. Mutational findings were reviewed by a molecular tumor board; variants identified to be potentially actionable underwent confirmatory testing in a CLIA approved laboratory. Confirmed findings were inserted into the pt's EMR accessible by both the pt and the treating oncologist. Two-sided Fisher's exact test was used to compare percentages between age-specific groups.

Results: As of 3/31/16, results were available for 140 pts. 19% were 65 years or older. Breast cancer clinical subtypes were: HR+/HER2- 49%, HER2+ (HR any) 17%, TN 34% and metastatic location was: bone only 5%, visceral only 44%, bone & visceral 51%; no significant differences were observed between older and younger age groups. Older pts were more likely to be Caucasian compared to younger patients (92% v 75%, p=0.06). Overall, older patients had a higher total number of mutations compared to younger patients (see Table) (p=0.04). Mutation types were similar between age groups, although a trend for more PIK3CA mutations among older patients was seen (37% v 20%, p=0.07).

Observed Mutations by Age. ≥ 65 years (%) N=27&lt; 65 years (%) N=113pNumber of Mutations   01127.0414849.0423320.04374.04Type of mutation   PIK3CA3720.07CCND179.99NF-1115.37FGFR144.99PTEN49.69EGFR04.99

Conclusion: Genomic alterations may allow therapeutic tailoring in both older and younger patients with breast cancer. In this cohort with metastatic disease, older patients had significantly more mutations, but no clear difference in mutational types was seen by age. The relative small number of older pts in this cohort limits generalization, but supports the need for more extensive characterization of molecular aberrations among older pts with metastatic breast cancer in the new era of targeted therapy.

Research support by the University Cancer Research Fund, NCI Breast Cancer SPORE grant (CA58223), John A. Hartford Foundation and Susan G. Komen Foundation.

Citation Format: Jolly TA, Grilley-Olson JE, Deal AM, Ivanova A, Hayward MC, Benbow JM, Parker JS, Patel NM, Eberhard DA, Weck KE, Mieczkowski P, Dees EC, Muss HD, Reeder-Hayes KE, Earp HS, Sharpless NE, Carey LA, Hayes DN, Anders CK. Comparing the frequency and types of genetic aberrations between older and younger women with metastatic breast cancer at the University of North Carolina at Chapel Hill [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-20.