Abstract P6-04-11: The foundation one assay influences clinical decision making in metastatic breast cancer
Authors: Harnden KK , Kimmick GG , Marcom PK , Westbrook KE , Blackwell KL 
Published: May 2016

Abstract
Background:
Tumor DNA sequencing is now readily available in metastatic breast cancer (MBC). The purpose of this study was to determine the effect of molecular testing on clinical decision-making in MBC at an academic cancer center.
Methods:
We obtained the Foundation One (FO) tests that were requested from Duke Cancer Institute breast oncologists between 12/2013 and 4/2015. We examined the following: ER/PR/HER2 status, histology, biopsy site and time, #months (mons) from time tissue was obtained to testing, #lines of prior therapy prior to tissue sampling and FO testing, #mons from initial diagnosis/MBC to FO. The following variables from the FO test were abstracted: #genomic alterations, #rx with potential benefit, #clinical trials available, #variations of unknown significance (VUS). Physicians were retrospectively surveyed regarding influence of FO results on clinical treatment decisions and on clinical trial consideration.
Results:
To date, 58 specimens have been sent for FO testing. From the time of FO testing, the mean #of mons since initial diagnosis (dx) was 84.4(7-435) and the mean #of mons since the dx of MBC was 31.4(1-140). Pts with triple negative breast cancer (TNBC) were more likely to have FO ordered within 1 year of MBC diagnosis (OR=2.93, p=0.048). On average, pts had received 3.78 lines of rx for MBC (0-10) at the time FO was sent. The timing of tissue acquisition for FO testing was bimodal (45% had a new bx for the assay whereas 55% had the FO test on archival bx). 50% of un-resulted (unsuccessful) FO assays were from archival tissue with a mean #mons since the archival tissue was obtained of 42 mons (18-74). To date, 56% of resulted samples were from archival tissue with a mean #mons since the archival tissue was obtained of 19.6(2-75).
Per the FO report: the mean #genomic alterations per pt = 6.21 (1-16); the mean #VUS per pt = 11.5 (3-30); the mean #mutation-directed rx per pt= 3.4 (0-15), the mean #mutation-directed clinical trials per pt= 9.33 (0-20). Genomic alterations occurring in ≥ 10% patients included: TP53 (48%), CCND1 (27%), FGF4 (27%), FGF19 (27%), FGFR1 (25%), PIK3CA (25%), FGF3 (25%), MYC (25%), ZNF703 (21%), ESR1 (19%), MCL1 (15%), CDH1 (13%), ERBB2 (10%), EMSY (10%), MYST3 (10%).
36 pts had invasive ductal carcinoma (IDC), 6 pts had inflammatory breast cancer (IBC), and 6 had invasive lobular carcinoma (ILC). No genomic alterations were associated with a sub-type of MBC with the exception of ESR1 mutations in ER+ IDC (100%) and CDH1 mutations in ILC (67%). Pts found to have ESR1 mutations had on average 63 mons(10-200) of endocrine therapy at the time of tissue sampling.
When the breast cancer medical oncology physicians were retrospectively surveyed, 42% FO assays influenced clinical treatment decisions and 14% resulted in clinical trial enrollment.
Conclusions:
FO utilization is variable based on MBC sub-type and the timing of tissue collection is bimodal. ESR1 mutations were associated with history of prolonged endocrine rx treatment in ER+ IDC and CDH1 mutations were associated with ILC. FO assays frequently influenced clinical treatment decisions but did not result in a high number of pts enrolled on clinical trials. We will update our dataset with additional FO assays and clinicopathologic variables.
Citation Format: Harnden KK, Kimmick GG, Marcom PK, Westbrook KE, Blackwell KL. The foundation one assay influences clinical decision making in metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-04-11.