Tsongalis, Gregory J.

We previously identified a +ACA polymorphism at ‐600 bp in the BRCA1 promoter that creates a FAC1 transcriptional repressor binding site. Subsequently, we performed a genotyping study to determine the prevalence of this BRCA1 promoter polymorphism among unaffected individuals and patients with breast disease. The genotypic distribution of the BRCA1 promoter was determined for 997 unaffected individuals and 763 patients with breast disease from the Mayo Clinic, UNC Hospitals, and the Carolina Breast Cancer Study. The BRCA1 promoter genotypic frequency among unaffected individuals was 481/997 (48%) WT/WT, 432/997 (43%) WT/ACA, and 91/997 (9%) ACA/ACA. The BRCA1 promoter genotypic frequency among patients with breast disease was 348/763 (46%) WT/WT, 343/763 (45%) WT/ACA, and 72/763 (9%) ACA/ACA. No differences were noted in the genotypic distribution of the BRCA1 promoter among patients with DCIS, BRCA1 mutation, suspected BRCA1‐related cancer (BRCAx), or sporadic breast cancer. The allelic frequency of the +ACA BRCA1 promoter polymorphism among breast disease groups [343/415 (83%) WT/ACA and 72/415 (17%) ACA/ACA] were not different than the allelic frequency of the controls [432/523 (83%) WT/ACA and 91/523 (17%) ACA/ACA]. Our results suggest that the +ACA BRCA1 promoter polymorphism occurs commonly, and may contribute to breast cancer upon activation of the FAC1 repressor protein. Support: NIH CA78343.

e22093 Background: Biomarkers are an integral part of cancer care. A variety of testing methods exist, allowing institutional selection of which technologies to use and in what order to run them. This descriptive study provides a benchmark on methods used in practice for biomarker testing in breast (BC), gastric/esophageal (GC), and non-small cell lung cancers (NSCLC). Methods: We conducted an IRB-approved web survey of the 58 NCI designated cancer centers (pathologists and oncologists) providing adult care in BC, GC, and NSCLC. We developed a survey instrument with 14 BC, 5 GC, and 10 NSCLC items asking about methods used, order of testing, turn around time (TAT) and if tests are internally developed (ID). Results: For BC, 32% (18/57) of sites run concurrent rather than reflex HER2 FISH and IHC testing, citing quality assurance reasons. Average TAT for concurrent vs reflex testing is 6.5 and 9.5 days. Rates of ID tests are 14% (8/57) for PgR, 12% (7/57) for ER and 7% (4/57) for HER2. For GC, 39% (21/54) of sites run concurrent HER2 FISH and IHC tests, citing reasons of quality assurance and evolving guidelines. TAT for concurrent vs reflex testing is 6.3 and 9.5 days. 19% (10/54) of sites use ID HER2 tests. All reporting sites use EGFR and ALK testing in NSCLC and 96% use KRAS. 24% (13/55) of sites run them concurrently with an average TAT of 7.6 days, while the average TAT for sites with sequential testing is 22.8 days. CAP recommends a 10 day TAT for NSCLC tests, and 92% (12/13) of sites with concurrent testing meet this guideline vs only 11% (4/38) of sites with sequential testing (p<.0001). Rates of ID tests are 57% (30/53) for KRAS, 47% (26/55) for EGFR and 35% (19/55) for ALK, for which a kit is listed on the FDA drug label. There is a difference in the use of ID tests between BC and NSCLC, p<.0148. Conclusions: Concurrent testing for BC and GC HER2, and for NSCLC markers is a common practice at NCI cancer centers; and it improves TAT. Concurrent NSCLC testing allows meeting CAP TAT guideline, but sequential testing does not. New markers (GC HER2, EGFR, KRAS and ALK) are commonly adopted, with a higher rate of internally developed tests than for BC HER2. [Table: see text]