Abstract P6-02-04: Screen detected and interval cancers; genomic analysis points to different molecular etiology?

Abstract

Abstract Breast cancers diagnosed after a negative mammogram but prior to the next screening episode are termed "interval cancers" and comprise as many as 25% of all cancers detected in women attending population-based screening programs. The high interval cancer rate is a major problem affecting the effectiveness of mammographic screening. It is unclear whether interval cancers represent a distinct biological entity compared to screen-detected cancers or whether their designation is simply an arbitrary outcome of screening timing. Using an Australian prospective population-based cohort of over 53,000 women (lifepool), 537 cases of breast carcinoma (in situ and invasive breast cancer) were identified, of which 293 had known screening status at time of diagnosis. Pathology reports, mammographic density data, germline DNA and tumor tissue were available for analysis. Screen and interval cases showed no significant differences in mammographic density or PR status but there were trends towards higher proportions of ER negative and HER2 positive cases in interval cancers (p<0.1). Interval cancers also had a younger age at diagnosis (p<0.01), increased tumor size (p<0.01) and higher grade (p<0.01). Copy number analysis was performed on a subset of invasive breast cancer cases using OncoScan MIP arrays. No difference in the overall number of copy number aberrations or fraction of the genome altered were observed, however specific differences were noted between interval and screen detected cases. These included copy number changes on chromosomes 8 and 11. Analysis of germline DNA was performed using a panel sequencing approach of known breast cancer genes as well as lower-penetrance SNPs. Pathogenic mutations in BRCA1, BRCA2, TP53 and PALB2 were identified in 1/13 interval cases (in BRCA2), 1/66 screen-detected cases and 8/74 cases with currently unknown screen/interval status. Screen detected cancers may thus have a reduced contribution from high-penetrance predisposing variants. Citation Format: Gorringe KL, Hunter SM, Byrne D, Devereux L, Rowley SM, Elder K, Huynh R, Pridmore V, Hopper J, Kavanagh A, Mitchell G, Mann BG, Fox SB, Campbell IG. Screen detected and interval cancers; genomic analysis points to different molecular etiology?. [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 P6-02-04.