Abstract P1-21-04: Comprehensive genomic analysis of synchronous bilateral breast cancer tumors

Abstract

Abstract Background: Only 1-2 % of all breast cancers present as synchronous bilateral breast cancers. These tumors may be clonally related or clonally independent. Previous analyses of synchronous bilateral breast cancers were limited by the small sample size and lack of comprehensive genomic analysis. Comparative analysis of genomic alternations in these tumors presents a unique opportunity to address the following important questions: (1) are bilateral breast cancers clonally related, and (2) do bilateral breast cancers carry molecular and genomic alterations unique from those of unilateral breast cancers. Methods: We examined synchronous left and right breast tumor samples from (16) patients collected from 1988 -1998, flash frozen, and stored at -80C in the OHSU Knight Cancer Institute BioLibrary, and 10 pairs of FFPE preserved synchronous tumors from the Kaiser Permanente NW Research Bank, collected between 2004 and 2011. These samples and matching patient demographics, clinical staging, and biomarker configuration were acquired and research conducted under IRB regulatory approval. Tumor sections were cut and tumor rich areas identified and macro-dissected. Genomic DNA was isolated and whole exon-sequencing performed. For Kaiser specimens, a benign axillary lymph node was used as a matched germ line control. Clonal relationships were determined based on distribution of somatically acquired mutations and copy number variations in the bilateral breast cancer pairs. Results: Two out of 23 synchronous bilateral breast cancers (tumors excised on the same date or within a short interval of time) are clonally related based on distribution of somatically acquired mutations and copy number variation. Two out of three metachronous bilateral breast cancers (tumors excised 6, 12 and 18 months apart) are clonally related. Each tumor of a clonally related bilateral breast pair may have a different biomarker configuration. The number of unique somatic mutations in bilateral breast cancers from four clonally related pairs, i.e. present only in tumors from one side but not the contralateral side, is small and ranges from 0 to 8. The number and distribution of somatically acquired mutations in this set of bilateral breast cancers is similar to those previously seen in unilateral breast cancers. Conclusion: To our knowledge, our study represents the largest collection of synchronous bilateral breast cancers to have received comprehensive genomic analysis. Synchronous bilateral breast cancers appear to have similar breast cancer associated mutations as have been reported with unilateral breast cancers. The molecular differences between clonally related bilateral breast cancers appears to be limited suggesting that study of these differences may reveal the molecular underpinning of breast cancer metastasis. Citation Format: Shiuh-Wen Luoh, Myron Peto, Betsy Ramsey, Carol Halsey, Timothy Butler, Paul Spellman. Comprehensive genomic analysis of synchronous bilateral breast cancer tumors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-21-04.