Concordance between circulating tumor DNA and tissue biopsy in patients with newly diagnosed recurrent breast cancer.

Abstract

1031 Background: Accurate determination of tumor origin and molecular subtype are recommended for patients with suspected recurrent breast cancer (BC). Circulating tumor DNA (ctDNA) provides a non-invasive alternative to tissue biopsy that offers identification of molecular tumor type (MTT) and molecular breast cancer subtype (MBS). This study aimed to assess the concordance between ctDNA and tissue biopsy in participants with suspected distant BC recurrence. Methods: This cross-sectional study evaluated patients with a previous history of primary BC who presented with suspected distant BC recurrence at least six months after initial BC diagnosis and underwent both tissue and liquid biopsy at enrollment. Blood samples were collected within 30 days before, or within 7-28 days after tissue biopsy and before any systemic or radiation treatment. Objectives were to assess concordance between tissue biopsy of the suspicious distant recurrent sites and liquid biopsy MTT and MBS (hormone receptor (HR)+/HER2−, HER2+ and triple negative BC (TNBC)). Patient blood samples were analyzed using the Guardant360 Liquid assay, reporting methylation-based prediction of MTT and MBS for samples predicted to be of BC origin. Results: A total of 120 patients (119 female, 1 male, median age 66 years) underwent biopsy a median 6.5 years after primary BC diagnosis. ctDNA was detected in 88% (105/120) subjects. Of these, 92% (97/105) yielded an evaluable MTT result with a high confidence score, with results as follows: Agreement between tissue pathology and ctDNA MTT was observed in 95 of 96 cases with diagnostic tissue pathology, including 99% agreement for breast cancer (88/89), and 100% agreement in lung adenocarcinoma (4/4), gynecological/ovarian (1/1), liver (1/1) and biliary (1/1). The non-diagnostic tissue biopsy was treated as BC by the oncologist. Among the 89 cases predicted BC by ctDNA, 88% (78/89) were evaluable for MBS while 2 did not have pathologic subtype available. In these 76 patients, positive predictive value for MBS predictions of HR+/HER2−, HER2+ and TNBC were 47/55 (85%), 6/11 (55%) and 8/10 (80%), respectively. Pathological tissue subtype of discordant HR+/HER2− cases were HER2+ (n = 7), TNBC (n = 1); of HER2+ cases were HR+/HER2− (n = 2), TNBC (n = 3) and of TNBC were HR+/HER2− (n = 2). Conclusions: Liquid biopsy demonstrated high agreement with tissue pathology for MTT classification, including identification of non-breast primary tumors. Differences in MBS classification between the two modalities warrant further investigation to assess potential contributing factors, including tumor heterogeneity.