Abstract P5-14-09: Comparison of cell-free DNA genomics of breast cancer associated-chest wall disease vs. age & subtype matched controls with metastatic breast cancer not involving the chest wall

Abstract Background: Breast cancer associated-chest wall disease (CWD) clinically behaves in an aggressive manner. However, little is known about the genomics of CWD. Cell-free DNA (cfDNA) can identify oncogenic mutations in metastatic breast cancer (MBC). We hypothesized that the cfDNA genomics of CWD may vary from MBC cases without CWD. We compared the cfDNA genomics of patients with CWD to that of age and subtype matched MBC controls without CWD. Methods: Patients with MBC at an academic institution who underwent cfDNA testing (Guardant360, next generation sequencing (NGS), 74 gene assay) from 2/2016-2/2021 were identified. Patients with documented CWD (chest wall recurrence with nodules, ulceration, and/or skin metastases on imaging and/or examination) at the time of cfDNA testing (coinciding with MBC diagnosis) were included in the CWD cohort. Age and subtype matched MBC controls without CWD (CON) during the same time period with cfDNA results at MBC diagnosis were identified. A retrospective review was conducted to determine clinical features and cfDNA genomics of CWD and CON. A two-sample test of proportions was used to compare CWD to CON, with p< 0.05 for statistical significance. Results: Thirty-one patients with CWD and 63 CON were identified. Both groups were well-matched in median age at MBC diagnosis (CWD 57 vs. CON 59 years, p=0.93) and subtype distribution (CWD: TNBC 35%, HR+/HER2- 58%, HER2+ 6%; CON: TNBC 29%, HR+/HER2- 65%, HER2+ 6%, p=0.78). Patients also had similar racial distribution in both cohorts (p=0.57). Ninety percent (28/31) of CWD vs. 90% (57/63) of CON had ≥1 mutation detectable in cfDNA (p=0.62). Median number of cfDNA mutations for CWD was 4.5 (range 0-16) vs. 4 (range 0-21) in CON (p=0.32). The most common cfDNA mutations in CWD were TP53 (58%), NOTCH1 (19%), PIK3CA (16%), BRCA1 (13%), NF1 (13%), FGFR2 (13%), ESR1 (13%), STK11 (10%), NTRK1 (10%), APC (10%), and KIT (10%). In comparison, the most common cfDNA mutations in CON were TP53 (54%), PIK3CA (35%), ESR1 (14%), GATA3 (13%), and ATM (11%). Table 1 depicts mutations that varied between CWD and CON which were statistically significant in ≥1 cohort analyzed. In HR+/HER2- MBC, NOTCH1, STK11, NTRK1, DDR2, and NF1 were significantly more common in CWD than CON. For TNBC, NOTCH1 was numerically more common in CWD vs. CON (p=0.06). Conclusions: The cfDNA genomic spectrum of CWD varies from MBC that does not infiltrate the chest wall. Mutations that are associated with metastasis (NOTCH1), inhibition of tumor suppression (STK11), tumor migration (DDR2), proliferation (NTRK1), and endocrine resistance (NF1) were significantly more common in HR+/HER2- CWD than matched controls. Further research is needed to validate these findings and determine the impact of matched targeted therapies for CWD. Table 1 N/A: mutation not observed Citation Format: Neelima Vidula, Lianne Ryan, Andrzej Niemierko, Dejan Juric, Steven J. Isakoff, Francys Verdial, Marjan Azin, Laura A. Petrillo, Beverly Moy, Leif Ellisen, Shadmehr Demehri, Aditya Bardia. Comparison of cell-free DNA genomics of breast cancer associated-chest wall disease vs. age & subtype matched controls with metastatic breast cancer not involving the chest wall [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-09.