Abstract 300P
Background
Treatment options for metastatic breast cancer include endocrine therapies for hormone receptor positive (HR+) patients, Herceptin therapy for Her2+ patients and chemotherapy for TNBC (triple negative breast cancer) patients. While temporarily effective, these treatments are all undermined by the eventual emergence of resistance. We have used NGS-based liquid biopsy to profile genomic alterations in HR+, Her2+ and TNBC metastatic breast cancer patients during disease progression following first-line treatment, and report the emergence of distinct mutational patterns across clinical subtypes.
Methods
Blood samples from 159 metastatic breast cancer patients were collected at baseline prior to first-line treatment at the Beijing Cancer Hospital. Additional samples were collected from a subset of 31 patients at the time of disease progression. A targeted NGS-based liquid biopsy assay (PredicineCARE™) was used to profile somatic mutations and copy number variations across 152 genes in circulating tumor DNA.
Results
The most frequently detected alterations across all patients at baseline were TP53 (44%), PIK3CA (28%) and ERBB2 (25%). Across subtypes, Her2+ patients harbored a higher frequency of ERBB2 amplifications (70%) compared to HR+ (0%) (p = 1.1E-15) and TNBC patients (3%) (p = 3.5E-11), as well as a higher frequency of TP53 alterations (64%) compared to HR+ (31%) patients (p = 0.004). To survey the emergence of new alterations during metastatic progression across clinical subtypes, profiles were also generated at the time of disease progression. New alterations were detected in 7/11 (64%) HR+, 0/8 (0%) Her2+ and 2/12 (17%) TNBC patients at progression (p = 0.006). New variants in the HR+ group included ESR1, TP53, PIK3CA, CDKN2A, FGFR1, ERBB2, and PTEN alterations.
Conclusions
HR+ patients treated with endocrine therapies exhibited a much higher frequency and diversity of ctDNA-based alterations at the time of disease progression relative to HER2+ and TNBC patients receiving Herceptin and chemotherapy treatments, respectively. These patterns underscore the powerful selective pressure exerted by endocrine therapies, resulting in distinct resistance mechanisms.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Huidu Shanghai Medical Sciences Ltd.
Disclosure
T. Zheng X. Dong, B. King: Financial Interests, Institutional, Full or part-time Employment: Huidu Shanghai Medical Sciences Ltd. A. Wang: Financial Interests, Personal and Institutional, Full or part-time Employment: Huidu Shanghai Medical Sciences Ltd. P. Du, S. Jia, J. Yu: Financial Interests, Personal and Institutional, Ownership Interest: Huidu Shanghai Medical Sciences Ltd. All other authors have declared no conflicts of interest.