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Currently, there is limited
data on molecular differences in circulating tumor DNA (ctDNA) in patients with invasive breast lobular carcinoma (ILC).
The study analyzed data from patients with metastatic breast cancer who underwent ctDNA testing to assess genomic differences
in patients with ILC, invasive ductal carcinoma (IDC), and mixed tissue types.
The researchers retrospectively analyzed data from 980 breast cancer patients with detailed clinical data (121 ILC, 972 IDC, and 62 mixed tissue types) and compared the single nucleotide variant (SNV), copy number variation (CNV) and oncogenic signaling pathway
in the tissue samples.
Variant profiles of ctDNA in ILC, IDC, and mixed-tissue patients
ILC was significantly associated
with negative HR+ HER2 and low HER2 expression.
Patients with ILC had a higher SNV (p<0.
05)
compared to patients with IDC or mixed tissue type.
In multivariate analyses, HR+ HER2-negative ILC was significantly associated
with mutations in the CDH1 (OR 9.
4), ERBB2 (OR 3.
6), and PTEN (OR 2.
5) genes.
In the mixed tissue patient cohort, no CDH1 mutation
was detected.
Gene mutations in the PI3K signaling pathway are more common in patients with ILC (OR 1.
76).
In a separate cohort of nearly 7,000 patients with metastatic breast cancer, CDH1 co-mutated
significantly with targetable variants (PIK3CA, ERBB2) and endocrine resistance-associated mutations (ARID1A, NF1, RB1, ESR1, FGFR2).
In conclusion, the evaluation of ctDNA in this study revealed the differences in pathogenic variants and carcinogenic signaling pathways of breast cancer in different tissue types, which has guiding significance
for histological classification and precision medicine treatment.
Original source:
Andrew A.
Davis, et al.
Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer.
eBioMedicine.
November 01, 2022.
https://doi.
org/10.
1016/j.
ebiom.
2022.
104316
