Journal Article

Genomic characteristics of triple negative apocrine carcinoma: a comparison to triple negative breast cancer

Jung, Hae Hyun, Cho, Soo Youn, Kim, Seok Won, Park, Yeon Hee, Im, Young-Hyuck, Cho, Eun Yoon, Lee, Jeong Eon, Kim, Ji-Yeon, Lee, Semin, Park, Sabin, Nam, Seok Jin, Ahn, Jin Seok, Chae, Byung Joo

2023

Overview

Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student’s t test, p  < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC ( p  < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC ( P  = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC ( P  = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC. Breast cancer: Genomic characteristics of rare subtype examined A comparative study reveals the distinctive genomic and clinical characteristics of a rare form of breast cancer, with implications for treatment. Apocrine carcinoma accounts for 1–4 percent of breast cancer cases. The molecular characteristics of a subtype known as triple negative apocrine carcinoma (TNAC) remain unclear. Ji-Yeon Kim at Sungkyunkwan University School of Medicine, Seoul, South Korea, and co-workers conducted genomic analysis on tumor samples taken from 73 TNAC patients. They compared the results to samples from 32 triple negative breast cancer (TNBC) in which the low expression of Ki-67, a marker protein for cancer proliferation, was similar to the TNAC patients. TNAC patients had different genetic mutations and a better survival outcome than TNBC patients with low Ki-67. Therefore, early-stage TNAC may not require chemotherapy after surgery. Further research into TNAC genomic characteristics is warranted.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group,생화학분자생물학회
• Subject: 38 / 38/39 / 45/23 / 45/91 / 692/308/2056 / 692/308/575 / 692/699/67/1347 / 692/699/67/69 / Biomarkers, Tumor - analysis / Biomarkers, Tumor - genetics / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast carcinoma / Breast Neoplasms - pathology / Carcinoma - genetics / Chemotherapy / DNA repair / ErbB-2 protein / Female / Genetic analysis / Genomic analysis / Genomics / Humans / Medical Biochemistry / Mismatch repair / Molecular Medicine / Oncogenes / p53 Protein / Patients / Stem Cells / Survival / Survival Analysis / Triple Negative Breast Neoplasms - genetics / Triple Negative Breast Neoplasms - pathology / 생화학