Genomic landscape of secretory carcinoma of the breast with axillary lymph node metastasis

Objective: Secretory carcinoma of the breast (SCB) is a rare low-grade often triple-negative breast carcinoma. We aim to analyze the pathological and molecular features of 21 SCBs, especially the SCBs with axillary lymph node metastasis.Methods: The clinicopathological characteristics of 21 SCBs were reviewed. Breast biomarkers, Pan-TRK and ETV6 break, and ETV6-NTRK3 fusion were performed on all cases. Next-Generation Sequencing (NGS) was performed on two cases with lymph node metastasis.Results: 21 SCBs consisted of 2 men and 19 women aged 5-73 years (median 43 years), with a mean 2.1 cm (range 0.5-3.5 cm) tumor size. 90.1% (19/21) cases had mixed microcystic, solid, tubular, and papillary patterns. Pan-TRK and S100 are positive in 95% (20/21) and 90% (19/21) of cases, respectively. Tumor markers ER, PR, and HER2 expressions were 62% (13/21), 33% (7/21), and 0% (0/21). All cases showed ETV6 (21/21) rearrangement and ETV6-NTRK3 (11/11) fusion. 57% (12/21) of the cases had a balanced translocation and 38% (8/21) with unbalanced signals of ETV6. There was no clinical difference between balanced and unbalanced translocations in histological morphology and other prognosis factors. Furthermore, one case (#4) had a duplication of the ETV6 gene and presented axillary lymph node metastasis. NGS analysis revealed simple genomes, low tumor mutation burden, stable microsatellite sites, and single nucleotide polymorphism (SNP) heterozygous mutation in both SCBs with nodal metastasis.Conclusion: SCB is an indolent invasive carcinoma, even the cases with axillary lymph node metastasis, presenting simple genomes. Duplication of ETV6 cases may indicate lymph node metastasis.