Secretory Breast Carcinoma in A Six-Year-Old Girl: Case Report With Genetic Insights and Therapeutic Implications
Abstract
Background
Secretory breast carcinoma (SBC) is an extremely rare subtype, accounting for ~1% of breast cancers but representing the most common malignant breast tumor in pediatric patients. Although generally indolent, SBC carries a risk of local recurrence even decades after treatment. Its defining molecular hallmark is the ETV6-NTRK3 fusion.
Case Presentation
We describe a previously healthy six-year-old girl who presented with a 10 × 10 mm retroareolar breast mass. Histopathology revealed lobular tumor architecture with microcystic, cribriform, and tubular patterns, PAS-positive secretory material, and pronounced mitotic activity. Immunohistochemistry demonstrated positivity for S-100, MUC4, EGFR, and GATA3, with partial ER expression (20%), PR negativity, and HER2 negativity. Due to margin involvement after excisional biopsy, a simple mastectomy with sentinel lymph node biopsy was performed, followed by axillary dissection after six months for suspicious lymph nodes, which proved benign.
Genetic Findings
Germline testing (BRCA1/2, TP53, PTEN, CHEK2, PALB2, and others) was negative, excluding hereditary predisposition. Tumor profiling confirmed the canonical in-frame ETV6-NTRK3 fusion (ETV6 exon 5 – NTRK3 exon 13).
Therapeutic Implications
The presence of ETV6-NTRK3 not only confirms the diagnosis but also identifies a potential therapeutic target. TRK inhibitors (larotrectinib, entrectinib, repotrectinib) are FDA/EMA-approved for pediatric and adult solid tumors with NTRK fusions and have demonstrated high and durable response rates.
Outcome
Six years after surgery, the patient remains disease-free without evidence of recurrence or metastasis.
Conclusion
This case highlights the importance of integrating histopathology with molecular profiling in pediatric SBC. The identification of ETV6-NTRK3 provides diagnostic specificity and offers a precision oncology option in the event of relapse. Long-term surveillance and multidisciplinary follow-up remain essential for optimal care.
© 2026 A Vlahović, S Nikolić, S M Djuričić, D Dunđerović, N Ilić, A Sarajlija, M Denčić Fekete, A Cvetinović, M Vasić, published by Macedonian Academy of Sciences and Arts
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