Potential role of significant GATA3 mutation in male breast cancer responding to endocrine therapy

Abstract

A 60-year-old Chinese male with a hard mass, pressure pain, and ulcerous skin under his left axilla was first diagnosed with apocrine carcinoma, most likely metastasis from breast cancer. PET/CT scan detected multiple bone metastasis and enlarged lymph nodes at left axilla, mediastinal area 7, and left pulmonary hilus. Lumpectomy was performed to remove the mass followed by chemotherapy and radiotherapy against focal bone metastasis, left axillary lesion, and left subcutaneous chest wall. PET/CT examination showed progressive disease after the completion of the treatments. Two nontender hard nodules were noticed on the patient's left upper arm and multiple immobile nodules were palpated under his left axillary skin. Immunohistochemistry (HER2++, ER+, PR+, AR-) of the biopsy tissue combined with histopathology indicated invasive ductal carcinoma with neuroendocrine differentiation. Metastatic Luminal B subtype breast cancer was preferred. Anti-estrogen endocrine therapy was then performed and PET/CT scan showed partial remission after one month's fulvestrant administration. Two significant somatic mutations, AR R616H and GATA3 S408Afs*99, were detected in the biopsy tissue by next-generation sequencing. GATA3 is associated with estrogen receptor signaling and was identified as a driver gene of female breast cancer. However, the function of GATA3 in male breast cancer remains controversial. Report of this case hopefully will contribute to exploring the role of GATA3 mutation in molecular mechanisms and endocrine therapy of male breast cancer.