SAT-038 Bard1, A New Link Between Prolactinoma And Breast Cancer? Dilemmas Of Genetic Testing

Abstract Disclosure: B.S. Soares: None. V. Simas: None. T. Silva: None. T. Smith: None. A. Abreu: None. Introduction Prolactinomas are the most common pituitary adenomas, with giant prolactinomas (≥4 cm) being rare, more frequent in men, and often aggressive. Their genetic basis is not well understood. BARD1, a tumor suppressor involved in DNA repair through BRCA1 interaction, is associated with breast and ovarian cancers. We present a case of a young male with an aggressive prolactinoma harboring a germline BARD1 variant of uncertain significance. Case Report A 27-year-old male presented with absent pubertal development and hypopituitarism. Serum prolactin was markedly elevated at 14,000 ng/mL. He reported chronic headaches and denied visual field defects. Brain MRI revealed a 5.9 cm pituitary adenoma compressing the optic chiasm. Transsphenoidal resection was performed, and pathology revealed a lactotroph adenoma with necrosis, 5 mitoses/10 HPF, and a Ki-67 index of 4.7%. Postoperative prolactin remained elevated (486.5 ng/mL); cabergoline was initiated and gradually increased beyond 3 mg/week to achieve hormonal control. OncoPanel, a gene panel designed to detect mutations in 447 genes, copy number variations (CNVs) and structural variants, identified a germline BARD1 c.2282G>A (p.I738V) missense variant in this patient. The variant is classified by OncoPanel as Tier 2 (variant with potential therapeutic implications), however, the lack of functional validation precludes a definitive classification. Polysomy of chromosomes 3, 7, 9, 12, 19, and 20, and single-copy losses on chromosomes 6p and 13q were identified, indicating genomic instability. Discussion Germline variants are found in approximately 14% of the macroprolactinomas in the pediatric population. Genes associated with breast cancer, such as ESR1, PRLR, and SF3B1, have been identified in aggressive prolactinomas. CHEK2, a moderate-risk breast cancer-associated gene, and BRCA1 germline mutations have been linked to pituitary adenomas, reinforcing the connection between breast cancer-associated genes and pituitary tumorigenesis. The lack of pubertal development in this patient indicates an early presentation of the prolactinoma, and the identification of a germline BARD- involved in BRCA1-mediated repair- can be associated with this occurrence. It is often difficult, in clinical practice, to determine the association of variants identified in genetics studies with the phenotype. Another challenge is to determine if the identified CNVs causing loss and gain of some genes are associated with tumorigenesis or a consequence of cell proliferation. Nonetheless, high CNV indicates a more aggressive tumor behavior.Conclusion Given the association of breast cancer-associated genes with pituitary tumors, the BARD1 variant may be involved in the tumorigenesis of this prolactinoma. Additional studies are needed to clarify the role of BARD1 in pituitary tumorigenesis and its potential clinical relevance. Presentation: Saturday, July 12, 2025