Buenos Aires
Breast Cancer
Symposium

BA-BCS 2024

September 3 – 6, 2024

IFIBYNE Auditorium, FCEN-UBA

Poster No. 77

Subtyping breast cancer PDX: androgen and glucocorticoid receptors, EGFR and lineage markers

Gabriela Pataccini1, Luisa Ambrosio1, Paula Martínez Vázquez2, Javier Burruchaga2, Eunice Spengler2, Claudia Lanari1

1.Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina 2.Hospital Magdalena V de Martínez, General Pacheco, Buenos Aires, Argentina .

Presenting Autor:
Pataccini, Gabriela

Instituto de biologia y medicina experimental (IBYME)

Patient-derived tumor xenografts (PDX) are reliable models generated when tumor tissue is transplanted from patients into immune-deficient mice. Breast cancer PDX usually retain ER, PR, or HER2 expression as their parental tumors. Other nuclear receptors such as androgen (AR) and glucocorticoid receptors (GR), are currently being explored as therapeutic targets. Our goal was to characterize twelve PDX developed in our laboratory regarding AR, GR, phospho-PR (p-PR), lineage markers (CK5/6 and CK8/18) and EGFR expression, used to sub-classify triple-negative (TN) breast cancers (TNBC). ER+ PDX (BC-AR685, BC-AR707, BC-AR767 and BC-AR781) were AR+, GR+, EGFR-, and expressed luminal markers (CK8/18+). Interestingly, they exhibited low or null PR levels (except for BC-AR685) but were stained positive for p-PR (except for BC-AR767). BC-AR767 expressed HER2, and BC-AR781 acquired HER2 expression. Only one out of the 12 PDX was ER-, PR- and HER2+ (BC-AR474). These PDX expressed AR, EGFR, CK8/18 and p-PR. PDX BC-AR485 originated from a TN lymph node recurrence during chemotherapy, although the primary tumor was ER+. This PDX showed an intense CK5/6 and GR staining, and mild EGFR and p-PR expression. The remaining TN PDX (BC-AR546, BC-AR553, BC-AR631, BC-AR687, BC-AR775 and BC-AR815) expressed CK8/18. BC-AR815 also showed intense CK5/6 staining, whereas BC-AR687 showed CK5/6+ foci. BC-AR815 was the only AR- TN PDX. Strong AR staining in CK8/18+ tumors suggests they belong to the luminal androgen receptor positive (LAR) subtype. GR was co-expressed with AR in 3 out of 6 TN PDX. EGFR and p-PR were highly expressed in BC-AR553 PDX. In general, PDX and parental tumors showed similar patterns. These PDX are excellent tools for studying tumor progression and testing the combination of AR and GR ligands with standard or novel therapies. p-PR expression in PR-negative PDX, underscores the role of the PR pathway even in tumors considered as PR negative.