Locally advanced breast cancer (LABC) poses complex management issues due to failure of response to chemotherapy and progression to local complications such as skin erosion, superinfection and lymphedema. Most cell line and animal models are not adequate to study LABC.

A patient-derived xenograft (IOWA-1T) from a patient with LABC was characterized for expression profile, short tandem repeat (STR) profile, oncogenic mutations, xenograft growth and response to therapy.

STR profile authenticated the cell line as derived from a human female. The primary tumor and derived xenografts were weakly ERα-positive (<5%), PgR-negative and HER2 non-amplified. Expression array profile compared to MCF-7 and BT-549 cell lines indicate that IOWA-1T was more closely related to basal breast cancer. IOWA-1T harbors a homozygous R248Q mutation of the TP53 gene and in vitro invasion assay was comparable to BT-549, and greater than MCF-7. IOWA-1T xenografts developed palpable tumors in 9.6±1.6 days, compared to 49±13 days for parallel experiments with BT-20 cells (p<0.002). Tumor xenografts became locally advanced, growing to >2 cm in 21.6±2 days characterized by skin erosion necessitating euthanasia. The SUMO inhibitor anacardic acid inhibited the outgrowth of IOWA-1T xenografts, while doxorubicin had no effect on tumorigenesis.

IOWA-1T is a novel cell line with an expression pattern consistent with basal breast cancer. Xenografts recapitulated LABC and provide a novel model for testing therapeutic drugs that may be effective in cases resistant to conventional chemotherapy.