Concordance between the Progesterone Receptor isoform ratio in primary breast cancer and in matched axillary metastasis

ABASCAL MF; ELÍA A,; PATACCINI G; ROJAS P; VANZULLI SI; LIGUORI M; GONZALEZ P; RAVA A; MARTINEZ VAZQUEZ P; BURRUCHAGA J; GASS H; LANARI C

Mar del Plata

Congreso; Reunión conjunta SAIC SAI SAFIS; 2018

Two thirds of breast cancer (BC) patients express estrogen receptors alpha (ERα) and progesterone receptors (PR) and receive endocrine therapy. Antiprogestins may become a therapeutic approach to treat patients with PR+ tumors.The PR is expressed as two isoforms, isoform A (PRA) and B (PRB). Our lab demonstrated that the antiprogestin mifepristone (MFP) induced tumor regression in experimental models with PRA levels higher than those of PRB but it may increase the growth of those with the opposite profile.In our ongoing clinical trial (MIPRA NCT02651844), the inclusion criteria to select patients to receive MFP treatment is based on the PR isoform ratio evaluated in the biopsy of the primary tumor. Endocrine treatment is administered as an adjuvant treatment to target undetectable metastatic foci. This highlights the relevance of evaluating the PR isoform ratio of primary tumors and metastatic foci.The aim of this study is to evaluate the concordance of PR isoform ratio between primary tumors and axillar metastases.Matched primary tumors and axillary metastasis were obtained at surgery from BC patients from the Magdalena V Martinez Hospital, Buenos Aires (22 pairs). Samples were categorized by Western Blot (WB) as PRA-H (PRA high) when PRA/PRB ≥ 1.2, PRB-H (PRB high) when PRA/PRB ≤ 0.83, equimolar (EQUI) when ratios were between 1.2-0.83, and PR negative (NEG). The percentage of PR+ cells was determined by Immunohistochemistry (IHC). Concordance analysis was performed using the Cohen’s Kappa coefficient. When comparing the PR isoform ratio of the 22 pairs a 91% of concordance and a Kappa Coefficient of 0,85 (N= 22, p< 0.01) was found. The primary tumors of the two discordant pairs were categorized as PRB-H while the metastasis was PRA-H or NEG.In 43/44 samples PR status correlated in WB and IHC studies (Kappa= 0,91; p< 0.01).We conclude that similar PR isoform ratios are observed in primary tumors and in their axillary metastases. MFP might be used as an effective adjuvant treatment in PRA-H BC patients together with standard endocrine therapy.