Concordance between the progesterone receptor isoform ratio in primary breast cancer and in matched axillary metastasis

MARIA FLORENCIA ABASCAL; ANDRES ELIA; GABRIELA PATACCINI; PAOLA ROJAS; SILVIA VANZULLI; MARCOS LIGUORI; PEDRO GONZALEZ; ALEJANDRA RAVA; PAULA MARTINEZ VAZQUEZ; JAVIER BURRUCHAGA; HUGO GASS; CLAUDIA LANARI

Congreso; Reunión Conjunta de Sociedades de BioCiencias; November 14-18, Mar del Plata, Buenos Aires, Argentina; 2018

Two thirds of breast cancer (BC) patients express estrogen receptorsalpha (ERα) and progesterone receptors (PR). Antiprogestinsmay 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) inducedtumor regression in experimental models with PRA levelshigher than those of PRB but it may increase the growth of thosewith the opposite profile.In our ongoing clinical trial (MIPRA NCT02651844), the inclusioncriteria to select patients to receive MFP treatment is based on thePR isoform ratio evaluated in the biopsy. Since endocrine treatmentis administered as an adjuvant treatment to target undetectable metastaticfoci, we decided to evaluate the concordance of PR isoformratio between primary tumors and axillar metastases.Matched primary tumors and axillary metastasis were obtained atsurgery 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 (PRBhigh) when PRA/PRB ≤ 0.83, equimolar (EQUI) when ratios werebetween 1.2-0.83, and PR negative (NEG). The percentage of PR+cells was determined by Immunohistochemistry (IHC).When comparing the PR isoform ratio of the 22 pairs a 91% of concordanceand a Kappa Coefficient of 0,85 (N= 22, p< 0.01) wasfound. The primary tumors of the two discordant pairs were categorizedas 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 primarytumors and in their axillary metastases. MFP might be used asan effective adjuvant treatment in PRA-H BC patients together withstandard endocrine therapy