ER-/PgR+ breast cancer is a separate entity characterized by distinct phenotype: Comprehensive reevaluation of cases from Polish and Hungarian centers.

Abstract

e12554 Background: ER negative (-)/PgR positive (+) breast cancer (BC) is very uncommon and questioned by many experts. We comprehensively reevaluated ER-/PgR+ BCs in the large cohort from Polish and Hungarian centers. Methods: FFPE blocks from 105 ER-/PgR+ tumors (45 breast biopsies and 64 post-operative samples from tumors not exposed to systemic therapy) were collected from 10 Polish and 3 Hungarian centers. In 60 cases available original slides with ER/PgR staining underwent reevaluation by 3 pathologists (MK, RP, WB) for ER and PgR expression by ASCO/CAP criteria. Subsequently, all samples were stained with 3 antibodies against ER (Dako monoclonal (MC) mouse anti-ERα, clone 1D5; Dako MC rabbit anti-ERα, clone EP1; VENTANA Roche MC rabbit anti-ERα, clone SP1), and PgR (Dako MC mouse anti-PgR, clone 636). If available, > 1 tissue block was used (av. 2.04 blocks/case, range 1-6). In 5 cases ESR1/PGR/ERBB2/MKi67 mRNA was measured by the Xpert® Breast Cancer STRAT4 (Cepheid, Sunnyvale, CA, USA). Results: 13 cases were excluded from immunohistochemical steps of the study due to insufficient amount of tissue and 8 - due to misdiagnosis after ER/PgR reevaluation of original slides. After re-staining, 42 cases (41.5%) retained the original phenotype, in 34 (33.67%) the ER status was corrected to ER+, and 16 (15.84%) tumors were ER/PgR-double-negative. The general agreement between anti-ER clones was moderate (Fleiss’ κ = 0.54). There were 56 ER- and 16 ER+ cases across all three assays. Five cases showed ER positivity with 2 antibodies (either SP1/EP1 or SP1/1D5), 5 tumors reacted exclusively with SP1 clone, and 2 - with 1D5 clone. Xpert Breast Cancer STRAT4 confirmed the ER-/PgR+ phenotype in 4 of 5 analyzed cases. The confirmed ER-/PgR+ BCs were characterized by lower percentage of PgR+ cells (median 5%) than BCs reclassified to ER+ (median 70%) (p = 0.022) and higher Ki67 expression than ER+ cases (median 54.5% vs 25%, respectively; p = 0.003). 39 (92.85%) ER-/PgR+ BCs presented with grade 3. Besides “conventional” high-grade cancers, we identified two distinct morphologies of ER-/PgR+ BC: resembling apocrine carcinoma (n = 5, 11.9%) and carcinoma with central acellular zone (n = 4, 9.5%). Conclusions: ER-/PgR+ BCs confirmed in the current study were defined by high-grade histology, high proliferation index and low percentage of PgR+ cells. We postulate ER-/PgR+ BC is a real albeit rare entity, and its diagnosis should be made cautiously, utilizing retesting with an alternative tissue block and anti-ER antibody.