Breast cancer (BC) is an important cause of morbidity and mortality. Most BC are hormone-receptor positive and can be treated with endocrine treatment (ET), until resistance or toxicity is developed. Specifically, H3K27m3, an epigenetic marker of gene repression, has been associated with prognosis in ET resistant BC. Herein, we aim to further understand its potential role as predictive marker of ET resistance before exposure to treatment.
A cohort of BC patients diagnosed between 1995 and 2002 at our institution were enrolled after informed consent. Expression of H3K27me3 was determined by immunohistochemistry (IHC) in formalin fixed paraffin embedded tissues. GenASIsTM software was used to assess cell-positivity using a custom profile from positive control. Pre-specified conditions: ≥ 5 frames ≥ 3000 cells analyzed/case. SPSS v24 was used for statistical purposes.
A total of 102 cases were assessed for H3K27me3 immunoexpression. Median of 6 frames/case (range 5-10) and 3311 cells/case (range 3017-5292) were obtained. Of the total cases analyzed, a median of 80% of cells showed positivity (range 9-100%). Using a negative/positive 50% cut-off, 81% were considered positive (pos.). The analyzed cohort displayed a median age of 60 years (33-82 years), 89% were classified as ductal carcinoma (DC) and 38% were grade 3. Concerning IHC subtyping, 43% classified as Luminal A-like, whereas 57% Luminal B-like. Around 66% of the cases evaluated for H3K27me3 expression were treated with adjuvant Tamoxifen exclusively. BC cases with H3K27me3 50-60% positivity were associated with higher cancer-related death (CI 95% 1.10-34.38, p = 0.05), although not reaching significance. Grade 3 BC significantly associated with increased risk of death (p = 0.024). An intermediate H3K27me3 expression (60-70% pos.) was observed in non-DC BC (CI 95% 1.42-13.92, p = 0.04).
In this preliminary retrospective cohort, H3K27m3 positivity was not found to be a pre-treatment endocrine resistance biomarker. However, statistical trends were observed between H3K27m3 expression and increased cancer-related death risk. Thus, further studies with extended cohort of patients are warranted.
Clinical trial identification
Legal entity responsible for the study
Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
All authors have declared no conflicts of interest.