Princess Margaret Cancer Centre - University Health Network, Department of Medicine, University of Toronto, Toronto, ON, Canada
Francisco Emilio Vera-Badillo , Martin Chang , Gordana Kuruzar , Alberto Ocana , Arnoud J. Templeton , Bostjan Seruga , Mustafa Al-Mubarak , Robyn Goldstein , Philippe L. Bedard , Ian Tannock , Eitan Amir
Background: AR expression is a favorable prognostic factor in estrogen receptor (ER) positive and ER negative breast cancer. Here we explore the association between AR, Ki67, and the 21-gene recurrence score (RS). We hypothesized that ER-positive breast cancers with high AR expression will be associated with a low Ki67 and RS. Methods: Sequential patients with lymph node negative, ER positive and HER2 negative breast cancer who had surgery at Mount Sinai Hospital, Toronto between January 2010 and October 2013 and in whom the RS was requested were identified. Archival tissue was sectioned and stained for AR (AR441 clone, Dako) and Ki67 (MIB-1 clone, Dako) and then visualized by protein polymer (MACH4, Biocare) and DAB chromogen. AR was scored using the Allred system and Ki67 by manual count (using the Ki67 working group recommendations) by a single pathologist. Associations between RS and AR, age, grade, mitotic score, Ki67, and the extent of ER and progesterone receptor (PgR) expression were assessed using linear regression. Ki67 was assessed as a continuous and dichotomous variable (using a cut off of 14%). Statistical significance of this exploratory study was defined as p<0.10. Results: Seventy cases satisfied criteria for analysis. Median age was 59.5 years, mean tumor size was 1.8 cm (range 0.6-3.9 cm), 24% were grade 1, 66% grade 2 and 10% grade 3. Most tumors had high AR expression (median Allred score = 8, 97% had score ≥4). Median RS was 15 (range 1-53). AR expression showed a modest positive correlation with ER (R=0.37), but no correlation with PgR (R=0.09) or Ki67 (R=-0.18). In univariable analysis, AR (p=0.01), ER (p<0.001) and PgR (p<0.001) had significant negative associations with the RS. Ki67 had a non-significant positive association with RS (p=0.11 and p=0.16 for continuous and cut off analyses, respectively). Age (p=0.93), grade (p=0.40) and mitotic count (p=0.23) showed no association with RS. Multivariable analysis showed similar associations with RS (AR [p=0.07], ER [p=0.05], PgR [p=0.001]). Conclusions: AR is not associated with proliferative index (Ki67) but is associated with lower probability of disease recurrence (Low RS).
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