Clinical and pathological correlations in male breast cancer: Intratumoral aromatase expression via tissue microarray

Background: Male breast cancer (MBC) commonly expresses hormone receptors and there is anecdotal evidence of disease responsivity to aromatase inhibitors in the metastatic setting. Our objectives were to: (i) assess clinical-pathologic characteristics in a consecutive cohort of MBC (ii) evaluate intratumoral aromatase (ITA) expression via tissue microarray (TMA) and (iii) assess the prognostic impact of ITA Methods: A retrospective review was conducted to identify all cases of MBC seen at the Nova Scotia Cancer Center between 1985 and 2005. Specimens were reviewed for standard pathologic characteristics and tumor blocks were incorporated into three TMA's (four 1 mm cores per tumor). Immunohistochemistry (IHC) for ER, PR, Her2-neu and ITA was performed blinded to clinical outcomes. ITA staining intensity was compared to control, benign hepatic tissue and if greater than or equal to liver was scored positive and if less than liver was scored negative. The log-rank test was used for survival comparisons and Kaplan-Meyer curves were used to estimate 3- and 5-year progression-free and overall survival probabilities. Results: Fifty-four cases were identified with a median age of 64 (31-85 years). Median tumor size was 2.6 cm (0.3-8.0 cm) and 22(41%) had nodal metastases. Forty-five cases had tissue available for IHC. Of these, 40 (89%) were ER and 33 (73%) were PR positive. Her2-neu was overexpressed in four cases (10%) and 12 (27%) were positive for ITA expression. ITA positive tumors were less likely to be grade 3, have lymphovascular invasion or nodal metastases and were more likely to be of favorable histology compared to ITA negative tumors. In univariate analysis strong (versus weak) ITA expression was associated with improved 5 year overall (92% vs. 49%, P = 0.038) but not progression-free (82% vs. 76% P = 0.44) survival rates. Conclusions: Tumors with strong ITA expression may have a less aggressive phenotype compared to those with negative/weak ITA expression. Further investigation of ITA as a relevant prognostic factor as well as a potential therapeutic target in MBC is warranted.