Abstract P5-03-05: Women with familial risk for breast cancer have an increased frequency of aldehyde dehydrogenase expressing cells in breast ductules

Abstract

Abstract Background Stem cell marker positive cells in cancers of various organs are associated with therapy resistance and adverse prognosis. Recently, the histology of benign breast tissue from cancer and non-cancer patients was assessed for cells that are positive for the putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH). The findings indicated an association between the expression of ALDH and patient hormonal factors that are suggested to increase the risk of breast cancer. The present study addressed possible associations between several risk factors for breast cancer, hormonal and genetic, and the cellular expression of ALDH in ductules of benign human breast tissue. Materials and methods The study included the following breast surgery patients: BRCA1/2 mutation carriers (n = 23), BRCA1/2 breast cancer patients (n = 28), sporadic breast cancer patients (n = 21), and non-cancer mammoplasty patients (n = 34). The patients were 20 to 81 years of age. A single, formalin fixed, paraffin-embedded tissue section of histologically benign tissue was selected from each, and was labelled with a monoclonal mouse anti-human antibody for ALDH (aa 7-128, N-term, diluted 1:100, Becton Dickinson and Comp. NJ, USA). Fifty or all available terminal duct lobular units were assessed for the presence of ALDH immunolabelled cells (median n = 45), for each ductular level (luminal–intermediate–basal). The distribution and frequency of ALDH immunolabeled cells were correlated to patient subgroups with different risk factors, using mammoplasty patients as a control group. Statistical analyses included linear and logistic regression, Spearman rank, Person test, and Fisher´s exact test. In two-tailed tests, p<0.05 was considered significant. Results There was a strong association between family history of breast cancer and a high frequency of ALDH+ cells (p = 0.001) at all ductular levels in all groups, regardless of BRCA status, age, number of childbirths, or occurrence of cancer. In pre-menopausal non-BRCA cancer patients, the frequency of ALDH+ cells increased with age, also after adjusting for family history and parity, for all ductular levels (p≤0.01). The frequency of ALDH+ cells decreased with the number of childbirths (p<0.03). BRCA1 mutation carriers exhibited a high frequency of ALDH+ cells in the non-basal ductular levels (p = 0.03), whereas BRCA2 cancer patients showed a high frequency of ALDH+ cells in the basal level (p = 0.02). Among post-menopausal patients, only on-going hormonal replacement therapy correlated with a high frequency of ALDH+ cells (p<0.03). No significant associations were found between the frequency of ALDH+ cells and the total duration of hormonal replacement therapy, or the use of contraceptive pill (ongoing or total), or age at menarche, or age at menopause. Conclusion In benign breast tissue, there is a positive association between the frequency of ductular ALDH+ cells and several hormonal and genetic breast cancer risk factors, particularly family history of breast cancer. This supports previous indications that ALDH plays a role in breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-03-05.