title: Women with familial risk for breast cancer have an increased frequency of aldehyde dehydrogenase expressing cells in breast ductules.
abstract: BACKGROUND
  Knowledge is limited regarding the association between stem cells in histologically benign breast tissue and risk factors for breast cancer, and hence we addressed this issue in the present study. Recently, we assessed the histology of benign breast tissue from cancer and non-cancer patients for cells positive for the putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH), and the findings indicated an association between expression of ALDH and the hormonal factors menopause and hormone therapy. The current investigation examined possible associations between various known clinical and genetic risk factors for breast cancer and cellular expression of ALDH in ductules in benign human breast tissue.
  
  
  METHODS
  The study included breast surgery patients that were BRCA1/2 mutation carriers without breast cancer (n = 23), had BRCA1/2 (n = 28) or sporadic (n = 21) breast cancer, or required non-cancer-related mammoplasty (n = 34). The distribution and frequency of ALDH-immunolabelled cells were correlated to patient subgroups with different risk factors, using mammoplasty patients as a control group. Statistical analyses comprised linear and logistic regression, Spearman's rank test, Pearson's test, and Fisher's exact test. In two-tailed tests, p < 0.05 was considered significant.
  
  
  RESULTS
  A strong association was found 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, parity, or occurrence of cancer. In pre-menopausal non-BRCA cancer patients, the frequency of ALDH+ cells increased with age (p < 0.01) but decreased with increasing parity (p < 0.03). High frequencies of ALDH+ cells were found in the non-basal ductular levels in BRCA1 mutation carriers (p = 0.03), but in the basal ductular level in BRCA2 cancer patients (p = 0.02). Among post-menopausal patients, only on-going hormone replacement therapy was correlated with a high number of ALDH+ cells (p < 0.03).
  
  
  CONCLUSIONS
  In histologically normal breast tissue, we found a positive association between the frequency of ductular ALDH+ cells and several breast cancer risk factors, particularly family history of this disease, which supports previous evidence that ALDH plays a role in breast cancer.
authors.affiliation: Department of Oncology, Clinical Sciences Lund, Lund University, SE-221 85 Lund, Sweden. isfoss@mac.com.
authors.forename: Björn L
authors.initials: BL
authors.lastname: Isfoss
authors.forename: Bo
authors.initials: B
authors.lastname: Holmqvist
authors.forename: Helena
authors.initials: H
authors.lastname: Jernström
authors.forename: Per
authors.initials: P
authors.lastname: Alm
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson