title: Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer.
abstract: BACKGROUND
  A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer.
  
  
  METHODS
  We performed array comparative genomic hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 28 fresh-frozen ER-positive breast cancer tissues. All of the patients included had received at least 1 year of tamoxifen treatment. Nine patients had distant recurrence within 5 years (Recurrence group) of diagnosis and 19 patients were alive without disease at least 5 years after diagnosis (Non-recurrence group).
  
  
  RESULTS
  Potential prognostic variables were comparable between the two groups. In an unsupervised clustering analysis, samples from each group were well separated. The most common regions of gain in all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as called by CGH-Explorer software. The average frequency of copy number changes was similar between the two groups. The most significant chromosomal alterations found more often in the Recurrence group using two different statistical methods were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjusted p values < 0.001). In subgroup analysis according to lymph node status, loss of 11p15 and 1p36 were found more often in Recurrence group with borderline significance within the lymph node positive patients (adjusted p = 0.052).
  
  
  CONCLUSIONS
  Our array CGH analysis with BAC clones could detect various genomic alterations in ER-positive breast cancers, and Recurrence group samples showed a significantly different pattern of DNA copy number changes than did Non-recurrence group samples.
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. hanw@snu.ac.kr
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: Mi-Ryung
authors.initials: MR
authors.lastname: Han
authors.forename: Jason Jongho
authors.initials: JJ
authors.lastname: Kang
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Bae
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Bae
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.forename: Hyuk-Jae
authors.initials: HJ
authors.lastname: Shin
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Hwang
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Hwang
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000556:secondary / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D022202:Chromosomes, Artificial, Bacterial; D016000:Cluster Analysis; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D004967:Estrogens; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015993:Life Tables; D008408:Mastectomy; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004273:DNA, Neoplasm; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate