Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer.
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.
Han
Wonshik
W
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. hanw@snu.ac.kr
Han
Mi-Ryung
MR
Kang
Jason Jongho
JJ
Bae
Ji-Yeon
JY
Lee
Ji Hyun
JH
Bae
Young Ju
YJ
Lee
Jeong Eon
JE
Shin
Hyuk-Jae
HJ
Hwang
Ki-Tae
KT
Hwang
Sung-Eun
SE
Kim
Sung-Won
SW
Noh
Dong-Young
DY
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*
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