An expression signature of estrogen-regulated genes predicts disease-free survival in tamoxifen-treated patients better than progesterone receptor status.
We have used data derived from hormonal responses in human breast cancer cell lines to develop a panel of 36 genes which can robustly identify patients who will or will not benefit from tamoxifen treatment. These genes had the following characteristics: 1) induction by 17beta-estradiol (E2) in estrogen receptor (ER)-positive breast cancer cell lines in vitro, 2) under-expression in ER-negative breast tumors, and 3) correlation with PR mRNA expression in breast tumors. The average expression of these 36 genes was used as a "risk index" for assessing disease-specific survival in two independent tumor profile datasets of 60 and 67 patients treated with tamoxifen (these data not having been used to initially select the 36 genes), with a high risk group in each dataset defined as those with the bottom 25% of risk index values. This combined biological and informatic analysis is potentially applicable to many other cancer therapeutics.
Lippman
Marc E
ME
Division of Hematology Oncology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. mlippman@med.miami.edu
Rae
James M
JM
Chinnaiyan
Arul M
AM
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D018572:Disease-Free Survival; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics*; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol