title: Evaluation of ER, PgR, HER-2, Ki-67, cyclin D1, and nm23-H1 as predictors of pathological complete response to neoadjuvant chemotherapy for locally advanced breast cancer.
abstract: The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with locally advanced breast cancer (LABC). Two hundred and twenty consecutive patients with LABC who had received neoadjuvant chemotherapy (NCT) with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre- and post-neoadjuvant chemotherapy (NCT) treatment expression levels and changes of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), cyclin D1, and nm23-H1 were detected by immunohistochemistry (IHC). The pCR rate was 9.1% (95% CI, 5.3-12.9%). In univariate analysis, poor tumor differentiation, OR after 2 cycles of NCT, both negative of ER/PgR, negative HER-2, positive cyclin D1, and positive nm23-H1 were found to be significantly predictive of a pCR. Histological grade and ER/PgR status were significant for pCR on multivariate analysis (P = 0.023 and 0.003, respectively). The expression levels of cyclin D1 (median, 8% vs. 9%; P = 0.016) after NCT treatment increased significantly, while the median Ki-67 proliferation index was dramatically decreased after NCT treatment from 35 to 15% (P = 0.036). However, after a Bonferroni adjustment, only the difference of Ki-67 proliferation index was still significant (P = 0.026). Histological grade and ER/PgR status are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in locally advanced breast cancer. Expression of HER-2, Ki-67, cyclin D1, and nm23-H1 were not predictive for pCR.
authors.affiliation: Division of Breast Surgery, Department of General Surgery, General Hospital of Chinese People's Liberation Army, No 28, Fuxing Rd, Beijing 100853, People's Republic of China. lixr301@163.com
authors.forename: Xi-ru
authors.initials: XR
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Jian-dong
authors.initials: JD
authors.lastname: Wang
authors.forename: Yi-qiong
authors.initials: YQ
authors.lastname: Zheng
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Ma
authors.forename: Xin
authors.initials: X
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D019938:Cyclin D1 / Q000097:blood; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000097:blood; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000097:blood; D020360:Neoadjuvant Therapy / Q000379:methods; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood; D011960:Receptors, Estrogen / Q000097:blood*; D011980:Receptors, Progesterone / Q000097:blood*; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019938:Cyclin D1; D000077143:Docetaxel; D015251:Epirubicin; D019394:Ki-67 Antigen; D054778:NM23 Nucleoside Diphosphate Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; C530104:CCND1 protein, human; C508053:ERBB2 protein, human; C517938:NME1 protein, human