title: Predictive Significance of p53, Ki-67, and Bcl-2 Expression for Pathologic Complete Response after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer.
abstract: OBJECTIVE
  Patients with triple-negative breast cancer (TNBC) with pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) have superior survival outcomes compared to those with residual disease after NAC. This study investigated the value of three biomarkers, p53, Ki-67, and Bcl-2 for predicting pCR in NAC-treated patients with TNBC.
  
  
  METHODS
  Between 2003 and 2012, 198 patients with pathologically confirmed primary TNBC were treated with two different taxane-based chemotherapeutic regimens prior to surgery. Before NAC, expression of p53 (cutoff 25%), Ki-67 (cutoff 10%), and Bcl-2 (cutoff 10%) was assessed immunohistochemically in core biopsy specimens. The incidence of pCR was correlated with the expression of these biomarkers.
  
  
  RESULTS
  Overall, pCR occurred in 37 of the 198 patients (18.7%). A significant association was observed between the pCR rate and overexpression of the p53 and Ki-67 biomarkers. Multivariate analysis showed that only p53 expression was independently associated with pCR to NAC (odds ratio, 3.961; p=0.003). The sensitivity, specificity, positive predictive value, and negative predictive value of p53 expression for predicting pCR were 77.8%, 50.3%, 26.2%, and 90.9%, respectively. The pCR rate was the lowest (5.2%) in patients with low expression of both p53 and Ki-67, and it was the highest (25.8%) when both biomarkers showed high expression.
  
  
  CONCLUSIONS
  Expression of p53 was significantly associated with pCR after NAC in patients with TNBC, suggesting that this biomarker might be particularly valuable in identifying TNBC patients prone to have residual disease after NAC.
authors.affiliation: Department of Surgery, Breast Cancer Center, Gachon University Gil Hospital, Incheon, Korea.
authors.forename: Taeryung
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Min Kyoon
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jun Woo
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jisun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Ahn
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Han-Byoel
authors.initials: HB
authors.lastname: Lee
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: In Ae
authors.initials: IA
authors.lastname: Park
authors.affiliation: Department of Surgery, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
keywords: Biological markers; Neoadjuvant therapy; Triple negative breast neoplasms; Tumor suppressor protein p53
references.citation: Biochem Biophys Res Commun. 1993 Apr 15;192(1):30-6
references.pmid: 8476431
references.citation: Eur J Cancer. 2006 Jul;42(10):1369-79
references.pmid: 16766179
references.citation: Int J Cancer. 2013 Mar 1;132(5):1227-31
references.pmid: 22886769
references.citation: Exp Ther Med. 2011 Mar;2(2):257-264
references.pmid: 22977494
references.citation: Breast Cancer Res. 2008;10(2):R30
references.pmid: 18380893
references.citation: Ann Oncol. 2003 Mar;14(3):428-32
references.pmid: 12598349
references.citation: Breast Cancer Res Treat. 2008 Sep;111(1):27-44
references.pmid: 17922188
references.citation: BMC Cancer. 2007 Feb 26;7:36
references.pmid: 17324279
references.citation: BMC Cancer. 2007 Nov 01;7:203
references.pmid: 17976237
references.citation: Am J Clin Oncol. 2006 Apr;29(2):171-7
references.pmid: 16601438
references.citation: Clin Cancer Res. 2007 Apr 15;13(8):2329-34
references.pmid: 17438091
references.citation: Med Oncol. 2009;26(3):344-9
references.pmid: 19016009
references.citation: Cancer Res. 1995 Jun 15;55(12):2487-9
references.pmid: 7780952
references.citation: J Clin Oncol. 2008 Mar 10;26(8):1275-81
references.pmid: 18250347
references.citation: Clin Cancer Res. 2000 Jul;6(7):2751-8
references.pmid: 10914720
references.citation: Br J Cancer. 1996 Jul;74(1):78-85
references.pmid: 8679463
references.citation: Ann Surg Oncol. 2009 May;16(5):1112-21
references.pmid: 19219507
references.citation: Ann Oncol. 2009 Jul;20(7):1193-8
references.pmid: 19221152
references.citation: Clin Cancer Res. 1995 Feb;1(2):189-98
references.pmid: 9815973
references.citation: Pathobiology. 2008;75(2):132-9
references.pmid: 18544968
references.citation: Breast Cancer Res. 2011 Mar 02;13(2):R22
references.pmid: 21366896
references.citation: Oncologist. 2008 Dec;13(12):1235-45
references.pmid: 19091781
references.citation: PLoS One. 2012;7(6):e39655
references.pmid: 22768103
references.citation: Clin Cancer Res. 2000 Jan;6(1):50-6
references.pmid: 10656431