Evaluation of ER and Ki-67 proliferation index as prognostic factors for survival following neoadjuvant chemotherapy with doxorubicin/docetaxel for locally advanced breast cancer

Cancer Chemother Pharmacol. 2008 Apr;61(4):569-77. doi: 10.1007/s00280-007-0506-8. Epub 2007 May 17.

Abstract

Background: The aim of the study was to identify reliable predictive biological markers for treatment outcome following neoadjuvant adriamycin/docetaxel (AT) chemotherapy in locally advanced breast cancer patients.

Materials and methods: This study was a phase II study on AT neoadjuvant chemotherapy in locally advanced breast cancer patients. Patients received 50 mg/m(2) of doxorubicin intravenously (IV) over 15 min followed by docetaxel 75 mg/m(2) infused over 1 h, repeated every 3 weeks for three cycles. Surgery was performed within 3-4 weeks following the last cycle of chemotherapy. We analyzed the pre-treatment and post-treatment expression levels of ER, PgR, HER-2, Ki-67 proliferation index, and p53 and examined the correlation between the markers and clinical parameters with treatment response, overall survival and relapse-free survival following neoadjuvant treatment.

Results: From July 2001 to September 2004, 61 patients were enrolled. The meaningful parameters adversely influencing survival were post-treatment ER(-) status (P = 0.013) and post-treatment Ki-67 index above 1.0% (P = 0.013). At the multivariate level, the post-treatment Ki-67 proliferation index < or = 1.0 was the only meaningful prognostic factor for better survival (P = 0.033). Notably, tumors with Ki-67 index < or = 1.0 were more likely to express ER with statistical significance (P = 0.002). Tumors with ER(+) and Ki-67 index < or = 1.0 showed the highest survival rate, followed by ER(+) and Ki-67 index > 1.0%, ER(-) and Ki-67 < or = 1.0%, and ER(-) and Ki-67 > 1.0% with the worst survival (P = 0.033).

Conclusion: Collectively, post-treatment ER status and Ki-67 proliferation index were prognostic of overall survival following neoadjuvant AT chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic / administration & dosage
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Disease-Free Survival
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Female
  • Genes, p53 / drug effects
  • Humans
  • Ki-67 Antigen / biosynthesis*
  • Middle Aged
  • Neoadjuvant Therapy*
  • Prognosis
  • Prospective Studies
  • Receptors, Estrogen / biosynthesis*
  • Receptors, Progesterone / biosynthesis
  • Receptors, Progesterone / drug effects
  • Survival Analysis
  • Taxoids / administration & dosage

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Biomarkers
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Taxoids
  • Docetaxel
  • Doxorubicin