A close association between alteration in growth kinetics by neoadjuvant chemotherapy and survival outcome in primary breast cancer

Int J Oncol. 2004 Aug;25(2):397-405.

Abstract

Few surrogate markers are available for predicting the survival benefit from chemotherapy in primary breast cancer. We examined tumor growth kinetics by assessing cytokeratin 18 neo-epitope (CK18NE), an apoptosis marker detected by M30 antibody and Ki-67 antigen, a proliferation marker detected by MIB-1 antibody in 72 primary breast cancer patients who underwent pre-operative anthracycline-based chemotherapy. Increase in M30 index and decrease in MIB-1 index after the exposure of 2 to 4 cycles of chemotherapy correlated significantly with pathological tumor response. Univariate survival analysis, conducted in the subgroup of 42 patients who underwent CAF (cyclophosphamide, adriamycin and 5-FU) therapy alone, showed that the patients with the high levels of M30 index (>35 counts/1000 tumor cells) and the low levels of MIB-1 index (<140 counts/1000 tumor cells) after chemotherapy had a remarkably favorable prognosis as compared with patients in other categories. In addition, the alteration in growth kinetics by the treatment showed a significant prognostic value. Multivariate analysis also confirmed that the post-treatment growth kinetics was an independent prognostic indicator. These findings suggest that the alteration in growth kinetics revealed by CK18NE and MIB-1 might be a surrogate marker for predicting the survival benefit from chemotherapy in primary breast cancer.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neoplasm / immunology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Keratins / analysis
  • Keratins / immunology
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / immunology
  • Kinetics
  • Middle Aged
  • Prognosis
  • Survival Analysis

Substances

  • Antibodies, Neoplasm
  • Ki-67 Antigen
  • Keratins
  • Doxorubicin
  • Cyclophosphamide
  • Fluorouracil