Clinical and pathological predictors of the response to neoadjuvant anthracycline chemotherapy in locally advanced breast cancer

Med Oncol. 2006;23(2):171-83. doi: 10.1385/MO:23:2:171.

Abstract

Purpose: The aim of this study is to determine clinical and histopathological characteristics correlated to responsiveness to anthracycline-based neoadjuvant chemotherapy in breast cancer.

Patients and methods: We studied primary tumor specimens with local advanced breast cancer from 40 patients. Patients received anthracycline-based chemotherapy. Neoadjuvant regimen consisted in 600 mg/m2 5-fluorouracil, 60 mg/m2 doxorubicin, and 600 mg/m2 cyclophosphamide (FAC). The World Health Organization criteria were used to classify the tumors. We performed immunohistochemical staining for ER, PgR, HER-2, PCNA (proliferation cell nuclear antigen), Ki-67, p53, and Bcl-2. Clinical and histopathological characteristics were associated with clinical response and histopathological changes induced by chemotherapy.

Results: The mean age was 47 +/- 14 yr. Twenty-three percent of patients were in stage IIB and 77% were in stages IIIA and IIIB. Seven percent of patients had progression of the disease. Stable disease was observed in 42% of patients and 45% had partial response. Only 7% of patients had a complete response. Factors associated with a better and major percentage of clinical response were the administration of doxorubicin-based chemotherapy, administration of more than three cycles, clinical N1, atypia, more than 10 mitosis per high-power field, moderate to severe SBR grade, and a major index of cellular proliferation.

Conclusion: We found that tumors with large volumes, N2 node status, low cellular proliferation rate, positive immunoreactivity to p53, and low differentiation grade have a lower response to neoadjuvant chemotherapy with anthracycline. These patients could benefit from a different chemotherapy scheme to obtain a better control and resection.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Doxorubicin
  • Cyclophosphamide
  • Fluorouracil

Supplementary concepts

  • CAF protocol