Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists

J Clin Oncol. 2005 Apr 10;23(11):2477-92. doi: 10.1200/JCO.2005.07.559. Epub 2005 Mar 14.

Abstract

Purpose: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy.

Patients and methods: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment.

Results: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks.

Conclusion: These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anastrozole
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Cell Proliferation
  • Double-Blind Method
  • Female
  • Humans
  • Ki-67 Antigen / analysis*
  • Middle Aged
  • Neoadjuvant Therapy
  • Nitriles / administration & dosage
  • Nitriles / therapeutic use*
  • Postmenopause
  • Predictive Value of Tests
  • Receptor, ErbB-2 / analysis
  • Tamoxifen / administration & dosage
  • Tamoxifen / therapeutic use*
  • Treatment Outcome
  • Triazoles / administration & dosage
  • Triazoles / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Nitriles
  • Triazoles
  • Tamoxifen
  • Anastrozole
  • Receptor, ErbB-2