Tumor histological subtyping determined by hormone receptors and HER2 status defines different pathological complete response and outcome to dose-dense neoadjuvant chemotherapy in breast cancer patients

Clin Transl Oncol. 2014 Jun;16(6):548-54. doi: 10.1007/s12094-013-1116-z. Epub 2013 Oct 2.

Abstract

Purpose: To assess the impact in pathological complete response (pCR) and outcome of two dose-dense neoadjuvant chemotherapy (DDNC) regimens among different histological subtypes determined by hormonal receptor (HR) and HER2 status in breast cancer patients.

Methods: A total of 127 breast cancer patients were treated with DDNC in two prospective studies. A: adriamycin 40 mg/m(2) on day (d) 1 plus paclitaxel 150 mg/m(2) and gemcitabine 2,000 mg/m(2) on d2 for six cycles (n = 54). B: epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2) on d1 for three cycles, followed by paclitaxel 150 mg/m(2) and gemcitabine 2,500 mg/m(2) on d1 ± trastuzumab according to HER2 status (n = 73). Histological subtypes of breast cancer were 49 % HR+/HER2-, 17.5 % HR+/HER2+, 13.5 % HR-/HER2+ and 20 % HR-/HER2-.

Results: pCR (absence of invasive cells in breast and lymph node) was achieved in 35 patients (28 %). The pCR rate was significantly different between histological subtypes: HR+/HER2- (9 %), HR+/HER2+ (23 %), HR-/HER2+ (50 %), HR-/HER2- (56 %) (p < 0.001). The median follow-up was 81 months (r: 15-150 months). HR-/HER2- tumor subtype had a significantly worse DFS compared to HR+/HER2- (p = 0.02), RH+/HER2+ (p = 0.04) and HR-/HER2+ tumor subtypes (p = 0.02). HR-/HER2- tumor subtype had a significantly shorter OS compared to HR+/HER2- (p = 0.007), RH+/HER2+ (p = 0.05), and HR-/HER2+ (p = 0.03) tumor subtypes. However, no significant difference was observed in DFS and OS among HR-/HER2- tumors that achieved a pCR.

Conclusions: HR-/HER2- and HR-/HER2+ subtypes had a high pCR rate to DDNC. HR-/HER2- tumors had a worse outcome compared to other tumor subtypes but no significant difference was observed among HR-/HER2- tumors that achieved a pCR.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / pathology
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Doxorubicin / administration & dosage
  • Epirubicin / administration & dosage
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Remission Induction
  • Survival Rate
  • Trastuzumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Deoxycytidine
  • Epirubicin
  • Doxorubicin
  • Cyclophosphamide
  • Receptor, ErbB-2
  • Trastuzumab
  • Paclitaxel
  • Gemcitabine